Clinical depression
Overview
Major depressive disorder (MDD) (also known as recurrent depressive disorder, clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 accompanied by low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, and by loss of interest or pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in normally enjoyable activities. This cluster of symptoms (syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

) was named, described and classified as one of the mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s in the 1980 edition of the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's diagnostic manual
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

.
Encyclopedia
Major depressive disorder (MDD) (also known as recurrent depressive disorder, clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 accompanied by low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, and by loss of interest or pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in normally enjoyable activities. This cluster of symptoms (syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

) was named, described and classified as one of the mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s in the 1980 edition of the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's diagnostic manual
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

. The term "depression" is ambiguous. It is often used to denote this syndrome but may refer to other mood disorders or to lower mood states lacking clinical significance
Clinical significance
In medicine and psychology, clinical significance refers to either of two related but slightly dissimilar concepts whereby certain findings or differences, even if measurable or statistically confirmed, either may or may not have additional significance, either by being of a magnitude that conveys...

. Major depressive disorder is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, around 3.4% of people with major depression commit suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

, and up to 60% of people who committed suicide had depression or another mood disorder.
The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and a mental status examination
Mental status examination
The mental status examination in the USA or mental state examination in the rest of the world, abbreviated MSE, is an important part of the clinical assessment process in psychiatric practice...

. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. If depressive disorder is not detected in the early stages it may result in a slow recovery and affect or worsen the person's physical health
Health
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...

. Standardized screening tools such as Major Depression Inventory
Major Depression Inventory
The Major Depression Inventory is a self-report mood questionnaire developed by the World Health Organisation. The instrument was constructed by a team led by Professor Per Bech, a psychiatrist based at Frederiksborg General Hospital in Denmark...

 can be used to detect major depressive disorder. The most common time of onset is between the ages of 20 and 30 years, with a later peak between 30 and 40 years.
Typically, patients are treated with antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 medication and, in many cases, also receive psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

 or counseling, although the effectiveness of medication for mild or moderate cases is questionable. Hospitalization may be necessary in cases with associated self-neglect
Self-neglect
Self-neglect is a behavioural condition in which an individual neglects to attend to their basic needs, such as personal hygiene, appropriate clothing, feeding, or tending appropriately to any medical conditions they have. Extreme self-neglect can be known as Diogenes...

 or a significant risk of harm to self or others. A minority are treated with electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...

 (ECT), under a short-acting general anesthetic
General anaesthetic
A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia to facilitate surgery...

. The course of the disorder varies widely, from one episode lasting weeks to a lifelong disorder with recurrent major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

s. Depressed individuals have shorter life expectancies
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...

 than those without depression, in part because of greater susceptibility to medical illnesses and suicide. It is unclear whether or not medications affect the risk of suicide. Current and former patients may be stigmatized
Social stigma
Social stigma is the severe disapproval of or discontent with a person on the grounds of characteristics that distinguish them from other members of a society.Almost all stigma is based on a person differing from social or cultural norms...

.
The understanding of the nature and causes of depression has evolved over the centuries, though this understanding is incomplete and has left many aspects of depression as the subject of discussion and research. Proposed causes include psychological
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

, psycho-social, hereditary
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...

, evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

ary and biological
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

 factors. Certain types of long-term drug use can both cause and worsen depressive symptoms. Psychological treatments are based on theories of personality, interpersonal communication
Communication theory
Communication theory is a field of information and mathematics that studies the technical process of information and the human process of human communication.- History :- Origins :...

, and learning
Learning theory (education)
In psychology and education, learning is commonly defined as a process that brings together cognitive, emotional, and environmental influences and experiences for acquiring, enhancing, or making changes in one's knowledge, skills, values, and world views . Learning as a process focuses on what...

. Most biological theories focus on the monoamine
Monoamine neurotransmitter
thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...

 chemicals serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, which are naturally present in the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

 and assist communication between nerve cells
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

.

Symptoms and signs

Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health. Its impact on functioning and well-being has been equated to that of chronic medical conditions such as diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

.

A person having a major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

 usually exhibits a very low mood, which pervades all aspects of life, and an inability to experience pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in activities that were formerly enjoyed. Depressed people may be preoccupied with, or ruminate
Rumination (psychology)
Rumination is a way of responding to distress that involves repetitively focusing on the symptoms of distress, and on its possible causes and consequences. Rumination is more common in people who are pessimistic, neurotic, and who have negative attributional styles. The tendency to ruminate is a...

 over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred. In severe cases, depressed people may have symptoms of psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

. These symptoms include delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

s or, less commonly, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, usually unpleasant. Other symptoms of depression include poor concentration and memory (especially in those with melancholic or psychotic features), withdrawal from social situations and activities, reduced sex drive
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, and thoughts of death or suicide.

Insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

 is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep, but insomnia can also include difficulty falling asleep. Insomnia affects at least 80% of depressed people. Hypersomnia
Hypersomnia
Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent hypersomnia...

, or oversleeping, can also happen, affecting 15% of depressed people. Some antidepressants may also cause insomnia due to their stimulating effect.

A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization's
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 criteria for depression. Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur. Family and friends may notice that the person's behavior is either agitated
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

 or lethargic
Psychomotor retardation
Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...

.

In children

Although it is common for most children and teenagers to feel down or sad sometimes, a smaller number of youth experience a more severe phenomenon known as depression. Such young people, who are often described as "clinically" depressed, feel sad, hopeless, or irritable for weeks or even months at a time. They may lose interest in activities that they used to enjoy (e.g., playing with friends); their sleeping and eating habits often change (i.e., they may eat or sleep either more or less than usual); and they may have trouble thinking or paying attention, even to TV programs or games. Depressed children may often display an irritable mood rather than a depressed mood, and show varying symptoms depending on age and situation. Most lose interest in school and show a decline in academic performance. They may be described as clingy, demanding, dependent, or insecure. Diagnosis may be delayed or missed when symptoms are interpreted as normal moodiness. Depression may also coexist with attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

 (ADHD), complicating the diagnosis and treatment of both.

Of particular concern, youths who are clinically depressed may think or talk a lot about death and some depressed children have more specific thoughts about hurting or killing themselves. Often children and teenagers may have similar symptoms when they are grieving the loss of someone close to them. In clinical depression, however, these thoughts and feelings tend to appear even when the child has not experienced a loss or a sad event.

In the elderly

Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, and a more noticeable slowing of movements. Depression often coexists with physical disorders common among the elderly, such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, other cardiovascular diseases, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, and chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

.

Causes

The biopsychosocial model
Biopsychosocial model
The biopsychosocial model is a general model or approach that posits that biological, psychological , and social factors, all play a significant role in human functioning in the context of disease or illness...

 proposes that biological, psychological, and social factors all play a role in causing depression. The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

tic, implying an interaction between nature and nurture
Nature versus nurture
The nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...

, or schematic
Schema (psychology)
A schema , in psychology and cognitive science, describes any of several concepts including:* An organized pattern of thought or behavior.* A structured cluster of pre-conceived ideas....

, resulting from views of the world learned in childhood.

These interactive models have gained empirical
Empirical
The word empirical denotes information gained by means of observation or experimentation. Empirical data are data produced by an experiment or observation....

 support. For example, researchers in New Zealand took a prospective approach
Prospective cohort study
A prospective cohort study is a cohort study that follows over time a group of similar individuals who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome...

 to studying depression, by documenting over time
Longitudinal study
A longitudinal study is a correlational research study that involves repeated observations of the same variables over long periods of time — often many decades. It is a type of observational study. Longitudinal studies are often used in psychology to study developmental trends across the...

 how depression emerged among an initially normal
Normality (behavior)
In behavior, normal refers to a lack of significant deviation from the average. The phrase "not normal" is often applied in a negative sense Abnormality varies greatly in how pleasant or unpleasant this is for other people.The Oxford English Dictionary defines "normal" as "conforming to a standard"...

 cohort
Cohort (statistics)
In statistics and demography, a cohort is a group of subjects who have shared a particular time together during a particular time span . Cohorts may be tracked over extended periods in a cohort study. The cohort can be modified by censoring, i.e...

 of people. The researchers concluded that variation among the serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 (5-HTT) gene affects the chances
Moderation (statistics)
In statistics, moderation occurs when the relationship between two variables depends on a third variable. The third variable is referred to as the moderator variable or simply the moderator...

 that people who have dealt with very stressful life events will go on to experience depression. Specifically, depression may follow such events, but seems more likely to appear in people with one or two short allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

s of the 5-HTT gene. Additionally, a Swedish study estimated the heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...

 of depression—the degree to which individual differences in occurrence are associated with genetic differences—to be around 40% for women and 30% for men, and evolutionary psychologists
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...

 have proposed that the genetic basis for depression lies deep in the history of naturally selected
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

 adaptation
Adaptation
An adaptation in biology is a trait with a current functional role in the life history of an organism that is maintained and evolved by means of natural selection. An adaptation refers to both the current state of being adapted and to the dynamic evolutionary process that leads to the adaptation....

s. A substance-induced mood disorder resembling major depression has been causally linked to long-term drug use
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 or drug abuse
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...

, or to withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...

 from certain sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....

 and hypnotic drugs
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...

.

Monoamine hypothesis

Most antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 medications increase the levels of one or more of the monoamines—the neurotransmitters serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

—in the synaptic cleft
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...

 between neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s in the brain. Some medications affect the monoamine receptors directly.

Serotonin is hypothesized to regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways. According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter. Some antidepressants enhance the levels of norepinephrine directly, whereas others raise the levels of dopamine, a third monoamine neurotransmitter. These observations gave rise to the monoamine hypothesis of depression. In its contemporary formulation, the monoamine hypothesis postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." The proponents of this theory recommend the choice of an antidepressant with mechanism of action that impacts the most prominent symptoms. Anxious and irritable patients should be treated with SSRIs or norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...

s, and those experiencing a loss of energy and enjoyment of life with norepinephrine- and dopamine-enhancing drugs.

Besides the clinical observations that drugs which increase the amount of available monoamines are effective antidepressants, recent advances in psychiatric genetics
Psychiatric genetics
Psychiatric genetics, a subfield of behavioral neurogenetics, studies the role of genetics in psychological conditions such as alcoholism, schizophrenia, bipolar disorder, and autism. The basic principle behind psychiatric genetics is that genetic polymorphisms, as indicated by linkage to e.g...

 indicate that phenotypic variation in central monoamine function may be marginally associated with vulnerability to depression. Despite these findings, the cause of depression is not simply monoamine deficiency. In the past two decades, research has revealed multiple limitations of the monoamine hypothesis, and its explanatory inadequacy has been highlighted within the psychiatric community. A counterargument is that the mood-enhancing effect of MAO inhibitors and SSRIs takes weeks of treatment to develop, even though the boost in available monoamines occurs within hours. Another counterargument is based on experiments with pharmacological agents that cause depletion of monoamines; while deliberate reduction in the concentration of centrally available monoamines may slightly lower the mood of unmedicated depressed patients, this reduction does not affect the mood of healthy people. An intact monoamine system is necessary for antidepressants to achieve therapeutic effectiveness, but some medications like tianeptine
Tianeptine
Tianeptine was discovered by The French Society of Medical Research in the 1960s. Under the trade-names it is a drug used for treating major depressive episodes ....

 and opipramol
Opipramol
Opipramol is an antidepressant and anxiolytic used in Germany and other European countries. Although it is a member of the tricyclic antidepressants, opipramol's primary mechanism of action is much different in comparison...

 have antidepressant properties despite the fact that the former is a serotonin reuptake enhancer and the latter has no effect on the monoamine system. The monoamine hypothesis, already limited, has been further oversimplified when presented to the general public as a mass marketing tool, usually phrased as a "chemical imbalance
Chemical imbalance
Chemical imbalance is one hypothesis about the cause of mental illness. Other causes that are debated include psychological and social causes....

".

In 2003 a gene-environment interaction
Gene-environment interaction
Gene–environment interaction is the phenotypic effect of interactions between genes and the environment....

 (GxE) was hypothesized to explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR
5-HTTLPR
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...

); a 2009 meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 showed stressful life events were associated with depression, but found no evidence for an association with the 5-HTTLPR genotype. Another 2009 meta-analysis agreed with the latter finding. A 2010 review of studies in this area found a systematic relationship between the method used to assess environmental adversity and the results of the studies; this review also found that both 2009 meta-analyses were significantly biased toward negative studies, which used self-report measures of adversity.

Other theories

MRI scans of patients with depression have revealed a number of differences in brain structure compared to those who are not depressed. Recent meta-analyses of neuroimaging studies in major depression, reported that compared to controls, depressed patients had increased volume of the lateral ventricles
Lateral ventricles
The lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....

 and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

 and smaller volumes of the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...

, thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

, hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, and frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...

 (including the orbitofrontal cortex
Orbitofrontal cortex
The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making...

 and gyrus rectus
Gyrus rectus
The portion of the frontal lobe medial to the medial orbital gyrus is named the gyrus rectus , and is continuous with the superior frontal gyrus on the medial surface....

). Hyperintensities have been associated with patients with a late age of onset, and have led to the development of the theory of vascular depression
Subcortical ischemic depression
Subcortical ischemic depression, also known as vascular depression is a medical condition most commonly seen in elderly depressed patients. Late onset depression is increasingly seen as a distinct variety of depression, and is commonly detected with an MRI...

.

There may be a link between depression and neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...

 of the hippocampus, a center for both mood and memory. Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood. Drugs may increase serotonin levels in the brain, stimulating neurogenesis and thus increasing the total mass of the hippocampus. This increase may help to restore mood and memory. Similar relationships have been observed between depression and an area of the anterior cingulate cortex
Anterior cingulate cortex
The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...

 implicated in the modulation of emotional behavior. One of the neurotrophin
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...

s responsible for neurogenesis is brain-derived neurotrophic factor
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF...

 (BDNF). The level of BDNF in the blood plasma of depressed subjects is drastically reduced (more than threefold) as compared to the norm. Antidepressant treatment increases the blood level of BDNF. Although decreased plasma BDNF levels have been found in many other disorders, there is some evidence that BDNF is involved in the cause of depression and the mechanism of action of antidepressants.

There is some evidence that major depression may be caused in part by an overactive hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...

 (HPA axis) that results in an effect similar to the neuro-endocrine response to stress. Investigations reveal increased levels of the hormone cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 and enlarged pituitary and adrenal glands, suggesting disturbances of the endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...

 may play a role in some psychiatric disorders, including major depression. Oversecretion of corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

 from the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 is thought to drive this, and is implicated in the cognitive and arousal symptoms.

The hormone estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

 has been implicated in depressive disorders due to the increase in risk of depressive episodes after puberty, the antenatal period, and reduced rates after menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

. Conversely, the premenstrual and postpartum periods of low estrogen levels are also associated with increased risk. Sudden withdrawal of, fluctuations in or periods of sustained low levels of estrogen have been linked to significant mood lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized or restored.

Other research has explored potential roles of molecules necessary for overall cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 functioning: cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s. The symptoms of major depressive disorder are nearly identical to those of sickness behavior
Sickness behavior
thumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....

, the response of the body when the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 is fighting an infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

. This raises the possibility that depression can result from a maladaptive manifestation of sickness behavior as a result of abnormalities in circulating cytokines. The involvement of pro-inflammatory cytokines in depression is strongly suggested by a meta-analysis of the clinical literature showing higher blood concentrations of IL-6
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...

 and TNF-α in depressed subjects compared to controls. These immunological abnormalities may cause excessive prostaglandin E₂ production and likely excessive COX-2 expression. Abnormalities in how indoleamine 2,3-dioxygenase
Indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells...

 enyme activates as well as the metabolism of tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

-kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...

 may lead to excessive metabolism of tryptophan-kynurenine and lead to increased production of the neurotoxin quinolinic acid
Quinolinic acid
Quinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide.Quinolinic acid is a downstream kynurenine pathway metabolite of tryptophan...

, contributing to major depression. NMDA activation leading to excessive glutamatergic neurotransmission, may also contribute.

Finally, some relationships have been reported between specific subtypes of depression and climatic conditions. Thus, the incidence of psychotic depression has been found to increase when the barometric pressure is low, while the incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low.

Psychological

Various aspects of personality
Personality psychology
Personality psychology is a branch of psychology that studies personality and individual differences. Its areas of focus include:* Constructing a coherent picture of the individual and his or her major psychological processes...

 and its development
Personality Development
An individual's personality is an aggregate conglomeration of decisions we've made throughout our lives . There are inherent natural, genetic, and environmental factors that contribute to the development of our personality. According to process of socialization, "personality also colors our values,...

 appear to be integral to the occurrence and persistence of depression, with negative emotionality
Affect theory
In psychology, affect is an emotion or subjectively experienced feeling. Affect theory is a branch of psychoanalysis that attempts to organize affects into discrete categories and connect each one with its typical response. So, for example, the affect of joy is observed through the reaction of...

 as a common precursor. Although depressive episodes are strongly correlated with adverse events, a person's characteristic style of coping may be correlated with his or her resilience. Additionally, low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

 and self-defeating or distorted thinking are related to depression. Depression is less likely to occur, as well as quicker to remit, among those who are religious. It is not always clear which factors are causes or which are effects of depression; however, depressed persons who are able to reflect upon and challenge their thinking patterns often show improved mood and self-esteem.

American psychiatrist Aaron T. Beck
Aaron T. Beck
Aaron Temkin Beck is an American psychiatrist and a professor emeritus in the department of psychiatry at the University of Pennsylvania. He is widely regarded as the father of cognitive therapy, and his pioneering theories are widely used in the treatment of clinical depression...

, following on from the earlier work of George Kelly
George Kelly (psychologist)
George Kelly or George Kelley was an American psychologist, therapist and educator. He was best known for developing Personal Construct Psychology.- Biography :...

 and Albert Ellis, developed what is now known as a cognitive model of depression in the early 1960s. He proposed that three concepts underlie depression: a triad
Beck's cognitive triad
Beck's cognitive triad is a triad of types of negative thought present in depression proposed by Aaron Beck in 1976. The triad forms part of his Cognitive Theory Of Depression.The triad involves negative thoughts about:# The self...

 of negative thoughts composed of cognitive errors about oneself, one's world, and one's future; recurrent patterns of depressive thinking, or schemas; and distorted information processing. From these principles, he developed the structured technique of cognitive behavioral therapy (CBT). According to American psychologist Martin Seligman
Martin Seligman
Martin E. P. "Marty" Seligman is an American psychologist, educator, and author of self-help books. His theory of "learned helplessness" is widely respected among scientific psychologists....

, depression in humans is similar to learned helplessness
Learned helplessness
Learned helplessness, as a technical term in animal psychology and related human psychology, means a condition of a human person or an animal in which it has learned to behave helplessly, even when the opportunity is restored for it to help itself by avoiding an unpleasant or harmful circumstance...

 in laboratory animals, who remain in unpleasant situations when they are able to escape, but do not because they initially learned they had no control.
Attachment theory
Attachment theory
Attachment theory describes the dynamics of long-term relationships between humans. Its most important tenet is that an infant needs to develop a relationship with at least one primary caregiver for social and emotional development to occur normally. Attachment theory is an interdisciplinary study...

, which was developed by English psychiatrist John Bowlby
John Bowlby
Edward John Mostyn "John" Bowlby was a British psychologist, psychiatrist and psychoanalyst, notable for his interest in child development and for his pioneering work in attachment theory.- Family background :...

 in the 1960s, predicts a relationship between depressive disorder in adulthood and the quality of the earlier bond between the infant and their adult caregiver. In particular, it is thought that "the experiences of early loss, separation and rejection by the parent or caregiver (conveying the message that the child is unlovable) may all lead to insecure internal working models ... Internal cognitive representations of the self as unlovable and of attachment figures as unloving [or] untrustworthy would be consistent with parts of Beck’s cognitive triad". While a wide variety of studies has upheld the basic tenets of attachment theory, research has been inconclusive as to whether self-reported early attachment and later depression are demonstrably related.

Depressed individuals often blame themselves for negative events, and, as shown in a 1993 study of hospitalized adolescents with self-reported depression, those who blame themselves for negative occurrences may not take credit for positive outcomes. This tendency is characteristic of a depressive attributional
Attribution (psychology)
Attribution is a concept in social psychology referring to how individuals explain causes of behavior and events. Attribution theory is an umbrella term for various theories that attempt to explain these processes. Fritz Heider first proposed a theory of attribution The Psychology of Interpersonal...

, or pessimistic explanatory style
Explanatory style
Explanatory style is a psychological attribute that indicates how people explain to themselves why they experience a particular event, either positive or negative. Psychologists have identified three components in explanatory style:...

. According to Albert Bandura
Albert Bandura
Albert Bandura is a psychologist and the David Starr Jordan Professor Emeritus of Social Science in Psychology at Stanford University...

, a Canadian social psychologist associated with social cognitive theory
Social cognitive theory
Social cognitive theory, used in psychology, education, and communication, posits that portions of an individual's knowledge acquisition can be directly related to observing others within the context of social interactions, experiences, and outside media influences.-History:Social cognitive theory...

, depressed individuals have negative beliefs about themselves, based on experiences of failure, observing the failure of social models, a lack of social persuasion that they can succeed, and their own somatic and emotional states including tension and stress. These influences may result in a negative self-concept
Self-concept
Self-concept is a multi-dimensional construct that refers to an individual's perception of "self" in relation to any number of characteristics, such as academics , gender roles and sexuality, racial identity, and many others. Each of these characteristics is a research domain Self-concept (also...

 and a lack of self-efficacy
Self-efficacy
Self-efficacy is a term used in psychology, roughly corresponding to a person's belief in their own competence.It has been defined as the belief that one is capable of performing in a certain manner to attain certain set of goals. It is believed that our personalized ideas of self-efficacy affect...

; that is, they do not believe they can influence events or achieve personal goals.

An examination of depression in women indicates that vulnerability factors—such as early maternal loss, lack of a confiding relationship, responsibility for the care of several young children at home, and unemployment—can interact with life stressors to increase the risk of depression. For older adults, the factors are often health problems, changes in relationships with a spouse or adult children due to the transition to a care-giving
Caregiver
Caregiver may refer to:* Caregiver or carer - an unpaid person who cares for someone requiring support due to a disability, frailty, mental health problem, learning disability or old age...

 or care-needing role, the death of a significant other, or a change in the availability or quality of social relationships with older friends because of their own health-related life changes.

The understanding of depression has also received contributions from the psychoanalytic
Psychoanalysis
Psychoanalysis is a psychological theory developed in the late 19th and early 20th centuries by Austrian neurologist Sigmund Freud. Psychoanalysis has expanded, been criticized and developed in different directions, mostly by some of Freud's former students, such as Alfred Adler and Carl Gustav...

 and humanistic
Humanistic psychology
Humanistic psychology is a psychological perspective which rose to prominence in the mid-20th century, drawing on the work of early pioneers like Carl Rogers and the philosophies of existentialism and phenomenology...

 branches of psychology. From the classical psychoanalytic perspective of Austrian psychiatrist Sigmund Freud
Sigmund Freud
Sigmund Freud , born Sigismund Schlomo Freud , was an Austrian neurologist who founded the discipline of psychoanalysis...

, depression, or melancholia
Melancholia
Melancholia , also lugubriousness, from the Latin lugere, to mourn; moroseness, from the Latin morosus, self-willed, fastidious habit; wistfulness, from old English wist: intent, or saturnine, , in contemporary usage, is a mood disorder of non-specific depression,...

, may be related to interpersonal loss and early life experiences. Existential therapists
Existential therapy
Existential psychotherapy is a philosophical method of therapy that operates on the belief that inner conflict within a person is due to that individual's confrontation with the givens of existence. These givens, as noted by Irvin D...

 have connected depression to the lack of both meaning
Meaning (existential)
In existentialism, meaning is understood as the worth of life. Meaning in existentialism is unlike typical conceptions of "the meaning of life", because it is descriptive. Due to the method of existentialism, prescriptive or declarative statements about meaning are unjustified. Meaning is only...

 in the present and a vision of the future. The founder of humanistic psychology
Humanistic psychology
Humanistic psychology is a psychological perspective which rose to prominence in the mid-20th century, drawing on the work of early pioneers like Carl Rogers and the philosophies of existentialism and phenomenology...

, American psychologist Abraham Maslow
Abraham Maslow
Abraham Harold Maslow was an American professor of psychology at Brandeis University, Brooklyn College, New School for Social Research and Columbia University who created Maslow's hierarchy of needs...

, suggested that depression could arise when people are unable to attain their needs or to self-actualize (to realize their full potential).

Social

Poverty
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...

 and social isolation
Social isolation
Social isolation refers to a lack of contact with society for members of social species. There may be many causes and individuals in numerous generally social species are isolated at times, it need not be a pathological condition. In human society, in those cases where it is viewed as a pathology,...

 are associated with increased risk of mental health problems in general. Child abuse
Child abuse
Child abuse is the physical, sexual, emotional mistreatment, or neglect of a child. In the United States, the Centers for Disease Control and Prevention and the Department of Children And Families define child maltreatment as any act or series of acts of commission or omission by a parent or...

 (physical
Physical abuse
Physical abuse is abuse involving contact intended to cause feelings of intimidation, injury, or other physical suffering or bodily harm.-Forms of physical abuse:*Striking*Punching*Belting*Pushing, pulling*Slapping*Whipping*Striking with an object...

, emotional
Psychological abuse
Psychological abuse, also referred to as emotional abuse or mental abuse, is a form of abuse characterized by a person subjecting or exposing another to behavior that may result in psychological trauma, including anxiety, chronic depression, or post-traumatic stress disorder...

, sexual
Sexual abuse
Sexual abuse, also referred to as molestation, is the forcing of undesired sexual behavior by one person upon another. When that force is immediate, of short duration, or infrequent, it is called sexual assault. The offender is referred to as a sexual abuser or molester...

, or neglect) is also associated with increased risk of developing depressive disorders later in life. Such a link has good face validity given that it is during the years of development that a child is learning how to become a social being. Abuse of the child by the caregiver is bound to distort the developing personality and create a much greater risk for depression and many other debilitating mental and emotional states. Disturbances in family functioning, such as parental (particularly maternal) depression, severe marital conflict or divorce, death of a parent, or other disturbances in parenting are additional risk factors. In adulthood, stressful life events are strongly associated with the onset of major depressive episodes. In this context, life events connected to social rejection appear to be particularly related to depression. Evidence that a first episode of depression is more likely to be immediately preceded by stressful life events than are recurrent ones is consistent with the hypothesis that people may become increasingly sensitized to life stress over successive recurrences of depression.

The relationship between stressful life events and social support
Social support
Social support can be defined and measured in many ways. It can loosely be defined as feeling that one is cared for by and has assistance available from other people and that one is part of a supportive social network...

 has been a matter of some debate; the lack of social support may increase the likelihood that life stress will lead to depression, or the absence of social support may constitute a form of strain that leads to depression directly. There is evidence that neighborhood social disorder, for example, due to crime or illicit drugs, is a risk factor, and that a high neighborhood socioeconomic status, with better amenities, is a protective factor. Adverse conditions at work, particularly demanding jobs with little scope for decision-making, are associated with depression, although diversity and confounding factors make it difficult to confirm that the relationship is causal.

Evolutionary

From the standpoint of evolutionary theory, major depression is hypothesized, in some instances, to increase an individual's reproductive fitness
Fitness (biology)
Fitness is a central idea in evolutionary theory. It can be defined either with respect to a genotype or to a phenotype in a given environment...

. Evolutionary approaches to depression
Evolutionary approaches to depression
Evolutionary psychology has proposed several different evolutionary explanations for depression.- Background :Major depression is a leading cause of disability worldwide, and in 2000 was the fourth leading contributor to the global burden of disease ; it is also an important risk factor for suicide...

 and evolutionary psychology
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...

 posit specific mechanisms by which depression may have been genetically incorporated into the human gene pool, accounting for the high heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...

 and prevalence of depression by proposing that certain components of depression are adaptations, such as the behaviors relating to attachment
Attachment theory
Attachment theory describes the dynamics of long-term relationships between humans. Its most important tenet is that an infant needs to develop a relationship with at least one primary caregiver for social and emotional development to occur normally. Attachment theory is an interdisciplinary study...

 and social rank
Social class
Social classes are economic or cultural arrangements of groups in society. Class is an essential object of analysis for sociologists, political scientists, economists, anthropologists and social historians. In the social sciences, social class is often discussed in terms of 'social stratification'...

. Current behaviors can be explained as adaptations to regulate relationships or resources, although the result may be maladaptive in modern environments.

From another viewpoint, a counseling therapist may see depression not as a biochemical illness or disorder but as "a species-wide evolved suite of emotional programmes that are mostly activated by a perception, almost always over-negative, of a major decline in personal usefulness, that can sometimes be linked to guilt, shame or perceived rejection". This suite may have manifested in aging hunters in humans' foraging
Foraging
- Definitions and significance of foraging behavior :Foraging is the act of searching for and exploiting food resources. It affects an animal's fitness because it plays an important role in an animal's ability to survive and reproduce...

 past, who were marginalized by their declining skills, and may continue to appear in alienated members
Social alienation
The term social alienation has many discipline-specific uses; Roberts notes how even within the social sciences, it “is used to refer both to a personal psychological state and to a type of social relationship”...

 of today's society. The feelings of uselessness generated by such marginalization could hypothetically prompt support from friends and kin. Additionally, in a manner analogous to that in which physical pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 has evolved to hinder actions that may cause further injury, "psychic misery
Suffering
Suffering, or pain in a broad sense, is an individual's basic affective experience of unpleasantness and aversion associated with harm or threat of harm. Suffering may be qualified as physical or mental. It may come in all degrees of intensity, from mild to intolerable. Factors of duration and...

" may have evolved to prevent hasty and maladaptive reactions to distressing situations.

Drug and alcohol use

According to the DSM-IV, a diagnosis of mood disorder cannot be made if the cause is believed to be due to "the direct physiological effects of a substance"; when a syndrome resembling major depression is believed to be caused immediately by substance abuse or by an adverse drug reaction, it is referred to as, "substance-induced mood disturbance". Alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

 or excessive alcohol consumption significantly increases the risk of developing major depression. Like alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...

s are central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 depressant
Depressant
A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...

s; this class of medication is commonly used to treat insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, and muscular spasms. Similar to alcohol, benzodiazepines increase the risk of developing major depression. This increased risk may be due in part to the effects of drugs on neurochemistry
Neurochemistry
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...

, such as decreased levels of serotonin and norepinephrine. Chronic use of benzodiazepines also can cause or worsen depression, or depression may be part of a protracted withdrawal syndrome.

Clinical assessment

A diagnostic assessment may be conducted by a suitably trained general practitioner
General practitioner
A general practitioner is a medical practitioner who treats acute and chronic illnesses and provides preventive care and health education for all ages and both sexes. They have particular skills in treating people with multiple health issues and comorbidities...

, or by a psychiatrist
Psychiatrist
A psychiatrist is a physician who specializes in the diagnosis and treatment of mental disorders. All psychiatrists are trained in diagnostic evaluation and in psychotherapy...

 or psychologist
Psychologist
Psychologist is a professional or academic title used by individuals who are either:* Clinical professionals who work with patients in a variety of therapeutic contexts .* Scientists conducting psychological research or teaching psychology in a college...

, who records
Psychiatric history
A psychiatric history is the result of a medical process where a clinician working in the field of mental health systematically records the content of an interview with a patient...

 the person's current circumstances, biographical history, current symptoms and family history. The broad clinical aim is to formulate the relevant biological, psychological and social factors that may be impacting on the individual's mood. The assessor may also discuss the person's current ways of regulating their mood (healthy or otherwise) such as alcohol and drug use. The assessment also includes a mental state examination, which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or pessimism, self-harm
Self-harm
Self-harm or deliberate self-harm includes self-injury and self-poisoning and is defined as the intentional, direct injuring of body tissue most often done without suicidal intentions. These terms are used in the more recent literature in an attempt to reach a more neutral terminology...

 or suicide, and an absence of positive thoughts or plans. Specialist mental health services are rare in rural areas, and thus diagnosis and management is largely left to primary care
Primary care
Primary care is the term for the health services by providers who act as the principal point of consultation for patients within a health care system...

 clinicians. This issue is even more marked in developing countries. The score on a rating scale
Rating scale
A rating scale is a set of categories designed to elicit information about a quantitative or a qualitative attribute. In the social sciences, common examples are the Likert scale and 1-10 rating scales in which a person selects the number which is considered to reflect the perceived quality of a...

 alone is insufficient to diagnose depression to the satisfaction of the DSM or ICD, but it provides an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose. Screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

 programs have been advocated to improve detection of depression, but there is evidence that they do not improve detection rates, treatment, or outcome.

Primary care physician
Primary care physician
A primary care physician, or PCP, is a physician/medical doctor who provides both the first contact for a person with an undiagnosed health concern as well as continuing care of varied medical conditions, not limited by cause, organ system, or diagnosis....

s and other non-psychiatrist physicians have difficulty diagnosing depression, in part because they are trained to recognize and treat physical symptoms, and depression can cause a myriad of physical (psychosomatic) symptoms. Non-psychiatrists miss two-thirds of cases and unnecessarily treat other patients.

Before diagnosing a major depressive disorder, a doctor generally performs a medical examination and selected investigations to rule out other causes of symptoms. These include blood tests measuring TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 and thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 to exclude hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

; basic electrolytes and serum calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 to rule out a metabolic disturbance; and a full blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...

 including ESR
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...

 to rule out a systemic infection or chronic disease. Adverse affective reactions to medications or alcohol misuse are often ruled out, as well. Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 levels may be evaluated to diagnose hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...

, a cause of depression in men.

Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a dementing disorder
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

, such as Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

. Cognitive testing
Neuropsychological assessment
Neuropsychological assessment was traditionally carried out to assess the extent of impairment to a particular skill and to attempt to locate an area of the brain which may have been damaged after brain injury or neurological illness...

 and brain imaging can help distinguish depression from dementia. A CT scan
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. No biological tests confirm major depression. Investigations are not generally repeated for a subsequent episode unless there is a medical indication.

Biomarkers of depression have been sought to provide an objective method of diagnosis. There are several potential biomarkers, including Brain-Derived Neurotrophic Factor and various functional MRI techniques. One study developed a decision tree model of interpreting a series of fMRI scans taken during various activities. In their subjects, the authors of that study were able to achieve a sensitivity of 80% and a sensitivity of 87%, corresponding to a negative predictive value of 98% and a positive predictive value of 32% (positive and negative likelihood ratios were 6.15, 0.23 respectively). However, much more research is needed before these tests could be used clinically.

DSM-IV-TR and ICD-10 criteria

The most widely used criteria for diagnosing depressive conditions are found in the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

(DSM-IV-TR), and the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

's International Statistical Classification of Diseases and Related Health Problems
ICD
The International Statistical Classification of Diseases and Related Health Problems is a medical classification that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease...

(ICD-10) which uses the name recurrent depressive disorder. The latter system is typically used in European countries, while the former is used in the US and many other non-European nations, and the authors of both have worked towards conforming one with the other.

Both DSM-IV-TR and ICD-10 mark out typical (main) depressive symptoms. ICD-10 defines three typical depressive symptoms (depressed mood, anhedonia, and reduced energy), two of which should be present to determine depressive disorder diagnosis. According DSM-IV-TR there are two main depressive symptoms—depressed mood, anhedonia, at least one of which must be present to determine diagnosis of major depressive episode.

Major depressive disorder is classified as a mood disorder in DSM-IV-TR. The diagnosis hinges on the presence of single or recurrent major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

s. Further qualifiers are used to classify both the episode itself and the course of the disorder. The category Depressive Disorder Not Otherwise Specified is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode. The ICD-10
ICD-10
The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the...

 system does not use the term major depressive disorder, but lists very similar criteria for the diagnosis of a depressive episode (mild, moderate or severe); the term recurrent may be added if there have been multiple episodes without mania.

Major depressive episode

A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as psychotic depression
Psychotic depression
Psychotic major depression is a type of depression that can include symptoms and treatments that are different from those of non-psychotic major depressive disorder . PMD is estimated to affect about 0.4% of the population .PMD is sometimes "mistaken" for NPMD, schizoaffective disorder,...

—is automatically rated as severe. If the patient has had an episode of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

 or markedly elevated mood
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

, a diagnosis of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

 is made instead. Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole".

DSM-IV-TR excludes cases where the symptoms are a result of bereavement, although it is possible for normal bereavement to evolve into a depressive episode if the mood persists and the characteristic features of a major depressive episode develop. The criteria have been criticized because they do not take into account any other aspects of the personal and social context in which depression can occur. In addition, some studies have found little empirical support for the DSM-IV cut-off criteria, indicating they are a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration: Excluded are a range of related diagnoses, including dysthymia, which involves a chronic but milder mood disturbance; recurrent brief depression
Recurrent brief depression
Recurrent brief depression defines a mental disorder characterized by intermittent depressive episodes, in women not related to menstrual cycles, occurring at least once a month over at least one year or more fulfilling the diagnostic criteria for major depressive episodes except for duration...

, consisting of briefer depressive episodes; minor depressive disorder
Minor depressive disorder
Minor depressive Disorder, also known as Minor Depression, is a mood disorder that does not meet full criteria for Major depressive disorder but in which at least two depressive symptoms are present for two weeks. It is given in the DSM-IV-TR as an example of a Depressive Disorder Not Otherwise...

, whereby only some of the symptoms of major depression are present; and adjustment disorder with depressed mood
Adjustment disorder
Adjustment disorder is a psychological response to an identifiable stressor or group of stressors that cause significant emotional or behavioral symptoms that do not meet criteria for anxiety disorder, PTSD, or acute stress disorder...

, which denotes low mood resulting from a psychological response to an identifiable event or stressor.

Subtypes

The DSM-IV-TR recognizes five further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features:
  • Melancholic depression
    Melancholic depression
    Melancholic depression, or 'depression with melancholic features' is a subtype of major depression characterized by major depressive disorder with the following specific features: anhedonia , severe weight loss, psychomotor agitation or retardation, insomnia with early morning awakenings, guilt...

    is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief
    Grief
    Grief is a multi-faceted response to loss, particularly to the loss of someone or something to which a bond was formed. Although conventionally focused on the emotional response to loss, it also has physical, cognitive, behavioral, social, and philosophical dimensions...

     or loss, a worsening of symptoms in the morning hours, early morning waking, psychomotor retardation
    Psychomotor retardation
    Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...

    , excessive weight loss (not to be confused with anorexia nervosa
    Anorexia nervosa
    Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...

    ), or excessive guilt.
  • Atypical depression
    Atypical depression
    Atypical depression is a subtype of dysthymia and major depression, sharing many of the symptoms of both, but also being characterized by mood reactivity—being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot...

    is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain
    Weight gain
    Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...

     or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia
    Hypersomnia
    Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent hypersomnia...

    ), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection
    Social rejection
    Social rejection occurs when an individual is deliberately excluded from a social relationship or social interaction. The topic includes both interpersonal rejection and romantic rejection. A person can be rejected on an individual basis or by an entire group of people...

    .
  • Catatonic
    Catatonia
    Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....

     depression
    is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia
    Schizophrenia
    Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

     or in manic episodes, or may be caused by neuroleptic malignant syndrome
    Neuroleptic malignant syndrome
    Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...

    .
  • Postpartum depression
    Postpartum depression
    Postpartum depression , also called postnatal depression, is a form of clinical depression which can affect women, and less frequently men, typically after childbirth. Studies report prevalence rates among women from 5% to 25%, but methodological differences among the studies make the actual...

    , or mental and behavioural disorders associated with the puerperium, not elsewhere classified, refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression has an incidence rate of 10–15% among new mothers. The DSM-IV mandates that, in order to qualify as postpartum depression, onset occur within one month of delivery. It has been said that postpartum depression can last as long as three months.
  • Seasonal affective disorder
    Seasonal affective disorder
    Seasonal affective disorder , also known as winter depression, winter blues, summer depression, summer blues, or seasonal depression, is a mood disorder in which people who have normal mental health throughout most of the year experience depressive symptoms in the winter or summer, spring or autumn...

    (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.

Differential diagnoses

To confer major depressive disorder as the most likely diagnosis, other potential diagnoses
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 must be considered, including dysthymia, adjustment disorder with depressed mood or bipolar disorder. Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as double depression). Adjustment disorder with depressed mood
Adjustment disorder
Adjustment disorder is a psychological response to an identifiable stressor or group of stressors that cause significant emotional or behavioral symptoms that do not meet criteria for anxiety disorder, PTSD, or acute stress disorder...

 is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode. Bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

, also known as manic–depressive disorder, is a condition in which depressive phases alternate with periods of mania or hypomania
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

. Although depression is currently categorized as a separate disorder, there is ongoing debate because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a mood disorder continuum.

Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, medications, and substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...

. Depression due to physical illness is diagnosed as a mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

 due to a general medical condition. This condition is determined based on history, laboratory findings, or physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...

. When the depression is caused by a substance abused including a drug of abuse, a medication, or exposure to a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

, it is then diagnosed as a substance-induced mood disorder. In such cases, a substance is judged to be etiologically related to the mood disturbance.

Schizoaffective disorder
Schizoaffective disorder
Schizoaffective disorder is a psychiatric diagnosis that describes a mental disorder characterized by recurring episodes of elevated or depressed mood, or of simultaneously elevated and depressed mood, that alternate with, or occur together with, distortions in perception.Schizoaffective disorder...

 is different from major depressive disorder with psychotic features because in the schizoaffective disorder at least two weeks of delusions or hallucinations must occur in the absence of prominent mood symptoms.

Depressive symptoms may be identified during schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, delusional disorder
Delusional disorder
Delusional disorder is an uncommon psychiatric condition in which patients present with circumscribed symptoms of non-bizarre delusions, but with the absence of prominent hallucinations and no thought disorder, mood disorder, or significant flattening of affect...

, and psychotic disorder not otherwise specified, and in such cases those symptoms are considered associated features of these disorders, therefore, a separate diagnosis is not deemed necessary unless the depressive symptoms meet full criteria for a major depressive episode. In that case, a diagnosis of depressive disorder not otherwise specified may be made as well as a diagnosis of schizophrenia.

Some cognitive symptoms of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

 such as disorientation, apathy
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...

, difficulty concentrating and memory loss
Memory loss
Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...

 may get confused with a major depressive episode in major depressive disorder. They are especially difficult to determine in elderly patients. In such cases, the premorbid state of the patient may be helpful to differentiate both disorders. In the case of dementia, there tends to be a premorbid history of declining cognitive function. In the case of a major depressive disorder patients tend to exhibit a relatively normal premorbid state and abrupt cognitive decline associated with the depression.

Prevention

Behavioral interventions, such as interpersonal therapy, are effective at preventing new onset depression. Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet
Internet
The Internet is a global system of interconnected computer networks that use the standard Internet protocol suite to serve billions of users worldwide...

. However, an earlier meta-analysis found preventive programs with a competence-enhancing component to be superior to behaviorally oriented programs overall, and found behavioral programs to be particularly unhelpful for older people, for whom social support programs were uniquely beneficial. Additionally, the programs that best prevented depression comprised more than eight sessions, each lasting between 60 and 90 minutes, were provided by a combination of lay and professional workers, had a high-quality research design, reported attrition rates
Churn rate
Churn rate , in its broadest sense, is a measure of the number of individuals or items moving into or out of a collective over a specific period of time...

, and had a well-defined intervention. The "Coping with Depression" course (CWD) is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.

Management

The three most common treatments for depression are psychotherapy, medication, and electroconvulsive therapy.
Psychotherapy is the treatment of choice for people under 18, while electroconvulsive therapy is only used as a last resort. Care is usually given on an outpatient basis, while treatment in an inpatient unit is considered if there is a significant risk to self or others.

Treatment options are much more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition. Physical exercise
Physical exercise
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...

 is recommended for management of mild depression, but it has only a moderate, statistically insignificant effect on symptoms in most cases of major depressive disorder.
Major depressive disorder (MDD) (also known as recurrent depressive disorder, clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 accompanied by low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, and by loss of interest or pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in normally enjoyable activities. This cluster of symptoms (syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

) was named, described and classified as one of the mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s in the 1980 edition of the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's diagnostic manual
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

. The term "depression" is ambiguous. It is often used to denote this syndrome but may refer to other mood disorders or to lower mood states lacking clinical significance
Clinical significance
In medicine and psychology, clinical significance refers to either of two related but slightly dissimilar concepts whereby certain findings or differences, even if measurable or statistically confirmed, either may or may not have additional significance, either by being of a magnitude that conveys...

. Major depressive disorder is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, around 3.4% of people with major depression commit suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

, and up to 60% of people who committed suicide had depression or another mood disorder.


The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and a mental status examination
Mental status examination
The mental status examination in the USA or mental state examination in the rest of the world, abbreviated MSE, is an important part of the clinical assessment process in psychiatric practice...

. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. If depressive disorder is not detected in the early stages it may result in a slow recovery and affect or worsen the person's physical health
Health
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...

. Standardized screening tools such as Major Depression Inventory
Major Depression Inventory
The Major Depression Inventory is a self-report mood questionnaire developed by the World Health Organisation. The instrument was constructed by a team led by Professor Per Bech, a psychiatrist based at Frederiksborg General Hospital in Denmark...

 can be used to detect major depressive disorder. The most common time of onset is between the ages of 20 and 30 years, with a later peak between 30 and 40 years.


Typically, patients are treated with antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 medication and, in many cases, also receive psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

 or counseling, although the effectiveness of medication for mild or moderate cases is questionable. Hospitalization may be necessary in cases with associated self-neglect
Self-neglect
Self-neglect is a behavioural condition in which an individual neglects to attend to their basic needs, such as personal hygiene, appropriate clothing, feeding, or tending appropriately to any medical conditions they have. Extreme self-neglect can be known as Diogenes...

 or a significant risk of harm to self or others. A minority are treated with electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...

 (ECT), under a short-acting general anesthetic
General anaesthetic
A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia to facilitate surgery...

. The course of the disorder varies widely, from one episode lasting weeks to a lifelong disorder with recurrent major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

s. Depressed individuals have shorter life expectancies
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...

 than those without depression, in part because of greater susceptibility to medical illnesses and suicide. It is unclear whether or not medications affect the risk of suicide. Current and former patients may be stigmatized
Social stigma
Social stigma is the severe disapproval of or discontent with a person on the grounds of characteristics that distinguish them from other members of a society.Almost all stigma is based on a person differing from social or cultural norms...

.


The understanding of the nature and causes of depression has evolved over the centuries, though this understanding is incomplete and has left many aspects of depression as the subject of discussion and research. Proposed causes include psychological
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

, psycho-social, hereditary
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...

, evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

ary and biological
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

 factors. Certain types of long-term drug use can both cause and worsen depressive symptoms. Psychological treatments are based on theories of personality, interpersonal communication
Communication theory
Communication theory is a field of information and mathematics that studies the technical process of information and the human process of human communication.- History :- Origins :...

, and learning
Learning theory (education)
In psychology and education, learning is commonly defined as a process that brings together cognitive, emotional, and environmental influences and experiences for acquiring, enhancing, or making changes in one's knowledge, skills, values, and world views . Learning as a process focuses on what...

. Most biological theories focus on the monoamine
Monoamine neurotransmitter
thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...

 chemicals serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, which are naturally present in the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

 and assist communication between nerve cells
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

.

Symptoms and signs

Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health. Its impact on functioning and well-being has been equated to that of chronic medical conditions such as diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

.

A person having a major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

 usually exhibits a very low mood, which pervades all aspects of life, and an inability to experience pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in activities that were formerly enjoyed. Depressed people may be preoccupied with, or ruminate
Rumination (psychology)
Rumination is a way of responding to distress that involves repetitively focusing on the symptoms of distress, and on its possible causes and consequences. Rumination is more common in people who are pessimistic, neurotic, and who have negative attributional styles. The tendency to ruminate is a...

 over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred. In severe cases, depressed people may have symptoms of psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

. These symptoms include delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

s or, less commonly, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, usually unpleasant. Other symptoms of depression include poor concentration and memory (especially in those with melancholic or psychotic features), withdrawal from social situations and activities, reduced sex drive
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, and thoughts of death or suicide.

Insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

 is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep, but insomnia can also include difficulty falling asleep. Insomnia affects at least 80% of depressed people. Hypersomnia
Hypersomnia
Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent hypersomnia...

, or oversleeping, can also happen, affecting 15% of depressed people. Some antidepressants may also cause insomnia due to their stimulating effect.

A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization's
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 criteria for depression. Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur. Family and friends may notice that the person's behavior is either agitated
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

 or lethargic
Psychomotor retardation
Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...

.

In children

Although it is common for most children and teenagers to feel down or sad sometimes, a smaller number of youth experience a more severe phenomenon known as depression. Such young people, who are often described as "clinically" depressed, feel sad, hopeless, or irritable for weeks or even months at a time. They may lose interest in activities that they used to enjoy (e.g., playing with friends); their sleeping and eating habits often change (i.e., they may eat or sleep either more or less than usual); and they may have trouble thinking or paying attention, even to TV programs or games. Depressed children may often display an irritable mood rather than a depressed mood, and show varying symptoms depending on age and situation. Most lose interest in school and show a decline in academic performance. They may be described as clingy, demanding, dependent, or insecure. Diagnosis may be delayed or missed when symptoms are interpreted as normal moodiness. Depression may also coexist with attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

 (ADHD), complicating the diagnosis and treatment of both.

Of particular concern, youths who are clinically depressed may think or talk a lot about death and some depressed children have more specific thoughts about hurting or killing themselves. Often children and teenagers may have similar symptoms when they are grieving the loss of someone close to them. In clinical depression, however, these thoughts and feelings tend to appear even when the child has not experienced a loss or a sad event.

In the elderly

Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, and a more noticeable slowing of movements. Depression often coexists with physical disorders common among the elderly, such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, other cardiovascular diseases, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, and chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

.

Causes

The biopsychosocial model
Biopsychosocial model
The biopsychosocial model is a general model or approach that posits that biological, psychological , and social factors, all play a significant role in human functioning in the context of disease or illness...

 proposes that biological, psychological, and social factors all play a role in causing depression. The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

tic, implying an interaction between nature and nurture
Nature versus nurture
The nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...

, or schematic
Schema (psychology)
A schema , in psychology and cognitive science, describes any of several concepts including:* An organized pattern of thought or behavior.* A structured cluster of pre-conceived ideas....

, resulting from views of the world learned in childhood.

These interactive models have gained empirical
Empirical
The word empirical denotes information gained by means of observation or experimentation. Empirical data are data produced by an experiment or observation....

 support. For example, researchers in New Zealand took a prospective approach
Prospective cohort study
A prospective cohort study is a cohort study that follows over time a group of similar individuals who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome...

 to studying depression, by documenting over time
Longitudinal study
A longitudinal study is a correlational research study that involves repeated observations of the same variables over long periods of time — often many decades. It is a type of observational study. Longitudinal studies are often used in psychology to study developmental trends across the...

 how depression emerged among an initially normal
Normality (behavior)
In behavior, normal refers to a lack of significant deviation from the average. The phrase "not normal" is often applied in a negative sense Abnormality varies greatly in how pleasant or unpleasant this is for other people.The Oxford English Dictionary defines "normal" as "conforming to a standard"...

 cohort
Cohort (statistics)
In statistics and demography, a cohort is a group of subjects who have shared a particular time together during a particular time span . Cohorts may be tracked over extended periods in a cohort study. The cohort can be modified by censoring, i.e...

 of people. The researchers concluded that variation among the serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 (5-HTT) gene affects the chances
Moderation (statistics)
In statistics, moderation occurs when the relationship between two variables depends on a third variable. The third variable is referred to as the moderator variable or simply the moderator...

 that people who have dealt with very stressful life events will go on to experience depression. Specifically, depression may follow such events, but seems more likely to appear in people with one or two short allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

s of the 5-HTT gene. Additionally, a Swedish study estimated the heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...

 of depression—the degree to which individual differences in occurrence are associated with genetic differences—to be around 40% for women and 30% for men, and evolutionary psychologists
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...

 have proposed that the genetic basis for depression lies deep in the history of naturally selected
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

 adaptation
Adaptation
An adaptation in biology is a trait with a current functional role in the life history of an organism that is maintained and evolved by means of natural selection. An adaptation refers to both the current state of being adapted and to the dynamic evolutionary process that leads to the adaptation....

s. A substance-induced mood disorder resembling major depression has been causally linked to long-term drug use
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 or drug abuse
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...

, or to withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...

 from certain sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....

 and hypnotic drugs
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...

.

Monoamine hypothesis

Most antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 medications increase the levels of one or more of the monoamines—the neurotransmitters serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

—in the synaptic cleft
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...

 between neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s in the brain. Some medications affect the monoamine receptors directly.

Serotonin is hypothesized to regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways. According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter. Some antidepressants enhance the levels of norepinephrine directly, whereas others raise the levels of dopamine, a third monoamine neurotransmitter. These observations gave rise to the monoamine hypothesis of depression. In its contemporary formulation, the monoamine hypothesis postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." The proponents of this theory recommend the choice of an antidepressant with mechanism of action that impacts the most prominent symptoms. Anxious and irritable patients should be treated with SSRIs or norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...

s, and those experiencing a loss of energy and enjoyment of life with norepinephrine- and dopamine-enhancing drugs.

Besides the clinical observations that drugs which increase the amount of available monoamines are effective antidepressants, recent advances in psychiatric genetics
Psychiatric genetics
Psychiatric genetics, a subfield of behavioral neurogenetics, studies the role of genetics in psychological conditions such as alcoholism, schizophrenia, bipolar disorder, and autism. The basic principle behind psychiatric genetics is that genetic polymorphisms, as indicated by linkage to e.g...

 indicate that phenotypic variation in central monoamine function may be marginally associated with vulnerability to depression. Despite these findings, the cause of depression is not simply monoamine deficiency. In the past two decades, research has revealed multiple limitations of the monoamine hypothesis, and its explanatory inadequacy has been highlighted within the psychiatric community. A counterargument is that the mood-enhancing effect of MAO inhibitors and SSRIs takes weeks of treatment to develop, even though the boost in available monoamines occurs within hours. Another counterargument is based on experiments with pharmacological agents that cause depletion of monoamines; while deliberate reduction in the concentration of centrally available monoamines may slightly lower the mood of unmedicated depressed patients, this reduction does not affect the mood of healthy people. An intact monoamine system is necessary for antidepressants to achieve therapeutic effectiveness, but some medications like tianeptine
Tianeptine
Tianeptine was discovered by The French Society of Medical Research in the 1960s. Under the trade-names it is a drug used for treating major depressive episodes ....

 and opipramol
Opipramol
Opipramol is an antidepressant and anxiolytic used in Germany and other European countries. Although it is a member of the tricyclic antidepressants, opipramol's primary mechanism of action is much different in comparison...

 have antidepressant properties despite the fact that the former is a serotonin reuptake enhancer and the latter has no effect on the monoamine system. The monoamine hypothesis, already limited, has been further oversimplified when presented to the general public as a mass marketing tool, usually phrased as a "chemical imbalance
Chemical imbalance
Chemical imbalance is one hypothesis about the cause of mental illness. Other causes that are debated include psychological and social causes....

".

In 2003 a gene-environment interaction
Gene-environment interaction
Gene–environment interaction is the phenotypic effect of interactions between genes and the environment....

 (GxE) was hypothesized to explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR
5-HTTLPR
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...

); a 2009 meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 showed stressful life events were associated with depression, but found no evidence for an association with the 5-HTTLPR genotype. Another 2009 meta-analysis agreed with the latter finding. A 2010 review of studies in this area found a systematic relationship between the method used to assess environmental adversity and the results of the studies; this review also found that both 2009 meta-analyses were significantly biased toward negative studies, which used self-report measures of adversity.

Other theories

MRI scans of patients with depression have revealed a number of differences in brain structure compared to those who are not depressed. Recent meta-analyses of neuroimaging studies in major depression, reported that compared to controls, depressed patients had increased volume of the lateral ventricles
Lateral ventricles
The lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....

 and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

 and smaller volumes of the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...

, thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

, hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, and frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...

 (including the orbitofrontal cortex
Orbitofrontal cortex
The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making...

 and gyrus rectus
Gyrus rectus
The portion of the frontal lobe medial to the medial orbital gyrus is named the gyrus rectus , and is continuous with the superior frontal gyrus on the medial surface....

). Hyperintensities have been associated with patients with a late age of onset, and have led to the development of the theory of vascular depression
Subcortical ischemic depression
Subcortical ischemic depression, also known as vascular depression is a medical condition most commonly seen in elderly depressed patients. Late onset depression is increasingly seen as a distinct variety of depression, and is commonly detected with an MRI...

.

There may be a link between depression and neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...

 of the hippocampus, a center for both mood and memory. Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood. Drugs may increase serotonin levels in the brain, stimulating neurogenesis and thus increasing the total mass of the hippocampus. This increase may help to restore mood and memory. Similar relationships have been observed between depression and an area of the anterior cingulate cortex
Anterior cingulate cortex
The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...

 implicated in the modulation of emotional behavior. One of the neurotrophin
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...

s responsible for neurogenesis is brain-derived neurotrophic factor
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF...

 (BDNF). The level of BDNF in the blood plasma of depressed subjects is drastically reduced (more than threefold) as compared to the norm. Antidepressant treatment increases the blood level of BDNF. Although decreased plasma BDNF levels have been found in many other disorders, there is some evidence that BDNF is involved in the cause of depression and the mechanism of action of antidepressants.

There is some evidence that major depression may be caused in part by an overactive hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...

 (HPA axis) that results in an effect similar to the neuro-endocrine response to stress. Investigations reveal increased levels of the hormone cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 and enlarged pituitary and adrenal glands, suggesting disturbances of the endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...

 may play a role in some psychiatric disorders, including major depression. Oversecretion of corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

 from the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 is thought to drive this, and is implicated in the cognitive and arousal symptoms.

The hormone estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

 has been implicated in depressive disorders due to the increase in risk of depressive episodes after puberty, the antenatal period, and reduced rates after menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

. Conversely, the premenstrual and postpartum periods of low estrogen levels are also associated with increased risk. Sudden withdrawal of, fluctuations in or periods of sustained low levels of estrogen have been linked to significant mood lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized or restored.

Other research has explored potential roles of molecules necessary for overall cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 functioning: cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s. The symptoms of major depressive disorder are nearly identical to those of sickness behavior
Sickness behavior
thumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....

, the response of the body when the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 is fighting an infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

. This raises the possibility that depression can result from a maladaptive manifestation of sickness behavior as a result of abnormalities in circulating cytokines. The involvement of pro-inflammatory cytokines in depression is strongly suggested by a meta-analysis of the clinical literature showing higher blood concentrations of IL-6
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...

 and TNF-α in depressed subjects compared to controls. These immunological abnormalities may cause excessive prostaglandin E₂ production and likely excessive COX-2 expression. Abnormalities in how indoleamine 2,3-dioxygenase
Indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells...

 enyme activates as well as the metabolism of tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

-kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...

 may lead to excessive metabolism of tryptophan-kynurenine and lead to increased production of the neurotoxin quinolinic acid
Quinolinic acid
Quinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide.Quinolinic acid is a downstream kynurenine pathway metabolite of tryptophan...

, contributing to major depression. NMDA activation leading to excessive glutamatergic neurotransmission, may also contribute.

Finally, some relationships have been reported between specific subtypes of depression and climatic conditions. Thus, the incidence of psychotic depression has been found to increase when the barometric pressure is low, while the incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low.

Psychological

Various aspects of personality
Personality psychology
Personality psychology is a branch of psychology that studies personality and individual differences. Its areas of focus include:* Constructing a coherent picture of the individual and his or her major psychological processes...

 and its development
Personality Development
An individual's personality is an aggregate conglomeration of decisions we've made throughout our lives . There are inherent natural, genetic, and environmental factors that contribute to the development of our personality. According to process of socialization, "personality also colors our values,...

 appear to be integral to the occurrence and persistence of depression, with negative emotionality
Affect theory
In psychology, affect is an emotion or subjectively experienced feeling. Affect theory is a branch of psychoanalysis that attempts to organize affects into discrete categories and connect each one with its typical response. So, for example, the affect of joy is observed through the reaction of...

 as a common precursor. Although depressive episodes are strongly correlated with adverse events, a person's characteristic style of coping may be correlated with his or her resilience. Additionally, low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

 and self-defeating or distorted thinking are related to depression. Depression is less likely to occur, as well as quicker to remit, among those who are religious. It is not always clear which factors are causes or which are effects of depression; however, depressed persons who are able to reflect upon and challenge their thinking patterns often show improved mood and self-esteem.

American psychiatrist Aaron T. Beck
Aaron T. Beck
Aaron Temkin Beck is an American psychiatrist and a professor emeritus in the department of psychiatry at the University of Pennsylvania. He is widely regarded as the father of cognitive therapy, and his pioneering theories are widely used in the treatment of clinical depression...

, following on from the earlier work of George Kelly
George Kelly (psychologist)
George Kelly or George Kelley was an American psychologist, therapist and educator. He was best known for developing Personal Construct Psychology.- Biography :...

 and Albert Ellis, developed what is now known as a cognitive model of depression in the early 1960s. He proposed that three concepts underlie depression: a triad
Beck's cognitive triad
Beck's cognitive triad is a triad of types of negative thought present in depression proposed by Aaron Beck in 1976. The triad forms part of his Cognitive Theory Of Depression.The triad involves negative thoughts about:# The self...

 of negative thoughts composed of cognitive errors about oneself, one's world, and one's future; recurrent patterns of depressive thinking, or schemas; and distorted information processing. From these principles, he developed the structured technique of cognitive behavioral therapy (CBT). According to American psychologist Martin Seligman
Martin Seligman
Martin E. P. "Marty" Seligman is an American psychologist, educator, and author of self-help books. His theory of "learned helplessness" is widely respected among scientific psychologists....

, depression in humans is similar to learned helplessness
Learned helplessness
Learned helplessness, as a technical term in animal psychology and related human psychology, means a condition of a human person or an animal in which it has learned to behave helplessly, even when the opportunity is restored for it to help itself by avoiding an unpleasant or harmful circumstance...

 in laboratory animals, who remain in unpleasant situations when they are able to escape, but do not because they initially learned they had no control.


Attachment theory
Attachment theory
Attachment theory describes the dynamics of long-term relationships between humans. Its most important tenet is that an infant needs to develop a relationship with at least one primary caregiver for social and emotional development to occur normally. Attachment theory is an interdisciplinary study...

, which was developed by English psychiatrist John Bowlby
John Bowlby
Edward John Mostyn "John" Bowlby was a British psychologist, psychiatrist and psychoanalyst, notable for his interest in child development and for his pioneering work in attachment theory.- Family background :...

 in the 1960s, predicts a relationship between depressive disorder in adulthood and the quality of the earlier bond between the infant and their adult caregiver. In particular, it is thought that "the experiences of early loss, separation and rejection by the parent or caregiver (conveying the message that the child is unlovable) may all lead to insecure internal working models ... Internal cognitive representations of the self as unlovable and of attachment figures as unloving [or] untrustworthy would be consistent with parts of Beck’s cognitive triad". While a wide variety of studies has upheld the basic tenets of attachment theory, research has been inconclusive as to whether self-reported early attachment and later depression are demonstrably related.

Depressed individuals often blame themselves for negative events, and, as shown in a 1993 study of hospitalized adolescents with self-reported depression, those who blame themselves for negative occurrences may not take credit for positive outcomes. This tendency is characteristic of a depressive attributional
Attribution (psychology)
Attribution is a concept in social psychology referring to how individuals explain causes of behavior and events. Attribution theory is an umbrella term for various theories that attempt to explain these processes. Fritz Heider first proposed a theory of attribution The Psychology of Interpersonal...

, or pessimistic explanatory style
Explanatory style
Explanatory style is a psychological attribute that indicates how people explain to themselves why they experience a particular event, either positive or negative. Psychologists have identified three components in explanatory style:...

. According to Albert Bandura
Albert Bandura
Albert Bandura is a psychologist and the David Starr Jordan Professor Emeritus of Social Science in Psychology at Stanford University...

, a Canadian social psychologist associated with social cognitive theory
Social cognitive theory
Social cognitive theory, used in psychology, education, and communication, posits that portions of an individual's knowledge acquisition can be directly related to observing others within the context of social interactions, experiences, and outside media influences.-History:Social cognitive theory...

, depressed individuals have negative beliefs about themselves, based on experiences of failure, observing the failure of social models, a lack of social persuasion that they can succeed, and their own somatic and emotional states including tension and stress. These influences may result in a negative self-concept
Self-concept
Self-concept is a multi-dimensional construct that refers to an individual's perception of "self" in relation to any number of characteristics, such as academics , gender roles and sexuality, racial identity, and many others. Each of these characteristics is a research domain Self-concept (also...

 and a lack of self-efficacy
Self-efficacy
Self-efficacy is a term used in psychology, roughly corresponding to a person's belief in their own competence.It has been defined as the belief that one is capable of performing in a certain manner to attain certain set of goals. It is believed that our personalized ideas of self-efficacy affect...

; that is, they do not believe they can influence events or achieve personal goals.

An examination of depression in women indicates that vulnerability factors—such as early maternal loss, lack of a confiding relationship, responsibility for the care of several young children at home, and unemployment—can interact with life stressors to increase the risk of depression. For older adults, the factors are often health problems, changes in relationships with a spouse or adult children due to the transition to a care-giving
Caregiver
Caregiver may refer to:* Caregiver or carer - an unpaid person who cares for someone requiring support due to a disability, frailty, mental health problem, learning disability or old age...

 or care-needing role, the death of a significant other, or a change in the availability or quality of social relationships with older friends because of their own health-related life changes.

The understanding of depression has also received contributions from the psychoanalytic
Psychoanalysis
Psychoanalysis is a psychological theory developed in the late 19th and early 20th centuries by Austrian neurologist Sigmund Freud. Psychoanalysis has expanded, been criticized and developed in different directions, mostly by some of Freud's former students, such as Alfred Adler and Carl Gustav...

 and humanistic
Humanistic psychology
Humanistic psychology is a psychological perspective which rose to prominence in the mid-20th century, drawing on the work of early pioneers like Carl Rogers and the philosophies of existentialism and phenomenology...

 branches of psychology. From the classical psychoanalytic perspective of Austrian psychiatrist Sigmund Freud
Sigmund Freud
Sigmund Freud , born Sigismund Schlomo Freud , was an Austrian neurologist who founded the discipline of psychoanalysis...

, depression, or melancholia
Melancholia
Melancholia , also lugubriousness, from the Latin lugere, to mourn; moroseness, from the Latin morosus, self-willed, fastidious habit; wistfulness, from old English wist: intent, or saturnine, , in contemporary usage, is a mood disorder of non-specific depression,...

, may be related to interpersonal loss and early life experiences. Existential therapists
Existential therapy
Existential psychotherapy is a philosophical method of therapy that operates on the belief that inner conflict within a person is due to that individual's confrontation with the givens of existence. These givens, as noted by Irvin D...

 have connected depression to the lack of both meaning
Meaning (existential)
In existentialism, meaning is understood as the worth of life. Meaning in existentialism is unlike typical conceptions of "the meaning of life", because it is descriptive. Due to the method of existentialism, prescriptive or declarative statements about meaning are unjustified. Meaning is only...

 in the present and a vision of the future. The founder of humanistic psychology
Humanistic psychology
Humanistic psychology is a psychological perspective which rose to prominence in the mid-20th century, drawing on the work of early pioneers like Carl Rogers and the philosophies of existentialism and phenomenology...

, American psychologist Abraham Maslow
Abraham Maslow
Abraham Harold Maslow was an American professor of psychology at Brandeis University, Brooklyn College, New School for Social Research and Columbia University who created Maslow's hierarchy of needs...

, suggested that depression could arise when people are unable to attain their needs or to self-actualize (to realize their full potential).

Social


Poverty
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...

 and social isolation
Social isolation
Social isolation refers to a lack of contact with society for members of social species. There may be many causes and individuals in numerous generally social species are isolated at times, it need not be a pathological condition. In human society, in those cases where it is viewed as a pathology,...

 are associated with increased risk of mental health problems in general. Child abuse
Child abuse
Child abuse is the physical, sexual, emotional mistreatment, or neglect of a child. In the United States, the Centers for Disease Control and Prevention and the Department of Children And Families define child maltreatment as any act or series of acts of commission or omission by a parent or...

 (physical
Physical abuse
Physical abuse is abuse involving contact intended to cause feelings of intimidation, injury, or other physical suffering or bodily harm.-Forms of physical abuse:*Striking*Punching*Belting*Pushing, pulling*Slapping*Whipping*Striking with an object...

, emotional
Psychological abuse
Psychological abuse, also referred to as emotional abuse or mental abuse, is a form of abuse characterized by a person subjecting or exposing another to behavior that may result in psychological trauma, including anxiety, chronic depression, or post-traumatic stress disorder...

, sexual
Sexual abuse
Sexual abuse, also referred to as molestation, is the forcing of undesired sexual behavior by one person upon another. When that force is immediate, of short duration, or infrequent, it is called sexual assault. The offender is referred to as a sexual abuser or molester...

, or neglect) is also associated with increased risk of developing depressive disorders later in life. Such a link has good face validity given that it is during the years of development that a child is learning how to become a social being. Abuse of the child by the caregiver is bound to distort the developing personality and create a much greater risk for depression and many other debilitating mental and emotional states. Disturbances in family functioning, such as parental (particularly maternal) depression, severe marital conflict or divorce, death of a parent, or other disturbances in parenting are additional risk factors. In adulthood, stressful life events are strongly associated with the onset of major depressive episodes. In this context, life events connected to social rejection appear to be particularly related to depression. Evidence that a first episode of depression is more likely to be immediately preceded by stressful life events than are recurrent ones is consistent with the hypothesis that people may become increasingly sensitized to life stress over successive recurrences of depression.

The relationship between stressful life events and social support
Social support
Social support can be defined and measured in many ways. It can loosely be defined as feeling that one is cared for by and has assistance available from other people and that one is part of a supportive social network...

 has been a matter of some debate; the lack of social support may increase the likelihood that life stress will lead to depression, or the absence of social support may constitute a form of strain that leads to depression directly. There is evidence that neighborhood social disorder, for example, due to crime or illicit drugs, is a risk factor, and that a high neighborhood socioeconomic status, with better amenities, is a protective factor. Adverse conditions at work, particularly demanding jobs with little scope for decision-making, are associated with depression, although diversity and confounding factors make it difficult to confirm that the relationship is causal.

Evolutionary

From the standpoint of evolutionary theory, major depression is hypothesized, in some instances, to increase an individual's reproductive fitness
Fitness (biology)
Fitness is a central idea in evolutionary theory. It can be defined either with respect to a genotype or to a phenotype in a given environment...

. Evolutionary approaches to depression
Evolutionary approaches to depression
Evolutionary psychology has proposed several different evolutionary explanations for depression.- Background :Major depression is a leading cause of disability worldwide, and in 2000 was the fourth leading contributor to the global burden of disease ; it is also an important risk factor for suicide...

 and evolutionary psychology
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...

 posit specific mechanisms by which depression may have been genetically incorporated into the human gene pool, accounting for the high heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...

 and prevalence of depression by proposing that certain components of depression are adaptations, such as the behaviors relating to attachment
Attachment theory
Attachment theory describes the dynamics of long-term relationships between humans. Its most important tenet is that an infant needs to develop a relationship with at least one primary caregiver for social and emotional development to occur normally. Attachment theory is an interdisciplinary study...

 and social rank
Social class
Social classes are economic or cultural arrangements of groups in society. Class is an essential object of analysis for sociologists, political scientists, economists, anthropologists and social historians. In the social sciences, social class is often discussed in terms of 'social stratification'...

. Current behaviors can be explained as adaptations to regulate relationships or resources, although the result may be maladaptive in modern environments.

From another viewpoint, a counseling therapist may see depression not as a biochemical illness or disorder but as "a species-wide evolved suite of emotional programmes that are mostly activated by a perception, almost always over-negative, of a major decline in personal usefulness, that can sometimes be linked to guilt, shame or perceived rejection". This suite may have manifested in aging hunters in humans' foraging
Foraging
- Definitions and significance of foraging behavior :Foraging is the act of searching for and exploiting food resources. It affects an animal's fitness because it plays an important role in an animal's ability to survive and reproduce...

 past, who were marginalized by their declining skills, and may continue to appear in alienated members
Social alienation
The term social alienation has many discipline-specific uses; Roberts notes how even within the social sciences, it “is used to refer both to a personal psychological state and to a type of social relationship”...

 of today's society. The feelings of uselessness generated by such marginalization could hypothetically prompt support from friends and kin. Additionally, in a manner analogous to that in which physical pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 has evolved to hinder actions that may cause further injury, "psychic misery
Suffering
Suffering, or pain in a broad sense, is an individual's basic affective experience of unpleasantness and aversion associated with harm or threat of harm. Suffering may be qualified as physical or mental. It may come in all degrees of intensity, from mild to intolerable. Factors of duration and...

" may have evolved to prevent hasty and maladaptive reactions to distressing situations.

Drug and alcohol use

According to the DSM-IV, a diagnosis of mood disorder cannot be made if the cause is believed to be due to "the direct physiological effects of a substance"; when a syndrome resembling major depression is believed to be caused immediately by substance abuse or by an adverse drug reaction, it is referred to as, "substance-induced mood disturbance". Alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

 or excessive alcohol consumption significantly increases the risk of developing major depression. Like alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...

s are central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 depressant
Depressant
A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...

s; this class of medication is commonly used to treat insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, and muscular spasms. Similar to alcohol, benzodiazepines increase the risk of developing major depression. This increased risk may be due in part to the effects of drugs on neurochemistry
Neurochemistry
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...

, such as decreased levels of serotonin and norepinephrine. Chronic use of benzodiazepines also can cause or worsen depression, or depression may be part of a protracted withdrawal syndrome.

Clinical assessment

A diagnostic assessment may be conducted by a suitably trained general practitioner
General practitioner
A general practitioner is a medical practitioner who treats acute and chronic illnesses and provides preventive care and health education for all ages and both sexes. They have particular skills in treating people with multiple health issues and comorbidities...

, or by a psychiatrist
Psychiatrist
A psychiatrist is a physician who specializes in the diagnosis and treatment of mental disorders. All psychiatrists are trained in diagnostic evaluation and in psychotherapy...

 or psychologist
Psychologist
Psychologist is a professional or academic title used by individuals who are either:* Clinical professionals who work with patients in a variety of therapeutic contexts .* Scientists conducting psychological research or teaching psychology in a college...

, who records
Psychiatric history
A psychiatric history is the result of a medical process where a clinician working in the field of mental health systematically records the content of an interview with a patient...

 the person's current circumstances, biographical history, current symptoms and family history. The broad clinical aim is to formulate the relevant biological, psychological and social factors that may be impacting on the individual's mood. The assessor may also discuss the person's current ways of regulating their mood (healthy or otherwise) such as alcohol and drug use. The assessment also includes a mental state examination, which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or pessimism, self-harm
Self-harm
Self-harm or deliberate self-harm includes self-injury and self-poisoning and is defined as the intentional, direct injuring of body tissue most often done without suicidal intentions. These terms are used in the more recent literature in an attempt to reach a more neutral terminology...

 or suicide, and an absence of positive thoughts or plans. Specialist mental health services are rare in rural areas, and thus diagnosis and management is largely left to primary care
Primary care
Primary care is the term for the health services by providers who act as the principal point of consultation for patients within a health care system...

 clinicians. This issue is even more marked in developing countries. The score on a rating scale
Rating scale
A rating scale is a set of categories designed to elicit information about a quantitative or a qualitative attribute. In the social sciences, common examples are the Likert scale and 1-10 rating scales in which a person selects the number which is considered to reflect the perceived quality of a...

 alone is insufficient to diagnose depression to the satisfaction of the DSM or ICD, but it provides an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose. Screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

 programs have been advocated to improve detection of depression, but there is evidence that they do not improve detection rates, treatment, or outcome.

Primary care physician
Primary care physician
A primary care physician, or PCP, is a physician/medical doctor who provides both the first contact for a person with an undiagnosed health concern as well as continuing care of varied medical conditions, not limited by cause, organ system, or diagnosis....

s and other non-psychiatrist physicians have difficulty diagnosing depression, in part because they are trained to recognize and treat physical symptoms, and depression can cause a myriad of physical (psychosomatic) symptoms. Non-psychiatrists miss two-thirds of cases and unnecessarily treat other patients.

Before diagnosing a major depressive disorder, a doctor generally performs a medical examination and selected investigations to rule out other causes of symptoms. These include blood tests measuring TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 and thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 to exclude hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

; basic electrolytes and serum calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 to rule out a metabolic disturbance; and a full blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...

 including ESR
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...

 to rule out a systemic infection or chronic disease. Adverse affective reactions to medications or alcohol misuse are often ruled out, as well. Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 levels may be evaluated to diagnose hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...

, a cause of depression in men.

Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a dementing disorder
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

, such as Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

. Cognitive testing
Neuropsychological assessment
Neuropsychological assessment was traditionally carried out to assess the extent of impairment to a particular skill and to attempt to locate an area of the brain which may have been damaged after brain injury or neurological illness...

 and brain imaging can help distinguish depression from dementia. A CT scan
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. No biological tests confirm major depression. Investigations are not generally repeated for a subsequent episode unless there is a medical indication.

Biomarkers of depression have been sought to provide an objective method of diagnosis. There are several potential biomarkers, including Brain-Derived Neurotrophic Factor and various functional MRI techniques. One study developed a decision tree model of interpreting a series of fMRI scans taken during various activities. In their subjects, the authors of that study were able to achieve a sensitivity of 80% and a sensitivity of 87%, corresponding to a negative predictive value of 98% and a positive predictive value of 32% (positive and negative likelihood ratios were 6.15, 0.23 respectively). However, much more research is needed before these tests could be used clinically.

DSM-IV-TR and ICD-10 criteria

The most widely used criteria for diagnosing depressive conditions are found in the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

(DSM-IV-TR), and the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

's International Statistical Classification of Diseases and Related Health Problems
ICD
The International Statistical Classification of Diseases and Related Health Problems is a medical classification that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease...

(ICD-10) which uses the name recurrent depressive disorder. The latter system is typically used in European countries, while the former is used in the US and many other non-European nations, and the authors of both have worked towards conforming one with the other.

Both DSM-IV-TR and ICD-10 mark out typical (main) depressive symptoms. ICD-10 defines three typical depressive symptoms (depressed mood, anhedonia, and reduced energy), two of which should be present to determine depressive disorder diagnosis. According DSM-IV-TR there are two main depressive symptoms—depressed mood, anhedonia, at least one of which must be present to determine diagnosis of major depressive episode.

Major depressive disorder is classified as a mood disorder in DSM-IV-TR. The diagnosis hinges on the presence of single or recurrent major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

s. Further qualifiers are used to classify both the episode itself and the course of the disorder. The category Depressive Disorder Not Otherwise Specified is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode. The ICD-10
ICD-10
The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the...

 system does not use the term major depressive disorder, but lists very similar criteria for the diagnosis of a depressive episode (mild, moderate or severe); the term recurrent may be added if there have been multiple episodes without mania.

Major depressive episode

A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as psychotic depression
Psychotic depression
Psychotic major depression is a type of depression that can include symptoms and treatments that are different from those of non-psychotic major depressive disorder . PMD is estimated to affect about 0.4% of the population .PMD is sometimes "mistaken" for NPMD, schizoaffective disorder,...

—is automatically rated as severe. If the patient has had an episode of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

 or markedly elevated mood
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

, a diagnosis of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

 is made instead. Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole".

DSM-IV-TR excludes cases where the symptoms are a result of bereavement, although it is possible for normal bereavement to evolve into a depressive episode if the mood persists and the characteristic features of a major depressive episode develop. The criteria have been criticized because they do not take into account any other aspects of the personal and social context in which depression can occur. In addition, some studies have found little empirical support for the DSM-IV cut-off criteria, indicating they are a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration: Excluded are a range of related diagnoses, including dysthymia, which involves a chronic but milder mood disturbance; recurrent brief depression
Recurrent brief depression
Recurrent brief depression defines a mental disorder characterized by intermittent depressive episodes, in women not related to menstrual cycles, occurring at least once a month over at least one year or more fulfilling the diagnostic criteria for major depressive episodes except for duration...

, consisting of briefer depressive episodes; minor depressive disorder
Minor depressive disorder
Minor depressive Disorder, also known as Minor Depression, is a mood disorder that does not meet full criteria for Major depressive disorder but in which at least two depressive symptoms are present for two weeks. It is given in the DSM-IV-TR as an example of a Depressive Disorder Not Otherwise...

, whereby only some of the symptoms of major depression are present; and adjustment disorder with depressed mood
Adjustment disorder
Adjustment disorder is a psychological response to an identifiable stressor or group of stressors that cause significant emotional or behavioral symptoms that do not meet criteria for anxiety disorder, PTSD, or acute stress disorder...

, which denotes low mood resulting from a psychological response to an identifiable event or stressor.

Subtypes

The DSM-IV-TR recognizes five further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features:
  • Melancholic depression
    Melancholic depression
    Melancholic depression, or 'depression with melancholic features' is a subtype of major depression characterized by major depressive disorder with the following specific features: anhedonia , severe weight loss, psychomotor agitation or retardation, insomnia with early morning awakenings, guilt...

    is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief
    Grief
    Grief is a multi-faceted response to loss, particularly to the loss of someone or something to which a bond was formed. Although conventionally focused on the emotional response to loss, it also has physical, cognitive, behavioral, social, and philosophical dimensions...

     or loss, a worsening of symptoms in the morning hours, early morning waking, psychomotor retardation
    Psychomotor retardation
    Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...

    , excessive weight loss (not to be confused with anorexia nervosa
    Anorexia nervosa
    Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...

    ), or excessive guilt.
  • Atypical depression
    Atypical depression
    Atypical depression is a subtype of dysthymia and major depression, sharing many of the symptoms of both, but also being characterized by mood reactivity—being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot...

    is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain
    Weight gain
    Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...

     or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia
    Hypersomnia
    Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent hypersomnia...

    ), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection
    Social rejection
    Social rejection occurs when an individual is deliberately excluded from a social relationship or social interaction. The topic includes both interpersonal rejection and romantic rejection. A person can be rejected on an individual basis or by an entire group of people...

    .
  • Catatonic
    Catatonia
    Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....

     depression
    is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia
    Schizophrenia
    Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

     or in manic episodes, or may be caused by neuroleptic malignant syndrome
    Neuroleptic malignant syndrome
    Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...

    .
  • Postpartum depression
    Postpartum depression
    Postpartum depression , also called postnatal depression, is a form of clinical depression which can affect women, and less frequently men, typically after childbirth. Studies report prevalence rates among women from 5% to 25%, but methodological differences among the studies make the actual...

    , or mental and behavioural disorders associated with the puerperium, not elsewhere classified, refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression has an incidence rate of 10–15% among new mothers. The DSM-IV mandates that, in order to qualify as postpartum depression, onset occur within one month of delivery. It has been said that postpartum depression can last as long as three months.
  • Seasonal affective disorder
    Seasonal affective disorder
    Seasonal affective disorder , also known as winter depression, winter blues, summer depression, summer blues, or seasonal depression, is a mood disorder in which people who have normal mental health throughout most of the year experience depressive symptoms in the winter or summer, spring or autumn...

    (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.

Differential diagnoses

To confer major depressive disorder as the most likely diagnosis, other potential diagnoses
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 must be considered, including dysthymia, adjustment disorder with depressed mood or bipolar disorder. Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as double depression). Adjustment disorder with depressed mood
Adjustment disorder
Adjustment disorder is a psychological response to an identifiable stressor or group of stressors that cause significant emotional or behavioral symptoms that do not meet criteria for anxiety disorder, PTSD, or acute stress disorder...

 is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode. Bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

, also known as manic–depressive disorder, is a condition in which depressive phases alternate with periods of mania or hypomania
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

. Although depression is currently categorized as a separate disorder, there is ongoing debate because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a mood disorder continuum.

Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, medications, and substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...

. Depression due to physical illness is diagnosed as a mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

 due to a general medical condition. This condition is determined based on history, laboratory findings, or physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...

. When the depression is caused by a substance abused including a drug of abuse, a medication, or exposure to a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

, it is then diagnosed as a substance-induced mood disorder. In such cases, a substance is judged to be etiologically related to the mood disturbance.

Schizoaffective disorder
Schizoaffective disorder
Schizoaffective disorder is a psychiatric diagnosis that describes a mental disorder characterized by recurring episodes of elevated or depressed mood, or of simultaneously elevated and depressed mood, that alternate with, or occur together with, distortions in perception.Schizoaffective disorder...

 is different from major depressive disorder with psychotic features because in the schizoaffective disorder at least two weeks of delusions or hallucinations must occur in the absence of prominent mood symptoms.

Depressive symptoms may be identified during schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, delusional disorder
Delusional disorder
Delusional disorder is an uncommon psychiatric condition in which patients present with circumscribed symptoms of non-bizarre delusions, but with the absence of prominent hallucinations and no thought disorder, mood disorder, or significant flattening of affect...

, and psychotic disorder not otherwise specified, and in such cases those symptoms are considered associated features of these disorders, therefore, a separate diagnosis is not deemed necessary unless the depressive symptoms meet full criteria for a major depressive episode. In that case, a diagnosis of depressive disorder not otherwise specified may be made as well as a diagnosis of schizophrenia.

Some cognitive symptoms of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

 such as disorientation, apathy
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...

, difficulty concentrating and memory loss
Memory loss
Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...

 may get confused with a major depressive episode in major depressive disorder. They are especially difficult to determine in elderly patients. In such cases, the premorbid state of the patient may be helpful to differentiate both disorders. In the case of dementia, there tends to be a premorbid history of declining cognitive function. In the case of a major depressive disorder patients tend to exhibit a relatively normal premorbid state and abrupt cognitive decline associated with the depression.

Prevention

Behavioral interventions, such as interpersonal therapy, are effective at preventing new onset depression. Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet
Internet
The Internet is a global system of interconnected computer networks that use the standard Internet protocol suite to serve billions of users worldwide...

. However, an earlier meta-analysis found preventive programs with a competence-enhancing component to be superior to behaviorally oriented programs overall, and found behavioral programs to be particularly unhelpful for older people, for whom social support programs were uniquely beneficial. Additionally, the programs that best prevented depression comprised more than eight sessions, each lasting between 60 and 90 minutes, were provided by a combination of lay and professional workers, had a high-quality research design, reported attrition rates
Churn rate
Churn rate , in its broadest sense, is a measure of the number of individuals or items moving into or out of a collective over a specific period of time...

, and had a well-defined intervention. The "Coping with Depression" course (CWD) is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.

Management

The three most common treatments for depression are psychotherapy, medication, and electroconvulsive therapy.
Psychotherapy is the treatment of choice for people under 18, while electroconvulsive therapy is only used as a last resort. Care is usually given on an outpatient basis, while treatment in an inpatient unit is considered if there is a significant risk to self or others.

Treatment options are much more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition. Physical exercise
Physical exercise
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...

 is recommended for management of mild depression, but it has only a moderate, statistically insignificant effect on symptoms in most cases of major depressive disorder.
Major depressive disorder (MDD) (also known as recurrent depressive disorder, clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder characterized by an all-encompassing low mood
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

 accompanied by low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

, and by loss of interest or pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in normally enjoyable activities. This cluster of symptoms (syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

) was named, described and classified as one of the mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

s in the 1980 edition of the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's diagnostic manual
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

. The term "depression" is ambiguous. It is often used to denote this syndrome but may refer to other mood disorders or to lower mood states lacking clinical significance
Clinical significance
In medicine and psychology, clinical significance refers to either of two related but slightly dissimilar concepts whereby certain findings or differences, even if measurable or statistically confirmed, either may or may not have additional significance, either by being of a magnitude that conveys...

. Major depressive disorder is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, around 3.4% of people with major depression commit suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

, and up to 60% of people who committed suicide had depression or another mood disorder.


The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and a mental status examination
Mental status examination
The mental status examination in the USA or mental state examination in the rest of the world, abbreviated MSE, is an important part of the clinical assessment process in psychiatric practice...

. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. If depressive disorder is not detected in the early stages it may result in a slow recovery and affect or worsen the person's physical health
Health
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...

. Standardized screening tools such as Major Depression Inventory
Major Depression Inventory
The Major Depression Inventory is a self-report mood questionnaire developed by the World Health Organisation. The instrument was constructed by a team led by Professor Per Bech, a psychiatrist based at Frederiksborg General Hospital in Denmark...

 can be used to detect major depressive disorder. The most common time of onset is between the ages of 20 and 30 years, with a later peak between 30 and 40 years.


Typically, patients are treated with antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 medication and, in many cases, also receive psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

 or counseling, although the effectiveness of medication for mild or moderate cases is questionable. Hospitalization may be necessary in cases with associated self-neglect
Self-neglect
Self-neglect is a behavioural condition in which an individual neglects to attend to their basic needs, such as personal hygiene, appropriate clothing, feeding, or tending appropriately to any medical conditions they have. Extreme self-neglect can be known as Diogenes...

 or a significant risk of harm to self or others. A minority are treated with electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...

 (ECT), under a short-acting general anesthetic
General anaesthetic
A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia to facilitate surgery...

. The course of the disorder varies widely, from one episode lasting weeks to a lifelong disorder with recurrent major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

s. Depressed individuals have shorter life expectancies
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...

 than those without depression, in part because of greater susceptibility to medical illnesses and suicide. It is unclear whether or not medications affect the risk of suicide. Current and former patients may be stigmatized
Social stigma
Social stigma is the severe disapproval of or discontent with a person on the grounds of characteristics that distinguish them from other members of a society.Almost all stigma is based on a person differing from social or cultural norms...

.


The understanding of the nature and causes of depression has evolved over the centuries, though this understanding is incomplete and has left many aspects of depression as the subject of discussion and research. Proposed causes include psychological
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

, psycho-social, hereditary
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...

, evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

ary and biological
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

 factors. Certain types of long-term drug use can both cause and worsen depressive symptoms. Psychological treatments are based on theories of personality, interpersonal communication
Communication theory
Communication theory is a field of information and mathematics that studies the technical process of information and the human process of human communication.- History :- Origins :...

, and learning
Learning theory (education)
In psychology and education, learning is commonly defined as a process that brings together cognitive, emotional, and environmental influences and experiences for acquiring, enhancing, or making changes in one's knowledge, skills, values, and world views . Learning as a process focuses on what...

. Most biological theories focus on the monoamine
Monoamine neurotransmitter
thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...

 chemicals serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, which are naturally present in the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

 and assist communication between nerve cells
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

.

Symptoms and signs

Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health. Its impact on functioning and well-being has been equated to that of chronic medical conditions such as diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

.

A person having a major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

 usually exhibits a very low mood, which pervades all aspects of life, and an inability to experience pleasure
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....

 in activities that were formerly enjoyed. Depressed people may be preoccupied with, or ruminate
Rumination (psychology)
Rumination is a way of responding to distress that involves repetitively focusing on the symptoms of distress, and on its possible causes and consequences. Rumination is more common in people who are pessimistic, neurotic, and who have negative attributional styles. The tendency to ruminate is a...

 over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred. In severe cases, depressed people may have symptoms of psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

. These symptoms include delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

s or, less commonly, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, usually unpleasant. Other symptoms of depression include poor concentration and memory (especially in those with melancholic or psychotic features), withdrawal from social situations and activities, reduced sex drive
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...

, and thoughts of death or suicide.

Insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

 is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep, but insomnia can also include difficulty falling asleep. Insomnia affects at least 80% of depressed people. Hypersomnia
Hypersomnia
Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent hypersomnia...

, or oversleeping, can also happen, affecting 15% of depressed people. Some antidepressants may also cause insomnia due to their stimulating effect.

A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization's
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 criteria for depression. Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur. Family and friends may notice that the person's behavior is either agitated
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

 or lethargic
Psychomotor retardation
Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...

.

In children

Although it is common for most children and teenagers to feel down or sad sometimes, a smaller number of youth experience a more severe phenomenon known as depression. Such young people, who are often described as "clinically" depressed, feel sad, hopeless, or irritable for weeks or even months at a time. They may lose interest in activities that they used to enjoy (e.g., playing with friends); their sleeping and eating habits often change (i.e., they may eat or sleep either more or less than usual); and they may have trouble thinking or paying attention, even to TV programs or games. Depressed children may often display an irritable mood rather than a depressed mood, and show varying symptoms depending on age and situation. Most lose interest in school and show a decline in academic performance. They may be described as clingy, demanding, dependent, or insecure. Diagnosis may be delayed or missed when symptoms are interpreted as normal moodiness. Depression may also coexist with attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

 (ADHD), complicating the diagnosis and treatment of both.

Of particular concern, youths who are clinically depressed may think or talk a lot about death and some depressed children have more specific thoughts about hurting or killing themselves. Often children and teenagers may have similar symptoms when they are grieving the loss of someone close to them. In clinical depression, however, these thoughts and feelings tend to appear even when the child has not experienced a loss or a sad event.

In the elderly

Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, and a more noticeable slowing of movements. Depression often coexists with physical disorders common among the elderly, such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, other cardiovascular diseases, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, and chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

.

Causes

The biopsychosocial model
Biopsychosocial model
The biopsychosocial model is a general model or approach that posits that biological, psychological , and social factors, all play a significant role in human functioning in the context of disease or illness...

 proposes that biological, psychological, and social factors all play a role in causing depression. The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

tic, implying an interaction between nature and nurture
Nature versus nurture
The nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...

, or schematic
Schema (psychology)
A schema , in psychology and cognitive science, describes any of several concepts including:* An organized pattern of thought or behavior.* A structured cluster of pre-conceived ideas....

, resulting from views of the world learned in childhood.

These interactive models have gained empirical
Empirical
The word empirical denotes information gained by means of observation or experimentation. Empirical data are data produced by an experiment or observation....

 support. For example, researchers in New Zealand took a prospective approach
Prospective cohort study
A prospective cohort study is a cohort study that follows over time a group of similar individuals who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome...

 to studying depression, by documenting over time
Longitudinal study
A longitudinal study is a correlational research study that involves repeated observations of the same variables over long periods of time — often many decades. It is a type of observational study. Longitudinal studies are often used in psychology to study developmental trends across the...

 how depression emerged among an initially normal
Normality (behavior)
In behavior, normal refers to a lack of significant deviation from the average. The phrase "not normal" is often applied in a negative sense Abnormality varies greatly in how pleasant or unpleasant this is for other people.The Oxford English Dictionary defines "normal" as "conforming to a standard"...

 cohort
Cohort (statistics)
In statistics and demography, a cohort is a group of subjects who have shared a particular time together during a particular time span . Cohorts may be tracked over extended periods in a cohort study. The cohort can be modified by censoring, i.e...

 of people. The researchers concluded that variation among the serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

 (5-HTT) gene affects the chances
Moderation (statistics)
In statistics, moderation occurs when the relationship between two variables depends on a third variable. The third variable is referred to as the moderator variable or simply the moderator...

 that people who have dealt with very stressful life events will go on to experience depression. Specifically, depression may follow such events, but seems more likely to appear in people with one or two short allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

s of the 5-HTT gene. Additionally, a Swedish study estimated the heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...

 of depression—the degree to which individual differences in occurrence are associated with genetic differences—to be around 40% for women and 30% for men, and evolutionary psychologists
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...

 have proposed that the genetic basis for depression lies deep in the history of naturally selected
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

 adaptation
Adaptation
An adaptation in biology is a trait with a current functional role in the life history of an organism that is maintained and evolved by means of natural selection. An adaptation refers to both the current state of being adapted and to the dynamic evolutionary process that leads to the adaptation....

s. A substance-induced mood disorder resembling major depression has been causally linked to long-term drug use
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 or drug abuse
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...

, or to withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...

 from certain sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....

 and hypnotic drugs
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...

.

Monoamine hypothesis

Most antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 medications increase the levels of one or more of the monoamines—the neurotransmitters serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

—in the synaptic cleft
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...

 between neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s in the brain. Some medications affect the monoamine receptors directly.

Serotonin is hypothesized to regulate other neurotransmitter systems; decreased serotonin activity may allow these systems to act in unusual and erratic ways. According to this "permissive hypothesis", depression arises when low serotonin levels promote low levels of norepinephrine, another monoamine neurotransmitter. Some antidepressants enhance the levels of norepinephrine directly, whereas others raise the levels of dopamine, a third monoamine neurotransmitter. These observations gave rise to the monoamine hypothesis of depression. In its contemporary formulation, the monoamine hypothesis postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions, and compulsions; and dopamine to attention, motivation, pleasure, and reward, as well as interest in life." The proponents of this theory recommend the choice of an antidepressant with mechanism of action that impacts the most prominent symptoms. Anxious and irritable patients should be treated with SSRIs or norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...

s, and those experiencing a loss of energy and enjoyment of life with norepinephrine- and dopamine-enhancing drugs.

Besides the clinical observations that drugs which increase the amount of available monoamines are effective antidepressants, recent advances in psychiatric genetics
Psychiatric genetics
Psychiatric genetics, a subfield of behavioral neurogenetics, studies the role of genetics in psychological conditions such as alcoholism, schizophrenia, bipolar disorder, and autism. The basic principle behind psychiatric genetics is that genetic polymorphisms, as indicated by linkage to e.g...

 indicate that phenotypic variation in central monoamine function may be marginally associated with vulnerability to depression. Despite these findings, the cause of depression is not simply monoamine deficiency. In the past two decades, research has revealed multiple limitations of the monoamine hypothesis, and its explanatory inadequacy has been highlighted within the psychiatric community. A counterargument is that the mood-enhancing effect of MAO inhibitors and SSRIs takes weeks of treatment to develop, even though the boost in available monoamines occurs within hours. Another counterargument is based on experiments with pharmacological agents that cause depletion of monoamines; while deliberate reduction in the concentration of centrally available monoamines may slightly lower the mood of unmedicated depressed patients, this reduction does not affect the mood of healthy people. An intact monoamine system is necessary for antidepressants to achieve therapeutic effectiveness, but some medications like tianeptine
Tianeptine
Tianeptine was discovered by The French Society of Medical Research in the 1960s. Under the trade-names it is a drug used for treating major depressive episodes ....

 and opipramol
Opipramol
Opipramol is an antidepressant and anxiolytic used in Germany and other European countries. Although it is a member of the tricyclic antidepressants, opipramol's primary mechanism of action is much different in comparison...

 have antidepressant properties despite the fact that the former is a serotonin reuptake enhancer and the latter has no effect on the monoamine system. The monoamine hypothesis, already limited, has been further oversimplified when presented to the general public as a mass marketing tool, usually phrased as a "chemical imbalance
Chemical imbalance
Chemical imbalance is one hypothesis about the cause of mental illness. Other causes that are debated include psychological and social causes....

".

In 2003 a gene-environment interaction
Gene-environment interaction
Gene–environment interaction is the phenotypic effect of interactions between genes and the environment....

 (GxE) was hypothesized to explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR
5-HTTLPR
5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...

); a 2009 meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

 showed stressful life events were associated with depression, but found no evidence for an association with the 5-HTTLPR genotype. Another 2009 meta-analysis agreed with the latter finding. A 2010 review of studies in this area found a systematic relationship between the method used to assess environmental adversity and the results of the studies; this review also found that both 2009 meta-analyses were significantly biased toward negative studies, which used self-report measures of adversity.

Other theories

MRI scans of patients with depression have revealed a number of differences in brain structure compared to those who are not depressed. Recent meta-analyses of neuroimaging studies in major depression, reported that compared to controls, depressed patients had increased volume of the lateral ventricles
Lateral ventricles
The lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....

 and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

 and smaller volumes of the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...

, thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

, hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, and frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...

 (including the orbitofrontal cortex
Orbitofrontal cortex
The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making...

 and gyrus rectus
Gyrus rectus
The portion of the frontal lobe medial to the medial orbital gyrus is named the gyrus rectus , and is continuous with the superior frontal gyrus on the medial surface....

). Hyperintensities have been associated with patients with a late age of onset, and have led to the development of the theory of vascular depression
Subcortical ischemic depression
Subcortical ischemic depression, also known as vascular depression is a medical condition most commonly seen in elderly depressed patients. Late onset depression is increasingly seen as a distinct variety of depression, and is commonly detected with an MRI...

.

There may be a link between depression and neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...

 of the hippocampus, a center for both mood and memory. Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood. Drugs may increase serotonin levels in the brain, stimulating neurogenesis and thus increasing the total mass of the hippocampus. This increase may help to restore mood and memory. Similar relationships have been observed between depression and an area of the anterior cingulate cortex
Anterior cingulate cortex
The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...

 implicated in the modulation of emotional behavior. One of the neurotrophin
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...

s responsible for neurogenesis is brain-derived neurotrophic factor
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF...

 (BDNF). The level of BDNF in the blood plasma of depressed subjects is drastically reduced (more than threefold) as compared to the norm. Antidepressant treatment increases the blood level of BDNF. Although decreased plasma BDNF levels have been found in many other disorders, there is some evidence that BDNF is involved in the cause of depression and the mechanism of action of antidepressants.

There is some evidence that major depression may be caused in part by an overactive hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...

 (HPA axis) that results in an effect similar to the neuro-endocrine response to stress. Investigations reveal increased levels of the hormone cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

 and enlarged pituitary and adrenal glands, suggesting disturbances of the endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...

 may play a role in some psychiatric disorders, including major depression. Oversecretion of corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

 from the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 is thought to drive this, and is implicated in the cognitive and arousal symptoms.

The hormone estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

 has been implicated in depressive disorders due to the increase in risk of depressive episodes after puberty, the antenatal period, and reduced rates after menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

. Conversely, the premenstrual and postpartum periods of low estrogen levels are also associated with increased risk. Sudden withdrawal of, fluctuations in or periods of sustained low levels of estrogen have been linked to significant mood lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized or restored.

Other research has explored potential roles of molecules necessary for overall cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 functioning: cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s. The symptoms of major depressive disorder are nearly identical to those of sickness behavior
Sickness behavior
thumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....

, the response of the body when the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 is fighting an infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

. This raises the possibility that depression can result from a maladaptive manifestation of sickness behavior as a result of abnormalities in circulating cytokines. The involvement of pro-inflammatory cytokines in depression is strongly suggested by a meta-analysis of the clinical literature showing higher blood concentrations of IL-6
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...

 and TNF-α in depressed subjects compared to controls. These immunological abnormalities may cause excessive prostaglandin E₂ production and likely excessive COX-2 expression. Abnormalities in how indoleamine 2,3-dioxygenase
Indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase is an immunomodulatory enzyme produced by some alternatively activated macrophages and other immunoregulatory cells...

 enyme activates as well as the metabolism of tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

-kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...

 may lead to excessive metabolism of tryptophan-kynurenine and lead to increased production of the neurotoxin quinolinic acid
Quinolinic acid
Quinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide.Quinolinic acid is a downstream kynurenine pathway metabolite of tryptophan...

, contributing to major depression. NMDA activation leading to excessive glutamatergic neurotransmission, may also contribute.

Finally, some relationships have been reported between specific subtypes of depression and climatic conditions. Thus, the incidence of psychotic depression has been found to increase when the barometric pressure is low, while the incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low.

Psychological

Various aspects of personality
Personality psychology
Personality psychology is a branch of psychology that studies personality and individual differences. Its areas of focus include:* Constructing a coherent picture of the individual and his or her major psychological processes...

 and its development
Personality Development
An individual's personality is an aggregate conglomeration of decisions we've made throughout our lives . There are inherent natural, genetic, and environmental factors that contribute to the development of our personality. According to process of socialization, "personality also colors our values,...

 appear to be integral to the occurrence and persistence of depression, with negative emotionality
Affect theory
In psychology, affect is an emotion or subjectively experienced feeling. Affect theory is a branch of psychoanalysis that attempts to organize affects into discrete categories and connect each one with its typical response. So, for example, the affect of joy is observed through the reaction of...

 as a common precursor. Although depressive episodes are strongly correlated with adverse events, a person's characteristic style of coping may be correlated with his or her resilience. Additionally, low self-esteem
Self-esteem
Self-esteem is a term in psychology to reflect a person's overall evaluation or appraisal of his or her own worth. Self-esteem encompasses beliefs and emotions such as triumph, despair, pride and shame: some would distinguish how 'the self-concept is what we think about the self; self-esteem, the...

 and self-defeating or distorted thinking are related to depression. Depression is less likely to occur, as well as quicker to remit, among those who are religious. It is not always clear which factors are causes or which are effects of depression; however, depressed persons who are able to reflect upon and challenge their thinking patterns often show improved mood and self-esteem.

American psychiatrist Aaron T. Beck
Aaron T. Beck
Aaron Temkin Beck is an American psychiatrist and a professor emeritus in the department of psychiatry at the University of Pennsylvania. He is widely regarded as the father of cognitive therapy, and his pioneering theories are widely used in the treatment of clinical depression...

, following on from the earlier work of George Kelly
George Kelly (psychologist)
George Kelly or George Kelley was an American psychologist, therapist and educator. He was best known for developing Personal Construct Psychology.- Biography :...

 and Albert Ellis, developed what is now known as a cognitive model of depression in the early 1960s. He proposed that three concepts underlie depression: a triad
Beck's cognitive triad
Beck's cognitive triad is a triad of types of negative thought present in depression proposed by Aaron Beck in 1976. The triad forms part of his Cognitive Theory Of Depression.The triad involves negative thoughts about:# The self...

 of negative thoughts composed of cognitive errors about oneself, one's world, and one's future; recurrent patterns of depressive thinking, or schemas; and distorted information processing. From these principles, he developed the structured technique of cognitive behavioral therapy (CBT). According to American psychologist Martin Seligman
Martin Seligman
Martin E. P. "Marty" Seligman is an American psychologist, educator, and author of self-help books. His theory of "learned helplessness" is widely respected among scientific psychologists....

, depression in humans is similar to learned helplessness
Learned helplessness
Learned helplessness, as a technical term in animal psychology and related human psychology, means a condition of a human person or an animal in which it has learned to behave helplessly, even when the opportunity is restored for it to help itself by avoiding an unpleasant or harmful circumstance...

 in laboratory animals, who remain in unpleasant situations when they are able to escape, but do not because they initially learned they had no control.


Attachment theory
Attachment theory
Attachment theory describes the dynamics of long-term relationships between humans. Its most important tenet is that an infant needs to develop a relationship with at least one primary caregiver for social and emotional development to occur normally. Attachment theory is an interdisciplinary study...

, which was developed by English psychiatrist John Bowlby
John Bowlby
Edward John Mostyn "John" Bowlby was a British psychologist, psychiatrist and psychoanalyst, notable for his interest in child development and for his pioneering work in attachment theory.- Family background :...

 in the 1960s, predicts a relationship between depressive disorder in adulthood and the quality of the earlier bond between the infant and their adult caregiver. In particular, it is thought that "the experiences of early loss, separation and rejection by the parent or caregiver (conveying the message that the child is unlovable) may all lead to insecure internal working models ... Internal cognitive representations of the self as unlovable and of attachment figures as unloving [or] untrustworthy would be consistent with parts of Beck’s cognitive triad". While a wide variety of studies has upheld the basic tenets of attachment theory, research has been inconclusive as to whether self-reported early attachment and later depression are demonstrably related.

Depressed individuals often blame themselves for negative events, and, as shown in a 1993 study of hospitalized adolescents with self-reported depression, those who blame themselves for negative occurrences may not take credit for positive outcomes. This tendency is characteristic of a depressive attributional
Attribution (psychology)
Attribution is a concept in social psychology referring to how individuals explain causes of behavior and events. Attribution theory is an umbrella term for various theories that attempt to explain these processes. Fritz Heider first proposed a theory of attribution The Psychology of Interpersonal...

, or pessimistic explanatory style
Explanatory style
Explanatory style is a psychological attribute that indicates how people explain to themselves why they experience a particular event, either positive or negative. Psychologists have identified three components in explanatory style:...

. According to Albert Bandura
Albert Bandura
Albert Bandura is a psychologist and the David Starr Jordan Professor Emeritus of Social Science in Psychology at Stanford University...

, a Canadian social psychologist associated with social cognitive theory
Social cognitive theory
Social cognitive theory, used in psychology, education, and communication, posits that portions of an individual's knowledge acquisition can be directly related to observing others within the context of social interactions, experiences, and outside media influences.-History:Social cognitive theory...

, depressed individuals have negative beliefs about themselves, based on experiences of failure, observing the failure of social models, a lack of social persuasion that they can succeed, and their own somatic and emotional states including tension and stress. These influences may result in a negative self-concept
Self-concept
Self-concept is a multi-dimensional construct that refers to an individual's perception of "self" in relation to any number of characteristics, such as academics , gender roles and sexuality, racial identity, and many others. Each of these characteristics is a research domain Self-concept (also...

 and a lack of self-efficacy
Self-efficacy
Self-efficacy is a term used in psychology, roughly corresponding to a person's belief in their own competence.It has been defined as the belief that one is capable of performing in a certain manner to attain certain set of goals. It is believed that our personalized ideas of self-efficacy affect...

; that is, they do not believe they can influence events or achieve personal goals.

An examination of depression in women indicates that vulnerability factors—such as early maternal loss, lack of a confiding relationship, responsibility for the care of several young children at home, and unemployment—can interact with life stressors to increase the risk of depression. For older adults, the factors are often health problems, changes in relationships with a spouse or adult children due to the transition to a care-giving
Caregiver
Caregiver may refer to:* Caregiver or carer - an unpaid person who cares for someone requiring support due to a disability, frailty, mental health problem, learning disability or old age...

 or care-needing role, the death of a significant other, or a change in the availability or quality of social relationships with older friends because of their own health-related life changes.

The understanding of depression has also received contributions from the psychoanalytic
Psychoanalysis
Psychoanalysis is a psychological theory developed in the late 19th and early 20th centuries by Austrian neurologist Sigmund Freud. Psychoanalysis has expanded, been criticized and developed in different directions, mostly by some of Freud's former students, such as Alfred Adler and Carl Gustav...

 and humanistic
Humanistic psychology
Humanistic psychology is a psychological perspective which rose to prominence in the mid-20th century, drawing on the work of early pioneers like Carl Rogers and the philosophies of existentialism and phenomenology...

 branches of psychology. From the classical psychoanalytic perspective of Austrian psychiatrist Sigmund Freud
Sigmund Freud
Sigmund Freud , born Sigismund Schlomo Freud , was an Austrian neurologist who founded the discipline of psychoanalysis...

, depression, or melancholia
Melancholia
Melancholia , also lugubriousness, from the Latin lugere, to mourn; moroseness, from the Latin morosus, self-willed, fastidious habit; wistfulness, from old English wist: intent, or saturnine, , in contemporary usage, is a mood disorder of non-specific depression,...

, may be related to interpersonal loss and early life experiences. Existential therapists
Existential therapy
Existential psychotherapy is a philosophical method of therapy that operates on the belief that inner conflict within a person is due to that individual's confrontation with the givens of existence. These givens, as noted by Irvin D...

 have connected depression to the lack of both meaning
Meaning (existential)
In existentialism, meaning is understood as the worth of life. Meaning in existentialism is unlike typical conceptions of "the meaning of life", because it is descriptive. Due to the method of existentialism, prescriptive or declarative statements about meaning are unjustified. Meaning is only...

 in the present and a vision of the future. The founder of humanistic psychology
Humanistic psychology
Humanistic psychology is a psychological perspective which rose to prominence in the mid-20th century, drawing on the work of early pioneers like Carl Rogers and the philosophies of existentialism and phenomenology...

, American psychologist Abraham Maslow
Abraham Maslow
Abraham Harold Maslow was an American professor of psychology at Brandeis University, Brooklyn College, New School for Social Research and Columbia University who created Maslow's hierarchy of needs...

, suggested that depression could arise when people are unable to attain their needs or to self-actualize (to realize their full potential).

Social


Poverty
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...

 and social isolation
Social isolation
Social isolation refers to a lack of contact with society for members of social species. There may be many causes and individuals in numerous generally social species are isolated at times, it need not be a pathological condition. In human society, in those cases where it is viewed as a pathology,...

 are associated with increased risk of mental health problems in general. Child abuse
Child abuse
Child abuse is the physical, sexual, emotional mistreatment, or neglect of a child. In the United States, the Centers for Disease Control and Prevention and the Department of Children And Families define child maltreatment as any act or series of acts of commission or omission by a parent or...

 (physical
Physical abuse
Physical abuse is abuse involving contact intended to cause feelings of intimidation, injury, or other physical suffering or bodily harm.-Forms of physical abuse:*Striking*Punching*Belting*Pushing, pulling*Slapping*Whipping*Striking with an object...

, emotional
Psychological abuse
Psychological abuse, also referred to as emotional abuse or mental abuse, is a form of abuse characterized by a person subjecting or exposing another to behavior that may result in psychological trauma, including anxiety, chronic depression, or post-traumatic stress disorder...

, sexual
Sexual abuse
Sexual abuse, also referred to as molestation, is the forcing of undesired sexual behavior by one person upon another. When that force is immediate, of short duration, or infrequent, it is called sexual assault. The offender is referred to as a sexual abuser or molester...

, or neglect) is also associated with increased risk of developing depressive disorders later in life. Such a link has good face validity given that it is during the years of development that a child is learning how to become a social being. Abuse of the child by the caregiver is bound to distort the developing personality and create a much greater risk for depression and many other debilitating mental and emotional states. Disturbances in family functioning, such as parental (particularly maternal) depression, severe marital conflict or divorce, death of a parent, or other disturbances in parenting are additional risk factors. In adulthood, stressful life events are strongly associated with the onset of major depressive episodes. In this context, life events connected to social rejection appear to be particularly related to depression. Evidence that a first episode of depression is more likely to be immediately preceded by stressful life events than are recurrent ones is consistent with the hypothesis that people may become increasingly sensitized to life stress over successive recurrences of depression.

The relationship between stressful life events and social support
Social support
Social support can be defined and measured in many ways. It can loosely be defined as feeling that one is cared for by and has assistance available from other people and that one is part of a supportive social network...

 has been a matter of some debate; the lack of social support may increase the likelihood that life stress will lead to depression, or the absence of social support may constitute a form of strain that leads to depression directly. There is evidence that neighborhood social disorder, for example, due to crime or illicit drugs, is a risk factor, and that a high neighborhood socioeconomic status, with better amenities, is a protective factor. Adverse conditions at work, particularly demanding jobs with little scope for decision-making, are associated with depression, although diversity and confounding factors make it difficult to confirm that the relationship is causal.

Evolutionary

From the standpoint of evolutionary theory, major depression is hypothesized, in some instances, to increase an individual's reproductive fitness
Fitness (biology)
Fitness is a central idea in evolutionary theory. It can be defined either with respect to a genotype or to a phenotype in a given environment...

. Evolutionary approaches to depression
Evolutionary approaches to depression
Evolutionary psychology has proposed several different evolutionary explanations for depression.- Background :Major depression is a leading cause of disability worldwide, and in 2000 was the fourth leading contributor to the global burden of disease ; it is also an important risk factor for suicide...

 and evolutionary psychology
Evolutionary psychology
Evolutionary psychology is an approach in the social and natural sciences that examines psychological traits such as memory, perception, and language from a modern evolutionary perspective. It seeks to identify which human psychological traits are evolved adaptations, that is, the functional...

 posit specific mechanisms by which depression may have been genetically incorporated into the human gene pool, accounting for the high heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...

 and prevalence of depression by proposing that certain components of depression are adaptations, such as the behaviors relating to attachment
Attachment theory
Attachment theory describes the dynamics of long-term relationships between humans. Its most important tenet is that an infant needs to develop a relationship with at least one primary caregiver for social and emotional development to occur normally. Attachment theory is an interdisciplinary study...

 and social rank
Social class
Social classes are economic or cultural arrangements of groups in society. Class is an essential object of analysis for sociologists, political scientists, economists, anthropologists and social historians. In the social sciences, social class is often discussed in terms of 'social stratification'...

. Current behaviors can be explained as adaptations to regulate relationships or resources, although the result may be maladaptive in modern environments.

From another viewpoint, a counseling therapist may see depression not as a biochemical illness or disorder but as "a species-wide evolved suite of emotional programmes that are mostly activated by a perception, almost always over-negative, of a major decline in personal usefulness, that can sometimes be linked to guilt, shame or perceived rejection". This suite may have manifested in aging hunters in humans' foraging
Foraging
- Definitions and significance of foraging behavior :Foraging is the act of searching for and exploiting food resources. It affects an animal's fitness because it plays an important role in an animal's ability to survive and reproduce...

 past, who were marginalized by their declining skills, and may continue to appear in alienated members
Social alienation
The term social alienation has many discipline-specific uses; Roberts notes how even within the social sciences, it “is used to refer both to a personal psychological state and to a type of social relationship”...

 of today's society. The feelings of uselessness generated by such marginalization could hypothetically prompt support from friends and kin. Additionally, in a manner analogous to that in which physical pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 has evolved to hinder actions that may cause further injury, "psychic misery
Suffering
Suffering, or pain in a broad sense, is an individual's basic affective experience of unpleasantness and aversion associated with harm or threat of harm. Suffering may be qualified as physical or mental. It may come in all degrees of intensity, from mild to intolerable. Factors of duration and...

" may have evolved to prevent hasty and maladaptive reactions to distressing situations.

Drug and alcohol use

According to the DSM-IV, a diagnosis of mood disorder cannot be made if the cause is believed to be due to "the direct physiological effects of a substance"; when a syndrome resembling major depression is believed to be caused immediately by substance abuse or by an adverse drug reaction, it is referred to as, "substance-induced mood disturbance". Alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

 or excessive alcohol consumption significantly increases the risk of developing major depression. Like alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...

s are central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 depressant
Depressant
A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...

s; this class of medication is commonly used to treat insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, and muscular spasms. Similar to alcohol, benzodiazepines increase the risk of developing major depression. This increased risk may be due in part to the effects of drugs on neurochemistry
Neurochemistry
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...

, such as decreased levels of serotonin and norepinephrine. Chronic use of benzodiazepines also can cause or worsen depression, or depression may be part of a protracted withdrawal syndrome.

Clinical assessment

A diagnostic assessment may be conducted by a suitably trained general practitioner
General practitioner
A general practitioner is a medical practitioner who treats acute and chronic illnesses and provides preventive care and health education for all ages and both sexes. They have particular skills in treating people with multiple health issues and comorbidities...

, or by a psychiatrist
Psychiatrist
A psychiatrist is a physician who specializes in the diagnosis and treatment of mental disorders. All psychiatrists are trained in diagnostic evaluation and in psychotherapy...

 or psychologist
Psychologist
Psychologist is a professional or academic title used by individuals who are either:* Clinical professionals who work with patients in a variety of therapeutic contexts .* Scientists conducting psychological research or teaching psychology in a college...

, who records
Psychiatric history
A psychiatric history is the result of a medical process where a clinician working in the field of mental health systematically records the content of an interview with a patient...

 the person's current circumstances, biographical history, current symptoms and family history. The broad clinical aim is to formulate the relevant biological, psychological and social factors that may be impacting on the individual's mood. The assessor may also discuss the person's current ways of regulating their mood (healthy or otherwise) such as alcohol and drug use. The assessment also includes a mental state examination, which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or pessimism, self-harm
Self-harm
Self-harm or deliberate self-harm includes self-injury and self-poisoning and is defined as the intentional, direct injuring of body tissue most often done without suicidal intentions. These terms are used in the more recent literature in an attempt to reach a more neutral terminology...

 or suicide, and an absence of positive thoughts or plans. Specialist mental health services are rare in rural areas, and thus diagnosis and management is largely left to primary care
Primary care
Primary care is the term for the health services by providers who act as the principal point of consultation for patients within a health care system...

 clinicians. This issue is even more marked in developing countries. The score on a rating scale
Rating scale
A rating scale is a set of categories designed to elicit information about a quantitative or a qualitative attribute. In the social sciences, common examples are the Likert scale and 1-10 rating scales in which a person selects the number which is considered to reflect the perceived quality of a...

 alone is insufficient to diagnose depression to the satisfaction of the DSM or ICD, but it provides an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose. Screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

 programs have been advocated to improve detection of depression, but there is evidence that they do not improve detection rates, treatment, or outcome.

Primary care physician
Primary care physician
A primary care physician, or PCP, is a physician/medical doctor who provides both the first contact for a person with an undiagnosed health concern as well as continuing care of varied medical conditions, not limited by cause, organ system, or diagnosis....

s and other non-psychiatrist physicians have difficulty diagnosing depression, in part because they are trained to recognize and treat physical symptoms, and depression can cause a myriad of physical (psychosomatic) symptoms. Non-psychiatrists miss two-thirds of cases and unnecessarily treat other patients.

Before diagnosing a major depressive disorder, a doctor generally performs a medical examination and selected investigations to rule out other causes of symptoms. These include blood tests measuring TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 and thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...

 to exclude hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

; basic electrolytes and serum calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 to rule out a metabolic disturbance; and a full blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...

 including ESR
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...

 to rule out a systemic infection or chronic disease. Adverse affective reactions to medications or alcohol misuse are often ruled out, as well. Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 levels may be evaluated to diagnose hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...

, a cause of depression in men.

Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a dementing disorder
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

, such as Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

. Cognitive testing
Neuropsychological assessment
Neuropsychological assessment was traditionally carried out to assess the extent of impairment to a particular skill and to attempt to locate an area of the brain which may have been damaged after brain injury or neurological illness...

 and brain imaging can help distinguish depression from dementia. A CT scan
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...

 can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. No biological tests confirm major depression. Investigations are not generally repeated for a subsequent episode unless there is a medical indication.

Biomarkers of depression have been sought to provide an objective method of diagnosis. There are several potential biomarkers, including Brain-Derived Neurotrophic Factor and various functional MRI techniques. One study developed a decision tree model of interpreting a series of fMRI scans taken during various activities. In their subjects, the authors of that study were able to achieve a sensitivity of 80% and a sensitivity of 87%, corresponding to a negative predictive value of 98% and a positive predictive value of 32% (positive and negative likelihood ratios were 6.15, 0.23 respectively). However, much more research is needed before these tests could be used clinically.

DSM-IV-TR and ICD-10 criteria

The most widely used criteria for diagnosing depressive conditions are found in the American Psychiatric Association
American Psychiatric Association
The American Psychiatric Association is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the most influential worldwide. Its some 38,000 members are mainly American but some are international...

's revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders
Diagnostic and Statistical Manual of Mental Disorders
The Diagnostic and Statistical Manual of Mental Disorders is published by the American Psychiatric Association and provides a common language and standard criteria for the classification of mental disorders...

(DSM-IV-TR), and the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

's International Statistical Classification of Diseases and Related Health Problems
ICD
The International Statistical Classification of Diseases and Related Health Problems is a medical classification that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease...

(ICD-10) which uses the name recurrent depressive disorder. The latter system is typically used in European countries, while the former is used in the US and many other non-European nations, and the authors of both have worked towards conforming one with the other.

Both DSM-IV-TR and ICD-10 mark out typical (main) depressive symptoms. ICD-10 defines three typical depressive symptoms (depressed mood, anhedonia, and reduced energy), two of which should be present to determine depressive disorder diagnosis. According DSM-IV-TR there are two main depressive symptoms—depressed mood, anhedonia, at least one of which must be present to determine diagnosis of major depressive episode.

Major depressive disorder is classified as a mood disorder in DSM-IV-TR. The diagnosis hinges on the presence of single or recurrent major depressive episode
Major depressive episode
A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday...

s. Further qualifiers are used to classify both the episode itself and the course of the disorder. The category Depressive Disorder Not Otherwise Specified is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode. The ICD-10
ICD-10
The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the...

 system does not use the term major depressive disorder, but lists very similar criteria for the diagnosis of a depressive episode (mild, moderate or severe); the term recurrent may be added if there have been multiple episodes without mania.

Major depressive episode

A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as psychotic depression
Psychotic depression
Psychotic major depression is a type of depression that can include symptoms and treatments that are different from those of non-psychotic major depressive disorder . PMD is estimated to affect about 0.4% of the population .PMD is sometimes "mistaken" for NPMD, schizoaffective disorder,...

—is automatically rated as severe. If the patient has had an episode of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

 or markedly elevated mood
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

, a diagnosis of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

 is made instead. Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole".

DSM-IV-TR excludes cases where the symptoms are a result of bereavement, although it is possible for normal bereavement to evolve into a depressive episode if the mood persists and the characteristic features of a major depressive episode develop. The criteria have been criticized because they do not take into account any other aspects of the personal and social context in which depression can occur. In addition, some studies have found little empirical support for the DSM-IV cut-off criteria, indicating they are a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration: Excluded are a range of related diagnoses, including dysthymia, which involves a chronic but milder mood disturbance; recurrent brief depression
Recurrent brief depression
Recurrent brief depression defines a mental disorder characterized by intermittent depressive episodes, in women not related to menstrual cycles, occurring at least once a month over at least one year or more fulfilling the diagnostic criteria for major depressive episodes except for duration...

, consisting of briefer depressive episodes; minor depressive disorder
Minor depressive disorder
Minor depressive Disorder, also known as Minor Depression, is a mood disorder that does not meet full criteria for Major depressive disorder but in which at least two depressive symptoms are present for two weeks. It is given in the DSM-IV-TR as an example of a Depressive Disorder Not Otherwise...

, whereby only some of the symptoms of major depression are present; and adjustment disorder with depressed mood
Adjustment disorder
Adjustment disorder is a psychological response to an identifiable stressor or group of stressors that cause significant emotional or behavioral symptoms that do not meet criteria for anxiety disorder, PTSD, or acute stress disorder...

, which denotes low mood resulting from a psychological response to an identifiable event or stressor.

Subtypes

The DSM-IV-TR recognizes five further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features:
  • Melancholic depression
    Melancholic depression
    Melancholic depression, or 'depression with melancholic features' is a subtype of major depression characterized by major depressive disorder with the following specific features: anhedonia , severe weight loss, psychomotor agitation or retardation, insomnia with early morning awakenings, guilt...

    is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief
    Grief
    Grief is a multi-faceted response to loss, particularly to the loss of someone or something to which a bond was formed. Although conventionally focused on the emotional response to loss, it also has physical, cognitive, behavioral, social, and philosophical dimensions...

     or loss, a worsening of symptoms in the morning hours, early morning waking, psychomotor retardation
    Psychomotor retardation
    Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...

    , excessive weight loss (not to be confused with anorexia nervosa
    Anorexia nervosa
    Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...

    ), or excessive guilt.
  • Atypical depression
    Atypical depression
    Atypical depression is a subtype of dysthymia and major depression, sharing many of the symptoms of both, but also being characterized by mood reactivity—being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot...

    is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain
    Weight gain
    Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...

     or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia
    Hypersomnia
    Hypersomnia is a disorder characterized by excessive amounts of sleepiness.There are two main categories of hypersomnia: primary hypersomnia and recurrent hypersomnia...

    ), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection
    Social rejection
    Social rejection occurs when an individual is deliberately excluded from a social relationship or social interaction. The topic includes both interpersonal rejection and romantic rejection. A person can be rejected on an individual basis or by an entire group of people...

    .
  • Catatonic
    Catatonia
    Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....

     depression
    is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia
    Schizophrenia
    Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

     or in manic episodes, or may be caused by neuroleptic malignant syndrome
    Neuroleptic malignant syndrome
    Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...

    .
  • Postpartum depression
    Postpartum depression
    Postpartum depression , also called postnatal depression, is a form of clinical depression which can affect women, and less frequently men, typically after childbirth. Studies report prevalence rates among women from 5% to 25%, but methodological differences among the studies make the actual...

    , or mental and behavioural disorders associated with the puerperium, not elsewhere classified, refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression has an incidence rate of 10–15% among new mothers. The DSM-IV mandates that, in order to qualify as postpartum depression, onset occur within one month of delivery. It has been said that postpartum depression can last as long as three months.
  • Seasonal affective disorder
    Seasonal affective disorder
    Seasonal affective disorder , also known as winter depression, winter blues, summer depression, summer blues, or seasonal depression, is a mood disorder in which people who have normal mental health throughout most of the year experience depressive symptoms in the winter or summer, spring or autumn...

    (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.

Differential diagnoses

To confer major depressive disorder as the most likely diagnosis, other potential diagnoses
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 must be considered, including dysthymia, adjustment disorder with depressed mood or bipolar disorder. Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as double depression). Adjustment disorder with depressed mood
Adjustment disorder
Adjustment disorder is a psychological response to an identifiable stressor or group of stressors that cause significant emotional or behavioral symptoms that do not meet criteria for anxiety disorder, PTSD, or acute stress disorder...

 is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode. Bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

, also known as manic–depressive disorder, is a condition in which depressive phases alternate with periods of mania or hypomania
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

. Although depression is currently categorized as a separate disorder, there is ongoing debate because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a mood disorder continuum.

Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, medications, and substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...

. Depression due to physical illness is diagnosed as a mood disorder
Mood disorder
Mood disorder is the term designating a group of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders classification system where a disturbance in the person's mood is hypothesized to be the main underlying feature...

 due to a general medical condition. This condition is determined based on history, laboratory findings, or physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...

. When the depression is caused by a substance abused including a drug of abuse, a medication, or exposure to a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

, it is then diagnosed as a substance-induced mood disorder. In such cases, a substance is judged to be etiologically related to the mood disturbance.

Schizoaffective disorder
Schizoaffective disorder
Schizoaffective disorder is a psychiatric diagnosis that describes a mental disorder characterized by recurring episodes of elevated or depressed mood, or of simultaneously elevated and depressed mood, that alternate with, or occur together with, distortions in perception.Schizoaffective disorder...

 is different from major depressive disorder with psychotic features because in the schizoaffective disorder at least two weeks of delusions or hallucinations must occur in the absence of prominent mood symptoms.

Depressive symptoms may be identified during schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, delusional disorder
Delusional disorder
Delusional disorder is an uncommon psychiatric condition in which patients present with circumscribed symptoms of non-bizarre delusions, but with the absence of prominent hallucinations and no thought disorder, mood disorder, or significant flattening of affect...

, and psychotic disorder not otherwise specified, and in such cases those symptoms are considered associated features of these disorders, therefore, a separate diagnosis is not deemed necessary unless the depressive symptoms meet full criteria for a major depressive episode. In that case, a diagnosis of depressive disorder not otherwise specified may be made as well as a diagnosis of schizophrenia.

Some cognitive symptoms of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

 such as disorientation, apathy
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...

, difficulty concentrating and memory loss
Memory loss
Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...

 may get confused with a major depressive episode in major depressive disorder. They are especially difficult to determine in elderly patients. In such cases, the premorbid state of the patient may be helpful to differentiate both disorders. In the case of dementia, there tends to be a premorbid history of declining cognitive function. In the case of a major depressive disorder patients tend to exhibit a relatively normal premorbid state and abrupt cognitive decline associated with the depression.

Prevention

Behavioral interventions, such as interpersonal therapy, are effective at preventing new onset depression. Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet
Internet
The Internet is a global system of interconnected computer networks that use the standard Internet protocol suite to serve billions of users worldwide...

. However, an earlier meta-analysis found preventive programs with a competence-enhancing component to be superior to behaviorally oriented programs overall, and found behavioral programs to be particularly unhelpful for older people, for whom social support programs were uniquely beneficial. Additionally, the programs that best prevented depression comprised more than eight sessions, each lasting between 60 and 90 minutes, were provided by a combination of lay and professional workers, had a high-quality research design, reported attrition rates
Churn rate
Churn rate , in its broadest sense, is a measure of the number of individuals or items moving into or out of a collective over a specific period of time...

, and had a well-defined intervention. The "Coping with Depression" course (CWD) is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.

Management

The three most common treatments for depression are psychotherapy, medication, and electroconvulsive therapy.
Psychotherapy is the treatment of choice for people under 18, while electroconvulsive therapy is only used as a last resort. Care is usually given on an outpatient basis, while treatment in an inpatient unit is considered if there is a significant risk to self or others.

Treatment options are much more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition. Physical exercise
Physical exercise
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...

 is recommended for management of mild depression, but it has only a moderate, statistically insignificant effect on symptoms in most cases of major depressive disorder.

Psychotherapy


Psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

 can be delivered, to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical social work
Social work
Social Work is a professional and academic discipline that seeks to improve the quality of life and wellbeing of an individual, group, or community by intervening through research, policy, community organizing, direct practice, and teaching on behalf of those afflicted with poverty or any real or...

ers, counselors, and suitably trained psychiatric nurses. With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used.

Cognitive behavioral therapy (CBT) currently has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression. In people under 18, according to the National Institute for Health and Clinical Excellence
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...

, medication should only be offered in conjunction with a psychological therapy, such as CBT, interpersonal therapy
Interpersonal psychotherapy
Interpersonal Psychotherapy is a time-limited psychotherapy that focuses on the interpersonal context and on building interpersonal skills. IPT is based on the belief that interpersonal factors may contribute heavily to psychological problems. It is commonly distinguished from other forms of...

, or family therapy.

Psychotherapy has been shown to be effective in older people. Successful psychotherapy appears to reduce the recurrence of depression even after it has been terminated or replaced by occasional booster sessions.

The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring ways of thinking (cognitions) and change counter-productive behaviors. Research beginning in the mid-1990s suggested that CBT could perform as well or better than antidepressants in patients with moderate to severe depression. CBT may be effective in depressed adolescents, although its effects on severe episodes are not definitively known. Combining fluoxetine with CBT appeared to bring no additional benefit, or, at the most, only marginal benefit. Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer cognitive distortions. CBT is particularly beneficial in preventing relapse.
Several variants of cognitive behavior therapy have been used in depressed patients, most notably rational emotive behavior therapy
Rational emotive behavior therapy
Rational emotive behavior therapy , previously called rational therapy and rational emotive therapy, is a comprehensive, active-directive, philosophically and empirically based psychotherapy which focuses on resolving emotional and behavioral problems and disturbances and enabling people to lead...

, and more recently mindfulness-based cognitive therapy
Mindfulness-based Cognitive Therapy
Mindfulness-based cognitive therapy is psychological therapy which blends features of cognitive therapy with mindfulness techniques of Buddhism. MBCT involves accepting thoughts and feelings without judgement rather than trying to push them out of consciousness, with a goal of correcting...

.

Psychoanalysis
Psychoanalysis
Psychoanalysis is a psychological theory developed in the late 19th and early 20th centuries by Austrian neurologist Sigmund Freud. Psychoanalysis has expanded, been criticized and developed in different directions, mostly by some of Freud's former students, such as Alfred Adler and Carl Gustav...

 is a school of thought, founded by Sigmund Freud
Sigmund Freud
Sigmund Freud , born Sigismund Schlomo Freud , was an Austrian neurologist who founded the discipline of psychoanalysis...

, which emphasizes the resolution of unconscious
Unconscious mind
The unconscious mind is a term coined by the 18th century German romantic philosopher Friedrich Schelling and later introduced into English by the poet and essayist Samuel Taylor Coleridge...

 mental conflicts. Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression. A more widely practiced, eclectic
Eclecticism
Eclecticism is a conceptual approach that does not hold rigidly to a single paradigm or set of assumptions, but instead draws upon multiple theories, styles, or ideas to gain complementary insights into a subject, or applies different theories in particular cases.It can sometimes seem inelegant or...

 technique, called psychodynamic psychotherapy
Psychodynamic psychotherapy
Psychodynamic psychotherapy is a form of depth psychology, the primary focus of which is to reveal the unconscious content of a client's psyche in an effort to alleviate psychic tension. In this way, it is similar to psychoanalysis. It also relies on the interpersonal relationship between client...

, is loosely based on psychoanalysis and has an additional social and interpersonal focus. In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression.

Logotherapy
Logotherapy
Logotherapy was developed by neurologist and psychiatrist Viktor Frankl. It is considered the "Third Viennese School of Psychotherapy" after Freud's psychoanalysis and Adler's individual psychology. It is a type of existentialist analysis that focuses on a will to meaning as opposed to Adler's...

, a form of existential psychotherapy developed by Austrian psychiatrist Viktor Frankl
Viktor Frankl
Viktor Emil Frankl M.D., Ph.D. was an Austrian neurologist and psychiatrist as well as a Holocaust survivor. Frankl was the founder of logotherapy, which is a form of Existential Analysis, the "Third Viennese School of Psychotherapy"...

, addresses the filling of an "existential vacuum" associated with feelings of futility and meaninglessness. It is posited that this type of psychotherapy may be useful for depression in older adolescents.

Koreans use two different coping methods: emotion-focused coping and problem-focused coping. Emotion-focused coping decreases emotional distress through avoidance, distancing, and finding positive values in negative events. Problem-focused coping influences environmental conditions by altering the source of stress or changing one's self (example. finding alternative ways of gratification).

Antidepressants

The effectiveness of antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

s is none to minimal in those with mild or moderate depression but significant in those with very severe disease. The effects of antidepressants are somewhat superior to those of psychotherapy, especially in cases of chronic major depression, although in short-term trials more patients—especially those with less serious forms of depression—cease medication than cease psychotherapy, most likely due to adverse effects
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

 from the medication and to patients' preferences for psychological therapies over pharmacological treatments.

To find the most effective antidepressant medication with minimal side effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50–75%, and it can take at least six to eight weeks from the start of medication to remission
Cure
A cure is a completely effective treatment for a disease.The Cure is an English rock band.Cure, or similar, may also refer to:-Film and television:* The Cure , a short film starring Charlie Chaplin...

, when the patient is back to their normal self. Antidepressant medication treatment is usually continued for 16 to 20 weeks after remission, to minimize the chance of recurrence, and even up to one year of continuation is recommended. People with chronic depression may need to take medication indefinitely to avoid relapse.

Selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

s (SSRIs) are the primary medications prescribed owing to their effectiveness, relatively mild side effects, and because they are less toxic in overdose than other antidepressants. Patients who do not respond to one SSRI can be switched to another antidepressant, and this results in improvement in almost 50% of cases. Another option is to switch to the atypical antidepressant bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...

. Venlafaxine
Venlafaxine
Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...

, an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs. However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits, and it is specifically discouraged in children and adolescents.
For adolescent depression, fluoxetine and escitalopram are the two recommended choices. Antidepressants have not been found to be beneficial in children. There is also insufficient evidence to determine effectiveness in those with depression complicated by dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

. Any antidepressant can cause low serum sodium levels (also called hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...

); nevertheless, it has been reported more often with SSRIs. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating antidepressant mirtazapine
Mirtazapine
Mirtazapine is a tetracyclic antidepressant used primarily in the treatment of depression. It is also sometimes used as a hypnotic, antiemetic, and appetite stimulant, and for the treatment of anxiety, among other indications...

 can be used in such cases.

Irreversible monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

s, an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better tolerated agents of this class have been developed. The safety profile is different with reversible monoamine oxidase inhibitor's such as moclobemide
Moclobemide
Moclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...

 where the risk of serious dietary interactions is negligible and dietry restrictions are less 'strict'.

The terms "refractory depression" and "treatment-resistant depression" are used to describe cases that do not respond to adequate courses of at least two antidepressants. In many major studies, only about 35% of patients respond well to medical treatment. It may be difficult for a doctor to decide when someone has treatment-resistant depression or whether the problem is due to coexisting disorders, which are common among patients with major depression.

A team of psychologists from multiple American universities found that antidepressant drugs hardly have better effects than a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

 in cases of mild or moderate depression. The study focused on paroxetine and imipramine.


For children, adolescents, and probably young adults between 18–24 years old, there is a higher risk of both suicidal ideations and suicidal behavior in those treated with SSRIs. For adults, it is unclear whether or not SSRIs affect the risk of suicidality. One review found no connection; another an increased risk; and a third no risk in those 25–65 years old and a decrease risk in those more than 65. Epidemiological data has found that the widespread use of antidepressants in the new “SSRI-era” is associated with a significant decline in suicide rates in most countries with traditionally high baseline suicide rates. The causality of the relationship is inconclusive. A black box warning
Black box warning
In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects...

 was introduced in the United States in 2007 on SSRI and other antidepressant medications due to increased risk of suicide in patients younger than 24 years old. Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.

Fish oil supplements containing high levels of eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...

 to docosahexaenoic acid
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain and retina. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end...

 have been established as effective in major depression. There is some preliminary evidence that COX-2 inhibitors have a beneficial effect on major depression.

Electroconvulsive therapy

Electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...

 (ECT) is a procedure whereby pulses of electricity are sent through the brain via two electrodes, usually one on each temple
Temple (anatomy)
Temple indicates the side of the head behind the eyes. The bone beneath is the temporal bone as well as part of the sphenoid bone.-Anatomy:Cladists classify land vertebrates based on the presence of an upper hole, a lower hole, both, or neither in the cover of dermal bone which formerly covered the...

, to induce a seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

 while the patient is under a brief period of general anesthesia
General anaesthetic
A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthesia provider to induce or maintain general anaesthesia to facilitate surgery...

. Hospital psychiatrists may recommend ECT for cases of severe major depression which have not responded to antidepressant medication or, less often, psychotherapy or supportive interventions. ECT can have a quicker effect than antidepressant therapy and thus may be the treatment of choice in emergencies such as catatonic depression where the patient has stopped eating and drinking, or where a patient is severely suicidal. ECT is probably more effective than pharmacotherapy for depression in the immediate short-term, although a landmark community-based study found much lower remission rates in routine practice. When ECT is used on its own, the relapse rate within the first six months is very high; early studies put the rate at around 50%, while a more recent controlled trial found rates of 84% even with placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

s. The early relapse rate may be reduced by the use of psychiatric medications or further ECT (although the latter is not recommended by some authorities) but remains high. Common initial adverse effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

 from ECT include short
Short-term memory
Short-term memory is the capacity for holding a small amount of information in mind in an active, readily available state for a short period of time. The duration of short-term memory is believed to be in the order of seconds. A commonly cited capacity is 7 ± 2 elements...

 and long-term memory
Long-term memory
Long-term memory is memory in which associations among items are stored, as part of the theory of a dual-store memory model. According to the theory, long term memory differs structurally and functionally from working memory or short-term memory, which ostensibly stores items for only around 20–30...

 loss, disorientation and headache. Although memory disturbance after ECT
Anterograde amnesia
Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...

 usually resolves within one month, ECT remains a controversial treatment, and debate on its efficacy and safety continues.

Prognosis

Major depressive episodes often resolve over time whether or not they are treated. Outpatients on a waiting list show a 10–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder. The median
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...

 duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months.

Studies have shown that 80% of those suffering from their first major depressive episode will suffer from at least 1 more during their life, with a lifetime average of 4 episodes. Other general population studies indicate around half those who have an episode (whether treated or not) recover and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence. Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence.

Recurrence is more likely if symptoms have not fully resolved with treatment. Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

s indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use.

Those people who experience repeated episodes of depression require ongoing treatment in order to prevent more severe, long-term depression
Long-term depression
Long-term depression , in neurophysiology, is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress...

. In some cases, people need to take medications for long periods of time or for the rest of their lives.

Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms that may include psychosis, early age of onset, more previous episodes, incomplete recovery after 1 year, pre-existing severe mental or medical disorder, and family dysfunction as well.

Depressed individuals have a shorter life expectancy
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...

 than those without depression, in part because depressed patients are at risk of dying by suicide. However, they also have a higher rate of dying
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

 from other causes, being more susceptible to medical conditions such as heart disease. Up to 60% of people who commit suicide have a mood disorder such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and borderline personality disorder
Borderline personality disorder
Borderline personality disorder is a personality disorder described as a prolonged disturbance of personality function in a person , characterized by depth and variability of moods.The disorder typically involves unusual levels of instability in mood; black and white thinking, or splitting; the...

. The lifetime risk of suicide associated with a diagnosis of major depression in the US is estimated at 3.4%, which averages two highly disparate figures of almost 7% for men and 1% for women (although suicide attempts are more frequent in women). The estimate is substantially lower than a previously accepted figure of 15% which had been derived from older studies of hospitalized patients.

Depression is often associated with unemployment and poverty. Major depression is currently the leading cause of disease burden
Disease burden
Disease burden is the impact of a health problem in an area measured by financial cost, mortality, morbidity, or other indicators. It is often quantified in terms of quality-adjusted life years or disability-adjusted life years , which combine the burden due to both death and morbidity into one...

 in North America and other high-income countries, and the fourth-leading cause worldwide. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

, according to the World Health Organization. Delay or failure in seeking treatment after relapse, and the failure of health professionals to provide treatment, are two barriers to reducing disability.

Prevalence

Depression is a major cause of morbidity worldwide. Lifetime prevalence varies widely, from 3% in Japan to 17% in the US. In most countries the number of people who would suffer from depression during their lives falls within an 8–12% range. In North America the probability of having a major depressive episode within a year-long period is 3–5% for males and 8–10% for females. Population studies have consistently shown major depression to be about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this. The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors.

People are most likely to suffer their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60. The risk of major depression is increased with neurological conditions such as stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, or multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

 and during the first year after childbirth. It is also more common after cardiovascular illnesses, and is related more to a poor outcome than to a better one. Studies conflict on the prevalence of depression in the elderly, but most data suggest there is a reduction in this age group. Depressive disorders are most common to observe in urban than in rural population and the prevalence is in groups with stronger socioeconomic factors i.e. homelessness

By country

Comorbidity

Major depression frequently co-occurs
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...

 with other psychiatric problems. The 1990–92 National Comorbidity Survey (US) reports that 51% of those with major depression also suffer from lifetime anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

. Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicide attempts. American neuroendocrinologist Robert Sapolsky
Robert Sapolsky
Robert Maurice Sapolsky is an American scientist and author. He is currently Professor of Biological Sciences, and Professor of Neurology and Neurological Sciences and, by courtesy, Neurosurgery, at Stanford University. In addition, he is a Research Associate at the National Museums of...

 similarly argues that the relationship between stress, anxiety, and depression could be measured and demonstrated biologically. There are increased rates of alcohol and drug abuse and particularly dependence, and around a third of individuals diagnosed with ADHD
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

 develop comorbid depression. Post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 and depression often co-occur.

Depression and pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

 often co-occur, especially if it is chronic or uncontrollable pain . This conforms with Seligman's theory of learned helplessness
Learned helplessness
Learned helplessness, as a technical term in animal psychology and related human psychology, means a condition of a human person or an animal in which it has learned to behave helplessly, even when the opportunity is restored for it to help itself by avoiding an unpleasant or harmful circumstance...

. One or more pain symptoms is present in 65% of depressed patients, and anywhere from five to 85% of patients with pain will be suffering from depression, depending on the setting; there is a lower prevalence in general practice, and higher in specialty clinics. The diagnosis of depression is often delayed or missed, and the outcome worsens. The outcome can also obviously worsen if the depression is noticed but completely misunderstood

Depression is also associated with a 1.5- to 2-fold increased risk of cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

, independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating cardiovascular disorders, which further increases their risk. In addition, cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.

History

The Ancient Greek physician Hippocrates
Hippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...

 described a syndrome of melancholia as a distinct disease with particular mental and physical symptoms; he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment. It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included.

The term depression itself was derived from the Latin verb deprimere, "to press down". From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author Richard Baker's
Richard Baker (chronicler)
Sir Richard Baker was the English author of the Chronicle of the Kings of England and other works.-Life:He was probably born at Sissinghurst in Kent, the grandson of Sir John Baker, the first Chancellor of the Exchequer. He entered Hart Hall, Oxford, as a commoner in 1584...

 Chronicle to refer to someone having "a great depression of spirit", and by English author Samuel Johnson
Samuel Johnson
Samuel Johnson , often referred to as Dr. Johnson, was an English author who made lasting contributions to English literature as a poet, essayist, moralist, literary critic, biographer, editor and lexicographer...

 in a similar sense in 1753. The term also came in to use in physiology
Depression (physiology)
Depression in physiology and medicine refers to a lowering, in particular a reduction in a particular biological variable or the function of an organ...

 and economics
Depression (economics)
In economics, a depression is a sustained, long-term downturn in economic activity in one or more economies. It is a more severe downturn than a recession, which is seen by some economists as part of the modern business cycle....

. An early usage referring to a psychiatric symptom was by French psychiatrist Louis Delasiauve
Louis Delasiauve
Louis Jean Francois Delasiauve was a French psychiatrist who was a native of Garennes-sur-Eure. In 1830 he earned his doctorate in Paris, and for the next eight years practiced medicine in Ivry. Afterwards he worked at the Bicêtre Hospital, and later became a director at the Salpêtrière, where he...

 in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function. Since Aristotle
Aristotle
Aristotle was a Greek philosopher and polymath, a student of Plato and teacher of Alexander the Great. His writings cover many subjects, including physics, metaphysics, poetry, theater, music, logic, rhetoric, linguistics, politics, government, ethics, biology, and zoology...

, melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. The newer concept abandoned these associations and through the 19th century, became more associated with women.

Although melancholia remained the dominant diagnostic term, depression gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist Emil Kraepelin
Emil Kraepelin
Emil Kraepelin was a German psychiatrist. H.J. Eysenck's Encyclopedia of Psychology identifies him as the founder of modern scientific psychiatry, as well as of psychopharmacology and psychiatric genetics. Kraepelin believed the chief origin of psychiatric disease to be biological and genetic...

 may have been the first to use it as the overarching term, referring to different kinds of melancholia as depressive states.

Sigmund Freud likened the state of melancholia to mourning in his 1917 paper Mourning and Melancholia. He theorized that objective
Object (philosophy)
An object in philosophy is a technical term often used in contrast to the term subject. Consciousness is a state of cognition that includes the subject, which can never be doubted as only it can be the one who doubts, and some object or objects that may or may not have real existence without...

 loss, such as the loss of a valued relationship through death or a romantic break-up, results in subjective
Subject (philosophy)
In philosophy, a subject is a being that has subjective experiences, subjective consciousness or a relationship with another entity . A subject is an observer and an object is a thing observed...

 loss as well; the depressed individual has identified with the object of affection through an unconscious
Unconscious mind
The unconscious mind is a term coined by the 18th century German romantic philosopher Friedrich Schelling and later introduced into English by the poet and essayist Samuel Taylor Coleridge...

, narcissistic
Narcissism
Narcissism is a term with a wide range of meanings, depending on whether it is used to describe a central concept of psychoanalytic theory, a mental illness, a social or cultural problem, or simply a personality trait...

 process called the libidinal cathexis
Cathexis
In psychoanalysis, cathexis is defined as the process of investment of mental or emotional energy in a person, object, or idea. The Greek term cathexis was chosen by James Strachey to render the German term Besetzung in his translation of Sigmund Freud's complete works. For Freud, cathexis is...

of the ego. Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively, but the ego itself is compromised. The patient's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness. He also emphasized early life experiences as a predisposing factor. Meyer put forward a mixed social and biological framework emphasizing reactions in the context of an individual's life, and argued that the term depression should be used instead of melancholia. The first version of the DSM (DSM-I, 1952) contained depressive reaction and the DSM-II (1968) depressive neurosis, defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders.

In the mid-20th century, researchers theorized that depression was caused by a chemical imbalance in neurotransmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...

 and isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...

 in altering monoamine neurotransmitter levels and affecting depressive symptoms.

The term Major depressive disorder was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the "Research Diagnostic Criteria", building on earlier Feighner Criteria), and was incorporated in to the DSM-III in 1980. To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a mild depressive episode, adding higher threshold categories for moderate and severe episodes. The ancient idea of melancholia still survives in the notion of a melancholic subtype.

The new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia. There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s.

Society and culture

People's conceptualizations of depression vary widely, both within and among cultures. "Because of the lack of scientific certainty," one commentator has observed, "the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it." There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or is an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle.

The diagnosis is less common in some countries, such as China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...

. It has been argued that the Chinese traditionally deny or somatize
Somatization
Somatization is currently defined as "a tendency to experience and communicate somatic distress in response to psychosocial stress and to seek medical help for it".This can be, but not always, related to a psychological condition:...

 emotional depression (although since the early 1980's, the Chinese denial of depression may have modified drastically). Alternatively, it may be that Western cultures reframe and elevate some expressions of human distress to disorder status. Australian professor Gordon Parker
Gordon Parker
Gordon Parker is Scientia Professor of Psychiatry at the University of New South Wales, specializing in clinical research in mental health in particular depression & bipolar disorder....

 and others have argued that the Western concept of depression "medicalizes" sadness or misery. Similarly, Hungarian-American psychiatrist Thomas Szasz
Thomas Szasz
Thomas Stephen Szasz is a psychiatrist and academic. Since 1990 he has been Professor Emeritus of Psychiatry at the State University of New York Health Science Center in Syracuse, New York. He is a well-known social critic of the moral and scientific foundations of psychiatry, and of the social...

 and others argue that depression is a metaphorical illness that is inappropriately regarded as an actual disease. There has also been concern that the DSM, as well as the field of descriptive psychiatry
Descriptive psychiatry
Descriptive psychiatry is based on the study of observable symptoms and behavioral phenomena rather than underlying psychodynamic processes. In descriptive psychiatry, the clinical psychiatrist focuses on empirically observable behaviors and conditions, such as words spoken or actions taken.Modern...

 that employs it, tends to reify
Reification (fallacy)
Reification is a fallacy of ambiguity, when an abstraction is treated as if it were a concrete, real event, or physical entity. In other words, it is the error of treating as a "real thing" something which is not a real thing, but merely an idea...

 abstract phenomena such as depression, which may in fact be social constructs
Social constructionism
Social constructionism and social constructivism are sociological theories of knowledge that consider how social phenomena or objects of consciousness develop in social contexts. A social construction is a concept or practice that is the construct of a particular group...

. American archetypal psychologist
Archetypal psychology
Archetypal psychology is a vein of inquiry into the psyche inaugurated in the early 1900s by Carl Gustav Jung. Jung and his followers, as well as Mircea Eliade, imagined the psychology of the archetypes from studying anthropology and archeology reports of their times and weaving it into their...

 James Hillman
James Hillman
James Hillman was an American psychologist. He studied at, and then guided studies for, the C.G. Jung Institute in Zurich, founded a movement toward archetypal psychology and retired into private practice, writing and traveling to lecture, until his death at his home in Connecticut on October 27,...

 writes that depression can be healthy for the soul, insofar as "it brings refuge, limitation, focus, gravity, weight, and humble powerlessness." Hillman argues that therapeutic attempts to eliminate depression echo the Christian theme of resurrection
Resurrection
Resurrection refers to the literal coming back to life of the biologically dead. It is used both with respect to particular individuals or the belief in a General Resurrection of the dead at the end of the world. The General Resurrection is featured prominently in Jewish, Christian, and Muslim...

, but have the unfortunate effect of demonizing a soulful state of being.


Historical figures were often reluctant to discuss or seek treatment for depression due to social stigma
Social stigma
Social stigma is the severe disapproval of or discontent with a person on the grounds of characteristics that distinguish them from other members of a society.Almost all stigma is based on a person differing from social or cultural norms...

 about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author Mary Shelley
Mary Shelley
Mary Shelley was a British novelist, short story writer, dramatist, essayist, biographer, and travel writer, best known for her Gothic novel Frankenstein: or, The Modern Prometheus . She also edited and promoted the works of her husband, the Romantic poet and philosopher Percy Bysshe Shelley...

, American-British writer Henry James
Henry James
Henry James, OM was an American-born writer, regarded as one of the key figures of 19th-century literary realism. He was the son of Henry James, Sr., a clergyman, and the brother of philosopher and psychologist William James and diarist Alice James....

, and American president Abraham Lincoln
Abraham Lincoln
Abraham Lincoln was the 16th President of the United States, serving from March 1861 until his assassination in April 1865. He successfully led his country through a great constitutional, military and moral crisis – the American Civil War – preserving the Union, while ending slavery, and...

. Some well-known contemporary people with possible depression include Canadian songwriter Leonard Cohen
Leonard Cohen
Leonard Norman Cohen, is a Canadian singer-songwriter, musician, poet and novelist. Cohen published his first book of poetry in Montreal in 1956 and his first novel in 1963. His work often explores religion, isolation, sexuality and interpersonal relationships...

  and American playwright and novelist Tennessee Williams
Tennessee Williams
Thomas Lanier "Tennessee" Williams III was an American writer who worked principally as a playwright in the American theater. He also wrote short stories, novels, poetry, essays, screenplays and a volume of memoirs...

. Some pioneering psychologists, such as Americans William James
William James
William James was a pioneering American psychologist and philosopher who was trained as a physician. He wrote influential books on the young science of psychology, educational psychology, psychology of religious experience and mysticism, and on the philosophy of pragmatism...

  and John B. Watson
John B. Watson
John Broadus Watson was an American psychologist who established the psychological school of behaviorism. Watson promoted a change in psychology through his address Psychology as the Behaviorist Views it which was given at Columbia University in 1913...

, dealt with their own depression.

There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity
Creativity
Creativity refers to the phenomenon whereby a person creates something new that has some kind of value. What counts as "new" may be in reference to the individual creator, or to the society or domain within which the novelty occurs...

, a discussion that goes back to Aristotelian times. British literature gives many examples of reflections on depression. English philosopher John Stuart Mill
John Stuart Mill
John Stuart Mill was a British philosopher, economist and civil servant. An influential contributor to social theory, political theory, and political economy, his conception of liberty justified the freedom of the individual in opposition to unlimited state control. He was a proponent of...

 experienced a several-months-long period of what he called "a dull state of nerves", when one is "unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent". He quoted English poet Samuel Taylor Coleridge
Samuel Taylor Coleridge
Samuel Taylor Coleridge was an English poet, Romantic, literary critic and philosopher who, with his friend William Wordsworth, was a founder of the Romantic Movement in England and a member of the Lake Poets. He is probably best known for his poems The Rime of the Ancient Mariner and Kubla...

's "Dejection" as a perfect description of his case: "A grief without a pang, void, dark and drear, / A drowsy, stifled, unimpassioned grief, / Which finds no natural outlet or relief / In word, or sigh, or tear." English writer Samuel Johnson
Samuel Johnson
Samuel Johnson , often referred to as Dr. Johnson, was an English author who made lasting contributions to English literature as a poet, essayist, moralist, literary critic, biographer, editor and lexicographer...

 used the term "the black dog" in the 1780s to describe his own depression, and it was subsequently popularized by depression sufferer former British Prime Minister Sir Winston Churchill
Winston Churchill
Sir Winston Leonard Spencer-Churchill, was a predominantly Conservative British politician and statesman known for his leadership of the United Kingdom during the Second World War. He is widely regarded as one of the greatest wartime leaders of the century and served as Prime Minister twice...

.

Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on treatment differ markedly to those of health professionals; alternative treatments are held to be more helpful than pharmacological ones, which are viewed poorly. In the UK, the Royal College of Psychiatrists
Royal College of Psychiatrists
The Royal College of Psychiatrists is the main professional organisation of psychiatrists in the United Kingdom responsible for representing psychiatrists, psychiatric research and providing public information about mental health problems...

 and the Royal College of General Practitioners
Royal College of General Practitioners
The Royal College of General Practitioners is the professional body for general practitioners in the United Kingdom. The RCGP represents and supports GPs on key issues including licensing, education, training, research and clinical standards. It is the largest of the medical royal colleges, with...

 conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996; a MORI study conducted afterwards showed a small positive change in public attitudes to depression and treatment.

External links

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