Causes of schizophrenia
Encyclopedia
The causes of schizophrenia have been the subject of much debate, with various factors proposed and discounted or modified. The language of schizophrenia
research under the medical model is scientific. Such studies suggest that genetics
, prenatal development, early environment, neurobiology and psychological and social processes are important contributory factors.
Current psychiatric research into the development of the disorder is often based on a neurodevelopmental model (proponents of which see schizophrenia as a syndrome.) However,
schizophrenia is diagnosed on the basis of symptom profiles
. Neural
correlates do not provide sufficiently useful criteria. "Current research into schizophrenia has remained highly fragmented, much like the clinical presentation of the disease itself".
Although no common cause of schizophrenia has been identified in all individuals diagnosed with the condition, currently most researchers and clinicians believe it results from a combination of both brain
vulnerabilities (either inherited or acquired) and life events. This widely adopted approach is known as the 'stress-vulnerability' model, and much scientific debate now focuses on how much each of these factors contributes to the development and maintenance of schizophrenia.
Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood, suggesting it is often the end process of childhood and adolescent development. There is on average a somewhat earlier onset for men than women, with the possible influence of the female hormone estrogen
being one hypothesis and sociocultural influences another.
.
Both individual twin studies and meta-analyses of twin studies estimate the heritability
of risk for schizophrenia to be approximately 80% (this refers to the proportion of variation between individuals in a population that is influenced by genetic factors, not the degree of genetic determination of individual risk). Concordance rates between monozygotic twins was close to 50%; whereas dizygotic twins was 17%. Adoption studies have also indicated a somewhat increased risk in those with a parent with schizophrenia even when raised apart. Studies suggest that the phenotype
is genetically influenced but not genetically determined; that the variants in genes are generally within the range of normal human variation and have low risk associated with them each individually; and that some interact with each other and with environmental risk factors; and that they may not be specific to schizophrenia.
Some twin studies have found rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins, however.
Tyronne Cannon reviewed the situation, stating: "Previous twin studies have reported estimates of broad heritability ranging from 0.41 to 0.87" Yet, in the "Pairs of Veteran Twins" study, for example, 338 pairs were schizophrenic with only 26 pairs concordant, and it was concluded in one report: "the role of the suggested genetic factor appears to be a limited one; 85 percent of the affected monozygotic pairs in the sample were discordant for schizophrenia". In addition, some scientists criticize the methodology of the twin studies, and have argued that the genetic basis of schizophrenia is still largely unknown or open to different interpretations.
For example, although the concordance of schizophrenia occurrence in monozygotic twins has traditionally been used to estimate a genetic component to the illness, the results could be skewed because of environmental factors like a shared placenta
In fact, researchers, have used the phenomenon of 'fetal programming' to account for familial patterns in epidemiological studies. "Intra-uterine growth is a complex outcome that is influenced by a wide range of factors including fetal genotype, maternal physiology and behaviour as well as the function of that crucial interface—the placenta," said one journal.
After reviewing techniques like: Genome Wide Association Studies; Single Nucleotide Polymorphisms and Copy Number Variations; the Nature journal reports: the basic observation is that, "You have this clear tangible phenomenon in which children resemble their parents"...."Despite what children get told in elementary school science we just don't know how that works," as Professor of ecology and evolutionary biology at Princeton, Leonid Kruglyak, says (in reviewing hereditibility in general). It cites schizophrenia as a trait in which the genes have gone missing.
A great deal of effort has been put into molecular genetic
studies of schizophrenia, which attempt to identify specific genes which may increase risk. A 2003 review of linkage
studies listed seven genes as likely to increase risk for a later diagnosis of the disorder. Two recent reviews suggested that the evidence was strongest for two genes known as dysbindin
(DTNBP1) and neuregulin
(NRG1), and that a number of other genes (such as COMT, RGS4
, PPP3CC
, ZDHHC8
, DISC1
, and AKT1
) showed some early promising results. Variations near the gene FXYD6
have also been associated with schizophrenia in the UK but not in Japan. In 2008, rs7341475
SNP
of the reelin
gene was associated with an increased risk of schizophrenia in women, but not in men. This female-specific association was replicated in several populations. Still another review found evidence that the protein phosphatase 2B (calcineurin) might be involved in susceptibility to schizophrenia.
The largest most comprehensive genetic study of its kind, involving tests of several hundred single nucleotide polymorphisms (SNPs) in nearly 1,900 individuals with schizophrenia or schizoaffective disorder and 2,000 comparison subjects, reported in 2008 that there was no evidence of any significant association between the disorders and any of 14 previously identified candidate gene
s (RGS4
, DISC1
, DTNBP1, STX7
, TAAR6
,
PPP3CC
, NRG1, DRD2, HTR2A, DAOA, AKT1
,
CHRNA7
, COMT, and ARVCF
). The statistical distributions suggested nothing more than chance variation. The authors concluded that the findings make it unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects could not be ruled out.
The perhaps largest analysis of genetic associations in schizophrenia is with the SzGene database at the Schizophrenia Research Forum
.
One 2008 meta-analysis
examined genetic variants in 16 genes and found nominally significant effects.
Other research has suggested that a greater than average number of rare deletions or duplications of tiny DNA sequences within genes (known as copy number variants
) are linked to increased risk for schizophrenia, especially in those "sporadic" cases not linked to family history of schizophrenia, and that the genetic factors and developmental pathways can thus be different in different individuals. A genome wide survey of 3,391 individuals with schizophrenia found CNVs in less than 1% of cases. Within them, deletions in regions related to psychosis
were observed, as well as deletions on chromosome 15q13.3 and 1q21.1
.
CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions). This results in deletions and duplications of dosage sensitive genes. It has been speculated that CNVs underlie a significant proportion of normal human variation, including differences in cognitive, behavioral, and psychological features, and that CNVs in at least three loci can result in increased risk for schizophrenia in a few individuals.
Epigenetics
may also play a role in schizophrenia, with the expression of Protocadherin 11 X/Protocadherin Y playing a possible role in schizophrenia.
A 2009 study was able to create mice matching schizophrenic symptoms by the deletion of only one gene set, those of the neuregulin
post-synaptic receptor. The result showed that although the mice mostly developed normally, on further brain development, glutamate receptors brokedown. This theory supports the glutamate hypothesis of schizophrenia
.
Another study in 2009 by Simon Fraser University researchers identifies a link between Autism and Schizophrenia :
"The SFU group found that variations in four sets of genes
are related to both autism
and schizophrenia
. People normally have two copies of each gene, but in autistics some genome locations have only single copies and in schizophrenics extra copies are present at the same locations." "Source"
increasing genes may increase reproductive success by increasing such traits such as creativity, verbal ability, and emotional sensitivity.
Another evolutionary explanations is the "imprinted brain theory
" which argues that psychosis and autism
are contrasting disorders on a number of different variables. This is argued to be caused by an unbalanced genomic imprinting favoring paternal genes in the case of autism and maternal genes in the case of psychosis.
One epidemiological finding is that people diagnosed with schizophrenia are more likely to have been born in winter
or spring
(at least in the northern hemisphere
). However, the effect is not large. Explanations have included a greater prevalence of viral infections at that time, or a greater likelihood of vitamin D
deficiency. A similar effect (increased likelihood of being born in winter and spring) has also been found with other, healthy populations, such as chess players.
Women who were pregnant during the Dutch famine of 1944
, where many people were close to starvation (experiencing malnutrition
) had a higher chance of having a child who would later develop schizophrenia. Studies of Finnish
mothers who were pregnant when they found out that their husbands had been killed during the Winter War
of 1939–1940 have shown that their children were significantly more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy, suggesting that maternal stress may have an effect.
Animal models have suggested links between intrauterine growth restriction and specific neurological abnormalities similar to those that may be involved in the development of schizophrenia, including ventricular enlargement and reduced hippocampal volume in guinea pigs.
(low oxygen levels) before, at or immediately after birth may be a risk factor for the development of schizophrenia.
Hypoxia is now being demonstrated as relevant to schizophrenia in animal models, molecular biology and epidemiology studies. One study in Molecular Psychiatry was able to differentiate 90% of schizophrenics from controls based on hypoxia and metabolism. Hypoxia has been recently described as one of the most important of the external factors that influence susceptibility, although studies have been mainly epidemiological. Such studies place a high degree of importance on hypoxic influence, but because of familial pattern of the illness in some families, propose a genetic factor also; stopping short of concluding hypoxia to be the sole cause. Fetal hypoxia
, in the presence of certain unidentified genes, has been correlated with reduced volume of the hippocampus
, which is in turn correlated with schizophrenia.
Although most studies have interpreted hypoxia as causing some form of neuronal dysfunction or even subtle damage, it has been suggested that the physiological hypoxia that prevails in normal embryonic and fetal development, or pathological hypoxia or ischemia
, may exert an effect by regulating or dysregulating genes involved in neurodevelopment. A literature review judged that over 50% of the candidate gene
s for susceptibility to schizophrenia met criteria for "ischemia–hypoxia regulation and/or vascular
expression" even though only 3.5% of all genes were estimated to be involved in hypoxia/ischemia or the vasculature.
A longitudinal study found that obstetric complications involving hypoxia were one factor associated with neurodevelopmental impairments in childhood and with the later development of schizophreniform disorders. Fetal hypoxia has been found to predict unusual movements at age 4 (but not age 7) among children who go on to develop schizophrenia, suggesting that its effects are specific to the stage of neurodevelopment. A Japanese case study of monozygotic twins discordant for schizophrenia (one has the diagnosis while the other does not) draws attention to their different weights at birth and concludes hypoxia may be the differentiating factor.
The unusual functional laterality in speech production (e.g. right hemisphere auditory processing) found in some individuals with schizophrenia could be due to aberrant neural networks established as a compensation for left temporal lobe damage induced by pre- or perinatal hypoxia. Prenatal and perinatal hypoxia appears to be important as one factor in the neurodevelopmental model, with the important implication that some forms of schizophrenia may thus be preventable.
Research on rodents seeking to understand the possible role of prenatal hypoxia in disorders such as schizophrenia has indicated that it can lead to a range of sensorimotor and learning/memory abnormalities. Impairments in motor function and coordination, evident on challenging tasks when the hypoxia was severe enough to cause brain damage, were long-lasting and described as a "hallmark of prenatal hypoxia".
Several animal studies have indicated that fetal hypoxia can affect many of the same neural substrates implicated in schizophrenia, depending on the severity and duration of the hypoxic event as well as the period of gestation, and in humans moderate or severe (but not mild) fetal hypoxia has been linked to a series of motor, language and cognitive deficits in children, regardless of genetic liability to schizophrenia. One paper restated that cerebellum
neurological disorders were frequently found in schizophrenics and speculated hypoxia may cause the subsequent cognitive dysmetria
Whereas most studies find only a modest effect of hypoxia in schizophrenia, a longitudinal study using a combination of indicators to detect possible fetal hypoxia, such as early equivalents of Neurological Soft Signs or obstetric complications, reported that the risk of schizophrenia and other nonaffective psychoses was "strikingly elevated" (5.75% versus 0.39%). Although objective estimates of hypoxia did not account for all schizophrenic cases; the study revealed increasing odds of schizophrenia according to graded increase in severity of hypoxia.
has been linked to schizophrenia, possibly due to "chromosomal aberrations and mutations of the aging germline." Maternal-fetal rhesus or genotype incompatibility has also been linked, via increasing the risk of an adverse prenatal environment. Also, in mothers with schizophrenia, an increased risk has been identified via a complex interaction between maternal genotype, maternal behavior, prenatal environment and possibly medication and socioeconomic factors. References for many of these environmental risk factors have been collected in an online database.
There may be an association between celiac disease (gluten
intolerance) and schizophrenia in a small proportion of patients, though large randomized controlled trials and epidemiological
studies will be needed before such an association can be confirmed. Withdrawal of gluten from the diet is an inexpensive measure which may improve the symptoms in a small (≤3%) number of schizophrenic patients.
In addition, there is some evidence that exposure to toxins such as lead
can also increase the risk of later development of schizophrenia spectrum disorders.
Influenza
has long been studied as a possible factor. A 1988 study found that individuals who were exposed to the Asian flu as second trimester fetuses were at increased risk of eventually developing schizophrenia. This result was corroborated by a later British study of the same pandemic, but not by a 1994 study of the pandemic in Croatia. A Japanese study also found no support for a link between schizophrenia and birth after an influenza epidemic.
Polio, measles
, varicella-zoster, rubella
, herpes simplex
virus type 2, maternal genital infections, Borna disease virus
, and more recently Toxoplasma gondii
, have been correlated with the later development of schizophrenia. Psychiatrists E. Fuller Torrey
and R.H. Yolken have hypothesized that the latter, a common parasite in humans, contributes to some, if not many, cases of schizophrenia.
In a meta-analysis of several studies, they found moderately higher levels of Toxoplasma antibodies in those with schizophrenia and possibly higher rates of prenatal or early postnatal exposure to Toxoplasma gondii, but not acute infection. However, in another study of postmortem brain tissue, the authors have reported equivocal or negative results, including no evidence of herpes virus or T. gondii involvement in schizophrenia.
There is some evidence for the role of autoimmunity
in the development of some cases of schizophrenia. A statistical correlation has been reported with various autoimmune diseases and direct studies have linked dysfunctional immune status to some of the clinical features of schizophrenia.
This is known as the pathogenic theory of schizophrenia or germ theory of schizophrenia. It is a pathogenic theory of disease in which it is thought that a proximal cause of certain cases of schizophrenia
is the interaction of the developing fetus with pathogen
s such as virus
es, or with antibodies from the mother created in response to these pathogens (in particular, Interleukin 8
). Substantial research suggests that exposure to certain illnesses (e.g., influenza) in the mother of the neonate (especially at the end of the second trimester) causes defects in neural development which may emerge as a predisposition to schizophrenia around the time of puberty, as the brain grows and develops.
A prospective study found average differences across a range of developmental domains, including reaching milestones of motor development at a later age, having more speech problems, lower educational test results, solitary play preferences at ages four and six, and being more socially anxious at age 13. Lower ratings of the mother's skills and understanding of the child at age 4 were also related.
Some of the early developmental differences were identified in the first year of life in a study in Finland, although generally related to psychotic disorders rather than schizophrenia in particular. The early subtle motor signs persisted to some extent, showing a small link to later school performance in adolescence. An earlier Finnish study found that childhood performance of 400 individuals diagnosed with schizophrenia was significantly worse than controls on subjects involving motor co-ordination (sports and handcrafts) between ages 7 and 9, but there were no differences on academic subjects (contrary to some other IQ findings). (Patients in this age group with these symptoms were significantly less likely to progress to high school, despite academic ability)
However, reanalysis of the data from the later Finnish study, on older children (14 to 16) in a changed school system, using narrower diagnostic criteria and with less cases but more controls, did not support a significant difference on sports and handicraft performance. However, another study found that unusual motor coordination scores at 7 years of age were associated in adulthood with both those with schizophrenia and their unaffected siblings, while unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status.
A birth cohort study in New Zealand found that children who went on to develop schizophreniform disorder
had, as well as emotional problems and interpersonal difficulties linked to all adult psychiatric outcomes measured, significant impairments in neuromotor, receptive language, and cognitive development. A retrospective study found that adults with schizophrenia had performed better than average in artistic subjects at ages 12 and 15, and in linguistic and religious subjects at age 12, but worse than average in gymnastics at age 15.
Some small studies on offspring of individuals with schizophrenia have identified various neurobehavioral deficits, a poorer family environment and disruptive school behaviour, poor peer engagement, immaturity or unpopularity or poorer social competence and increasing schizophrenic symptomology emerging during adolescence.
A minority "deficit syndrome" subtype of schizophrenia is proposed to be more marked by early poor adjustment and behavioral problems, as compared to non-deficit subtypes.
and anhedonia
are all considered to be core features.
The rate of substance use is known to be particularly high in this group. In a recent study, 60% of people with schizophrenia were found to use substances and 37% would be diagnosable with a substance use disorder.
use can contribute to schizophrenia. Some studies suggest that cannabis is neither a sufficient nor necessary factor in developing schizophrenia, but that cannabis may significantly
increase the risk of developing schizophrenia and may be, among other things, a significant causal factor. Nevertheless, some previous research in this area has been criticised as it has often not been clear whether cannabis use is a cause or effect of schizophrenia. To address this issue, a recent review of studies from which a causal contribution to schizophrenia can be assessed has suggested that cannabis statistically doubles the risk of developing schizophrenia on the individual level, and may, assuming a causal relationship, be responsible for up to 8% of cases in the population.
An older longitudinal study
, published in 1987, suggested a sixfold increase of schizophrenia risks for high consumers of cannabis (use on more than fifty occasions) in Sweden
.
Despite increases in cannabis consumption in the 1960s and 1970s in western society, rates of psychotic disorders such as schizophrenia remained relatively stable over time.
Also, Sweden and Japan, where self-reported marijuana use is very low, do not have lower rates of psychosis than the U.S. and Canada do. Thus, there remains controversy over whether or not the apparent association between cannabis and schizophrenia is a causal relationship.
), amphetamines may worsen schizophrenia symptoms. In addition, amphetamines are known to cause a stimulant psychosis in otherwise healthy individuals that superficially resembles schizophrenia, and may be misdiagnosed as such by some healthcare professionals.
, PCP
, and LSD
have been used to mimic schizophrenia for research purposes. Using LSD and other psychedelics as a model has now fallen out of favor with the scientific research community, as the differences between the drug induced states and the typical presentation of schizophrenia have become clear. The dissociatives ketamine and PCP, however, are still considered to produce states that are remarkably similar however, and are considered to be even better models than stimulants since they produce both positive and negative symptoms.
, Scotland
found a 58% prevalence rate of cigarette smoking, to compare with 28% in the general population. An older study found that as much as 88% of outpatients with schizophrenia were smokers.
Despite the higher prevalence of tobacco smoking, people diagnosed with schizophrenia have a much lower than average chance of developing and dying from lung cancer
. While the reason for this is unknown, it may be because of a genetic resistance to the cancer, a side effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer.
A 2003 study of over 50,000 Swedish
conscripts found that there was a small but significant
protective effect of smoking cigarettes on the risk of developing schizophrenia later in life. While the authors of the study stressed that the risks of smoking far outweigh these minor benefits, this study provides further evidence for the 'self-medication
' theory of smoking in schizophrenia and may give clues as to how schizophrenia might develop at the molecular level. Furthermore, many people with schizophrenia have smoked tobacco products long before they are diagnosed with the illness, and a cohort study of Israeli conscripts found that healthy adolescent smokers were more likely to develop schizophrenia in the future than their nonsmoking peers.
It is of interest that cigarette smoking affects liver function such that the antipsychotic drugs used to treat schizophrenia are broken down in the blood stream more quickly. This means that smokers with schizophrenia need slightly higher doses of antipsychotic drugs in order for them to be effective than do their non-smoking counterparts.
The increased rate of smoking in schizophrenia may be due to a desire to self-medicate with nicotine
. One possible reason is that smoking produces a short term effect to improve alertness and cognitive functioning in persons who suffer this illness. It has been postulated that the mechanism of this effect is that people with schizophrenia have a disturbance of nicotinic receptor functioning which is temporarily abated by tobacco use. However, some researchers have questioned whether self-medication is really the best explanation for the association.
A study from 1989 and a 2004 case study show that when haloperidol is administered, nicotine limits the extent to which the antipsychotic increases the sensitivity
of the dopamine 2 receptor. Dependent on the dopamine system, symptoms of Tardive Dyskinesia
are not found in the nicotine administered patients despite a roughly 70% increase in dopamine receptor activity, but the controls have more than 90% and do develop symptoms.A 1997 study showed that akathisia
was significantly reduced upon administration of nicotine when the akathisia was induced by antipsychotics. This gives credence to the idea tobacco could be used to self medicate by limiting effects of the illness, the medication, or both.
) present in childhood. Stressful life events generally precede the onset of schizophrenia. A personal or recent family history of migration is a considerable risk factor for schizophrenia, which has been linked to psychosocial adversity, social defeat from being an outsider, racial discrimination, family dysfunction, unemployment
and poor housing conditions. Unemployment and early separation from parents are some important factors which are responsible for the higher rates of schizophrenia among British African Caribbean, in comparison to native African Caribbean. This is an example which shows that social disadvantage plays an equally major hand in onset schizophrenia as genetics.
Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life. Recent large-scale general population studies indicate the relationship is a causal one, with an increasing risk with additional experiences of maltreatment, although a critical review suggests conceptual and methodological issues require further research. There is some evidence that adversities may lead to cognitive biases and/or altered dopamine neurotransmission, a process that has been termed "sensitization".
Specific social experiences have been linked to specific psychological mechanisms and psychotic experiences in schizophrenia. In addition, structural neuroimaging studies of victims of sexual abuse and other traumas have sometimes reported findings similar to those sometimes found in psychotic patients, such as thinning of the corpus callosum, loss of volume in the anterior cingulate cortex, and reduced hippocampal volume.
environment and the development of schizophrenia, even after factors such as drug use
, ethnic group
and size of social group have been controlled for. A recent study of 4.4 million men and women in Sweden
found a 68%–77% increased risk of diagnosed psychosis
for people living in the most urbanized environments, a significant proportion of which is likely to be described as schizophrenia.
The effect does not appear to be due to a higher incidence of obstetric complications in urban environments. The risk increases with the number of years and degree of urban living in childhood and adolescence, suggesting that constant, cumulative, or repeated exposures during upbringing occurring more frequently in urbanized areas are responsible for the association.
Various possible explanations for the effect have been judged unlikely based on the nature of the findings, including infectious causes or a generic
stress effect. It is thought to interact with genetic dispositions and, since there appears to be nonrandom variation even across different neighborhoods, and an independent association with social isolation, it has been proposed that the degree of "social capital" (e.g. degree of mutual trust, bonding and safety in neighborhoods) can exert a developmental impact on children growing up in these environments.
, Theodore Lidz
and others have argued that the symptoms of what is called mental illness are comprehensible reactions to impossible demands that society and particularly family life places on some sensitive individuals. Laing, Arieti and Lidz were notable in valuing the content of psychotic
experience as worthy of interpretation, rather than considering it simply as a secondary and essentially meaningless marker of underlying psychological or neurological distress. Laing described eleven case studies of people diagnosed with schizophrenia and argued that the content of their actions and statements was meaningful and logical in the context of their family and life situations.
In 1956, Gregory Bateson
and his colleagues Paul Watzlawick
, Donald Jackson
, and Jay Haley
articulated a theory of schizophrenia, related to Laing's work, as stemming from double bind
situations where a person receives different or contradictory messages. Madness was therefore an expression of this distress and should be valued as a cathartic
and transformative experience. In the books Schizophrenia and the Family and The Origin and Treatment of Schizophrenic Disorders Lidz and his colleagues explain their belief that parental behaviour can result in mental illness in children. Arieti's Interpretation of Schizophrenia won the 1975 scientific National Book Award
in the United States.
The concept of schizophrenia as a result of civilization has been developed further by psychologist Julian Jaynes
in his 1976 book The Origin of Consciousness in the Breakdown of the Bicameral Mind; he proposed that until the beginning of historic times, schizophrenia or a similar condition was the normal state of human consciousness. This would take the form of a "bicameral mind" where a normal state of low affect, suitable for routine activities, would be interrupted in moments of crisis by "mysterious voices" giving instructions, which early people characterized as interventions from the gods. Researchers into shamanism have speculated that in some cultures schizophrenia or related conditions may predispose an individual to becoming a shaman; the experience of having access to multiple realities is not uncommon in schizophrenia, and is a core experience in many shamanic traditions. Equally, the shaman may have the skill to bring on and direct some of the altered states of consciousness
psychiatrists label as illness. Psychohistorians
, on the other hand, accept the psychiatric diagnoses. However, unlike the current medical model of mental disorders
they may argue that poor parenting in tribal societies causes the shaman's schizoid personalities. Commentators such as Paul Kurtz
and others have endorsed the idea that major religious figures experienced psychosis, heard voices and displayed delusions of grandeur.
Modern clinical psychological research has indicated a number of processes which may cause or bring on episodes of schizophrenia.
A number of cognitive bias
es and deficits have been identified. These include attribution biases in social situations, difficulty distinguishing inner speech from speech from an external source (source monitoring), difficulty in adjusting speech to the needs of the hearer, difficulties in the very earliest stages of processing visual information (including reduced latent inhibition
), and an attentional bias
towards threats.
Some of these tendencies have been shown to worsen or appear when under emotional stress or in confusing situations. As with related neurological findings, they are not shown by all individuals with a diagnosis of schizophrenia, and it is not clear how specific they are to schizophrenia. However, the findings regarding cognitive difficulties in schizophrenia are reliable and consistent enough for some researchers to argue that they are diagnostic.
Impaired capacity to appreciate one's own and others' mental states has been reported to be the single-best predictor of poor social competence in schizophrenia, and similar cognitive features have been identified in close relatives of people diagnosed with schizophrenia.
A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, but more recent studies indicate there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations. Some theories suggest positive symptoms of schizophrenia can result from or be worsened by negative emotions, including depressed feelings and low self-esteem
and feelings of vulnerability, inferiority or loneliness
. Chronic negative feelings and maladaptive coping skills may explain some of the association between psychosocial stressors and symptomology. Critical and controlling behaviour by significant others (high expressed emotion
) causes increased emotional arousal and lowered self-esteem and a subsequent increase in positive symptoms such as unusual thoughts. Countries or cultures where schizotypal personalities or schizophrenia symptoms are more accepted or valued appear to be associated with reduced onset of, or increased recovery from, schizophrenia.
Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history, or social circumstances of the individual. Holding minority socio-cultural beliefs, for example due to ethnic background, has been linked to increased diagnosis of schizophrenia. The way an individual interprets his or her delusions and hallucinations (e.g. as threatening or as potentially positive) has also been found to influence functioning and recovery.
Some experts think autonomy vs intimacy is a motivation for schizophrenic symptoms.
Other lines of work relating to the self in schizophrenia have linked it to psychological dissociation
or abnormal states of awareness and identity as understood from phenomenological and other perspectives.
Psychiatrist Tim Crow
has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language
. Since psychosis is associated with greater levels of right brain hemisphere activation and a reduction in the usual left brain hemisphere dominance, our language abilities may have evolved at the cost of causing schizophrenia when this system breaks down.
In alternative medicine
, some practitioners believe that there are a vast number of physical causes of what ends up being diagnosed as schizophrenia. While some of these explanations may stretch credulity, others (such as heavy metal poisoning and nutritional imbalances) have been supported at least somewhat by research. However, it is not entirely clear how many patients initially diagnosed with schizophrenia these alternative explanations may account for.
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...
research under the medical model is scientific. Such studies suggest that genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, prenatal development, early environment, neurobiology and psychological and social processes are important contributory factors.
Current psychiatric research into the development of the disorder is often based on a neurodevelopmental model (proponents of which see schizophrenia as a syndrome.) However,
schizophrenia is diagnosed on the basis of symptom profiles
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...
. Neural
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
correlates do not provide sufficiently useful criteria. "Current research into schizophrenia has remained highly fragmented, much like the clinical presentation of the disease itself".
Although no common cause of schizophrenia has been identified in all individuals diagnosed with the condition, currently most researchers and clinicians believe it results from a combination of both 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...
vulnerabilities (either inherited or acquired) and life events. This widely adopted approach is known as the 'stress-vulnerability' model, and much scientific debate now focuses on how much each of these factors contributes to the development and maintenance of schizophrenia.
Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood, suggesting it is often the end process of childhood and adolescent development. There is on average a somewhat earlier onset for men than women, with the possible influence of the female 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...
being one hypothesis and sociocultural influences another.
Genetics
Evidence suggests that genetic vulnerability and environmental factors can act in combination to result in diagnosis of schizophrenia. Research suggests that genetic vulnerability to schizophrenia is multifactorial, caused by interactions of several genesGênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
.
Both individual twin studies and meta-analyses of twin studies estimate 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 risk for schizophrenia to be approximately 80% (this refers to the proportion of variation between individuals in a population that is influenced by genetic factors, not the degree of genetic determination of individual risk). Concordance rates between monozygotic twins was close to 50%; whereas dizygotic twins was 17%. Adoption studies have also indicated a somewhat increased risk in those with a parent with schizophrenia even when raised apart. Studies suggest that the phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
is genetically influenced but not genetically determined; that the variants in genes are generally within the range of normal human variation and have low risk associated with them each individually; and that some interact with each other and with environmental risk factors; and that they may not be specific to schizophrenia.
Some twin studies have found rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins, however.
Tyronne Cannon reviewed the situation, stating: "Previous twin studies have reported estimates of broad heritability ranging from 0.41 to 0.87" Yet, in the "Pairs of Veteran Twins" study, for example, 338 pairs were schizophrenic with only 26 pairs concordant, and it was concluded in one report: "the role of the suggested genetic factor appears to be a limited one; 85 percent of the affected monozygotic pairs in the sample were discordant for schizophrenia". In addition, some scientists criticize the methodology of the twin studies, and have argued that the genetic basis of schizophrenia is still largely unknown or open to different interpretations.
For example, although the concordance of schizophrenia occurrence in monozygotic twins has traditionally been used to estimate a genetic component to the illness, the results could be skewed because of environmental factors like a shared placenta
In fact, researchers, have used the phenomenon of 'fetal programming' to account for familial patterns in epidemiological studies. "Intra-uterine growth is a complex outcome that is influenced by a wide range of factors including fetal genotype, maternal physiology and behaviour as well as the function of that crucial interface—the placenta," said one journal.
After reviewing techniques like: Genome Wide Association Studies; Single Nucleotide Polymorphisms and Copy Number Variations; the Nature journal reports: the basic observation is that, "You have this clear tangible phenomenon in which children resemble their parents"...."Despite what children get told in elementary school science we just don't know how that works," as Professor of ecology and evolutionary biology at Princeton, Leonid Kruglyak, says (in reviewing hereditibility in general). It cites schizophrenia as a trait in which the genes have gone missing.
A great deal of effort has been put into molecular genetic
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
studies of schizophrenia, which attempt to identify specific genes which may increase risk. A 2003 review of linkage
Genetic linkage
Genetic linkage is the tendency of certain loci or alleles to be inherited together. Genetic loci that are physically close to one another on the same chromosome tend to stay together during meiosis, and are thus genetically linked.-Background:...
studies listed seven genes as likely to increase risk for a later diagnosis of the disorder. Two recent reviews suggested that the evidence was strongest for two genes known as dysbindin
Dysbindin
Dysbindin, short for dystrobrevin-binding protein 1, is a protein constituent of the dystrophin-associated protein complex of skeletal muscle cells. It is also a part of BLOC-1, or biogenesis of lysosome-related organelles complex 1. Dysbindin was discovered by the research group of Derek Blake...
(DTNBP1) and neuregulin
Neuregulin
The Neuregulins are a family of four structurally-related proteins that are part of the EGF family of proteins. These proteins have been shown to have diverse functions in the development of the nervous system and play multiple essential roles in vertebrate embryogenesis including: cardiac...
(NRG1), and that a number of other genes (such as COMT, RGS4
RGS4
Regulator of G protein signaling 4 or RGS4 is a protein which regulates G protein signaling. A number of studies associate the RGS4 gene with schizophrenia, while some fail to detect an association....
, PPP3CC
PPP3CC
Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PPP3CC gene.-Further reading:...
, ZDHHC8
ZDHHC8
ZDHHC8 is a putative palmitoyltransferase enzyme containing a DHHC domain that in humans is encoded by the ZDHHC8 gene.-Further reading:...
, DISC1
DISC1
Disrupted in schizophrenia 1 is a protein that is encoded by the DISC1 gene in humans. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth,...
, and AKT1
AKT1
RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
) showed some early promising results. Variations near the gene FXYD6
FXYD6
FXYD6 , or FXYD domain-containing ion transport regulator 6, is a gene which is located at the 11q23.3 . The FXYD6 protein contains 95 amino acids, and can be found in all human tissues except blood....
have also been associated with schizophrenia in the UK but not in Japan. In 2008, rs7341475
Rs7341475
In genetics, rs7341475 is a single nucleotide polymorphism in the RELN gene that codes the reelin protein.The gene is located in the fourth intron on human chromosome 7....
SNP
Single nucleotide polymorphism
A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
of the reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
gene was associated with an increased risk of schizophrenia in women, but not in men. This female-specific association was replicated in several populations. Still another review found evidence that the protein phosphatase 2B (calcineurin) might be involved in susceptibility to schizophrenia.
The largest most comprehensive genetic study of its kind, involving tests of several hundred single nucleotide polymorphisms (SNPs) in nearly 1,900 individuals with schizophrenia or schizoaffective disorder and 2,000 comparison subjects, reported in 2008 that there was no evidence of any significant association between the disorders and any of 14 previously identified candidate gene
Candidate gene
A candidate gene is a gene, located in a chromosome region suspected of being involved in the expression of a trait such as a disease, whose protein product suggests that it could be the gene in question...
s (RGS4
RGS4
Regulator of G protein signaling 4 or RGS4 is a protein which regulates G protein signaling. A number of studies associate the RGS4 gene with schizophrenia, while some fail to detect an association....
, DISC1
DISC1
Disrupted in schizophrenia 1 is a protein that is encoded by the DISC1 gene in humans. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth,...
, DTNBP1, STX7
STX7
Syntaxin-7 is a protein that in humans is encoded by the STX7 gene.In melanocytic cells STX7 gene expression may be regulated by MITF.-Interactions:STX7 has been shown to interact with STX8, VPS18, Vesicle-associated membrane protein 8 and VPS11....
, TAAR6
TAAR6
Trace amine associated receptor 6, also known as TAAR6, is a protein which in humans is encoded by the TAAR6 gene.- Function :TAAR6 belongs to the trace amine-associated receptor family. Trace amines are endogenous amine compounds that are chemically similar to classic biogenic amines like...
,
PPP3CC
PPP3CC
Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PPP3CC gene.-Further reading:...
, NRG1, DRD2, HTR2A, DAOA, AKT1
AKT1
RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
,
CHRNA7
CHRNA7
Neuronal acetylcholine receptor subunit alpha-7 is a protein that in humans is encoded by the CHRNA7 gene.-See also:* Alpha-7 nicotinic receptor* Nicotinic acetylcholine receptor* Acetylcholine receptor...
, COMT, and ARVCF
ARVCF
Armadillo repeat protein deleted in velo-cardio-facial syndrome is a protein that in humans is encoded by the ARVCF gene.-Further reading:...
). The statistical distributions suggested nothing more than chance variation. The authors concluded that the findings make it unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects could not be ruled out.
The perhaps largest analysis of genetic associations in schizophrenia is with the SzGene database at the Schizophrenia Research Forum
Schizophrenia Research Forum
Schizophrenia Research Forum is a website dedicated to convey information about schizophrenia.It hosts the SzGene Database, which provides a comprehensive, unbiased and regularly updated field synopsis of genetic association studies performed in schizophrenia with hundreds of up-to-date...
.
One 2008 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...
examined genetic variants in 16 genes and found nominally significant effects.
Other research has suggested that a greater than average number of rare deletions or duplications of tiny DNA sequences within genes (known as copy number variants
Gene copy number
Copy-number variations —a form of structural variation—are alterations of the DNA of a genome that results in the cell having an abnormal number of copies of one or more sections of the DNA. CNVs correspond to relatively large regions of the genome that have been deleted or duplicated on certain...
) are linked to increased risk for schizophrenia, especially in those "sporadic" cases not linked to family history of schizophrenia, and that the genetic factors and developmental pathways can thus be different in different individuals. A genome wide survey of 3,391 individuals with schizophrenia found CNVs in less than 1% of cases. Within them, deletions in regions related to 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"...
were observed, as well as deletions on chromosome 15q13.3 and 1q21.1
1q21.1 deletion syndrome
1q21.1 deletion syndrome or 1q21.1 microdeletion is a rare aberration of chromosome 1. , the international rare chromosome disorder group, has 48 genetically confirmed registered cases of this deletion worldwide ....
.
CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions). This results in deletions and duplications of dosage sensitive genes. It has been speculated that CNVs underlie a significant proportion of normal human variation, including differences in cognitive, behavioral, and psychological features, and that CNVs in at least three loci can result in increased risk for schizophrenia in a few individuals.
Epigenetics
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
may also play a role in schizophrenia, with the expression of Protocadherin 11 X/Protocadherin Y playing a possible role in schizophrenia.
A 2009 study was able to create mice matching schizophrenic symptoms by the deletion of only one gene set, those of the neuregulin
Neuregulin
The Neuregulins are a family of four structurally-related proteins that are part of the EGF family of proteins. These proteins have been shown to have diverse functions in the development of the nervous system and play multiple essential roles in vertebrate embryogenesis including: cardiac...
post-synaptic receptor. The result showed that although the mice mostly developed normally, on further brain development, glutamate receptors brokedown. This theory supports the glutamate hypothesis of schizophrenia
Glutamate hypothesis of schizophrenia
The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors...
.
Another study in 2009 by Simon Fraser University researchers identifies a link between Autism and Schizophrenia :
"The SFU group found that variations in four sets of genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
are related to both autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and 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...
. People normally have two copies of each gene, but in autistics some genome locations have only single copies and in schizophrenics extra copies are present at the same locations." "Source"
Evolutionary psychology
Schizophrenia has been considered an evolutionary puzzle due to the combination of high heritability, relatively high prevalence, and reduced reproductive success. One explanation could be increased reproductive success by close relatives without symptoms but this does not seem to be the case. Still, it has been argued that it is possible that a low amount of schizotypySchizotypy
Schizotypy is a psychological concept which describes a continuum of personality characteristics and experiences ranging from normal dissociative, imaginative states to more extreme states related to psychosis and in particular, schizophrenia...
increasing genes may increase reproductive success by increasing such traits such as creativity, verbal ability, and emotional sensitivity.
Another evolutionary explanations is the "imprinted brain theory
Imprinted brain theory
The imprinted brain theory is an evolutionary psychology theory regarding the causes of autism spectrum disorders and psychosis.- The conflict theory of imprinting :...
" which argues that psychosis and autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
are contrasting disorders on a number of different variables. This is argued to be caused by an unbalanced genomic imprinting favoring paternal genes in the case of autism and maternal genes in the case of psychosis.
Prenatal
It is well established that obstetric complications or events are associated with an increased chance of the child later developing schizophrenia, although overall they constitute a non-specific risk factor with a relatively small effect. Obstetric complications occur in approximately 25 to 30% of the general population and the vast majority do not develop schizophrenia, and likewise the majority of individuals with schizophrenia have not had a detectable obstetric event. Nevertheless, the increased average risk is well-replicated, and such events may moderate the effects of genetic or other environmental risk factors. The specific complications or events most linked to schizophrenia, and the mechanisms of their effects, are still under examination.One epidemiological finding is that people diagnosed with schizophrenia are more likely to have been born in winter
Winter
Winter is the coldest season of the year in temperate climates, between autumn and spring. At the winter solstice, the days are shortest and the nights are longest, with days lengthening as the season progresses after the solstice.-Meteorology:...
or spring
Spring (season)
Spring is one of the four temperate seasons, the transition period between winter and summer. Spring and "springtime" refer to the season, and broadly to ideas of rebirth, renewal and regrowth. The specific definition of the exact timing of "spring" varies according to local climate, cultures and...
(at least in the northern hemisphere
Northern Hemisphere
The Northern Hemisphere is the half of a planet that is north of its equator—the word hemisphere literally means “half sphere”. It is also that half of the celestial sphere north of the celestial equator...
). However, the effect is not large. Explanations have included a greater prevalence of viral infections at that time, or a greater likelihood of vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
deficiency. A similar effect (increased likelihood of being born in winter and spring) has also been found with other, healthy populations, such as chess players.
Women who were pregnant during the Dutch famine of 1944
Dutch famine of 1944
The Dutch famine of 1944, known as the Hongerwinter in Dutch, was a famine that took place in the German-occupied part of the Netherlands, especially in the densely populated western provinces above the great rivers, during the winter of 1944-1945, near the end of World War II. A German blockade...
, where many people were close to starvation (experiencing malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
) had a higher chance of having a child who would later develop schizophrenia. Studies of Finnish
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
mothers who were pregnant when they found out that their husbands had been killed during the Winter War
Winter War
The Winter War was a military conflict between the Soviet Union and Finland. It began with a Soviet offensive on 30 November 1939 – three months after the start of World War II and the Soviet invasion of Poland – and ended on 13 March 1940 with the Moscow Peace Treaty...
of 1939–1940 have shown that their children were significantly more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy, suggesting that maternal stress may have an effect.
Fetal growth
Lower than average birth weight has been one of the most consistent findings, indicating slowed fetal growth possibly mediated by genetic effects. Almost any factor adversely affecting the fetus will affect growth rate, however, so the association has been described as not particularly informative regarding causation. In addition, the majority of birth cohort studies have failed to find a link between schizophrenia and low birth weight or other signs of growth retardation.Animal models have suggested links between intrauterine growth restriction and specific neurological abnormalities similar to those that may be involved in the development of schizophrenia, including ventricular enlargement and reduced hippocampal volume in guinea pigs.
Hypoxia
It has been hypothesized since the 1970s that brain hypoxiaHypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
(low oxygen levels) before, at or immediately after birth may be a risk factor for the development of schizophrenia.
Hypoxia is now being demonstrated as relevant to schizophrenia in animal models, molecular biology and epidemiology studies. One study in Molecular Psychiatry was able to differentiate 90% of schizophrenics from controls based on hypoxia and metabolism. Hypoxia has been recently described as one of the most important of the external factors that influence susceptibility, although studies have been mainly epidemiological. Such studies place a high degree of importance on hypoxic influence, but because of familial pattern of the illness in some families, propose a genetic factor also; stopping short of concluding hypoxia to be the sole cause. Fetal hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
, in the presence of certain unidentified genes, has been correlated with reduced volume of the 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...
, which is in turn correlated with schizophrenia.
Although most studies have interpreted hypoxia as causing some form of neuronal dysfunction or even subtle damage, it has been suggested that the physiological hypoxia that prevails in normal embryonic and fetal development, or pathological hypoxia or ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, may exert an effect by regulating or dysregulating genes involved in neurodevelopment. A literature review judged that over 50% of the candidate gene
Candidate gene
A candidate gene is a gene, located in a chromosome region suspected of being involved in the expression of a trait such as a disease, whose protein product suggests that it could be the gene in question...
s for susceptibility to schizophrenia met criteria for "ischemia–hypoxia regulation and/or vascular
Vascular
Vascular in zoology and medicine means "related to blood vessels", which are part of the circulatory system. An organ or tissue that is vascularized is heavily endowed with blood vessels and thus richly supplied with blood....
expression" even though only 3.5% of all genes were estimated to be involved in hypoxia/ischemia or the vasculature.
A longitudinal study found that obstetric complications involving hypoxia were one factor associated with neurodevelopmental impairments in childhood and with the later development of schizophreniform disorders. Fetal hypoxia has been found to predict unusual movements at age 4 (but not age 7) among children who go on to develop schizophrenia, suggesting that its effects are specific to the stage of neurodevelopment. A Japanese case study of monozygotic twins discordant for schizophrenia (one has the diagnosis while the other does not) draws attention to their different weights at birth and concludes hypoxia may be the differentiating factor.
The unusual functional laterality in speech production (e.g. right hemisphere auditory processing) found in some individuals with schizophrenia could be due to aberrant neural networks established as a compensation for left temporal lobe damage induced by pre- or perinatal hypoxia. Prenatal and perinatal hypoxia appears to be important as one factor in the neurodevelopmental model, with the important implication that some forms of schizophrenia may thus be preventable.
Research on rodents seeking to understand the possible role of prenatal hypoxia in disorders such as schizophrenia has indicated that it can lead to a range of sensorimotor and learning/memory abnormalities. Impairments in motor function and coordination, evident on challenging tasks when the hypoxia was severe enough to cause brain damage, were long-lasting and described as a "hallmark of prenatal hypoxia".
Several animal studies have indicated that fetal hypoxia can affect many of the same neural substrates implicated in schizophrenia, depending on the severity and duration of the hypoxic event as well as the period of gestation, and in humans moderate or severe (but not mild) fetal hypoxia has been linked to a series of motor, language and cognitive deficits in children, regardless of genetic liability to schizophrenia. One paper restated that cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
neurological disorders were frequently found in schizophrenics and speculated hypoxia may cause the subsequent cognitive dysmetria
Whereas most studies find only a modest effect of hypoxia in schizophrenia, a longitudinal study using a combination of indicators to detect possible fetal hypoxia, such as early equivalents of Neurological Soft Signs or obstetric complications, reported that the risk of schizophrenia and other nonaffective psychoses was "strikingly elevated" (5.75% versus 0.39%). Although objective estimates of hypoxia did not account for all schizophrenic cases; the study revealed increasing odds of schizophrenia according to graded increase in severity of hypoxia.
Other factors
There is an emerging literature on a wide range of prenatal risk factors, such as prenatal stress, intrauterine (in the womb) malnutrition, and prenatal infection. Increased paternal agePaternal age effect
The paternal age effect can refer to the statistical relationships of: a man's age to sperm and semen abnormalities; a man's age to his fertility; a man's age to adverse pregnancy outcomes in his female partner ; a father's age at the birth of his offspring on the probability of an adverse...
has been linked to schizophrenia, possibly due to "chromosomal aberrations and mutations of the aging germline." Maternal-fetal rhesus or genotype incompatibility has also been linked, via increasing the risk of an adverse prenatal environment. Also, in mothers with schizophrenia, an increased risk has been identified via a complex interaction between maternal genotype, maternal behavior, prenatal environment and possibly medication and socioeconomic factors. References for many of these environmental risk factors have been collected in an online database.
There may be an association between celiac disease (gluten
Gluten
Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...
intolerance) and schizophrenia in a small proportion of patients, though large randomized controlled trials and epidemiological
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
studies will be needed before such an association can be confirmed. Withdrawal of gluten from the diet is an inexpensive measure which may improve the symptoms in a small (≤3%) number of schizophrenic patients.
In addition, there is some evidence that exposure to toxins such as lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
can also increase the risk of later development of schizophrenia spectrum disorders.
Infections
Numerous viral infections, in utero or in childhood, have been associated with an increased risk of later developing schizophrenia. Schizophrenia is somewhat more common in those born in winter to early spring, when infections are more common.Influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
has long been studied as a possible factor. A 1988 study found that individuals who were exposed to the Asian flu as second trimester fetuses were at increased risk of eventually developing schizophrenia. This result was corroborated by a later British study of the same pandemic, but not by a 1994 study of the pandemic in Croatia. A Japanese study also found no support for a link between schizophrenia and birth after an influenza epidemic.
Polio, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, varicella-zoster, rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
, herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
virus type 2, maternal genital infections, Borna disease virus
Borna disease
Borna disease is an infectious neurological syndrome of warm-blooded animals, caused by Borna disease virus, which causes abnormal behaviour and fatality....
, and more recently Toxoplasma gondii
Toxoplasma gondii
Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals . Toxoplasmosis, the disease of which T...
, have been correlated with the later development of schizophrenia. Psychiatrists E. Fuller Torrey
E. Fuller Torrey
Edwin Fuller Torrey, M.D. , is an American psychiatrist and schizophrenia researcher. He is Executive Director of the Stanley Medical Research Institute and founder of the Treatment Advocacy Center , a nonprofit organization with the goals of eliminating legal and clinical obstacles to the...
and R.H. Yolken have hypothesized that the latter, a common parasite in humans, contributes to some, if not many, cases of schizophrenia.
In a meta-analysis of several studies, they found moderately higher levels of Toxoplasma antibodies in those with schizophrenia and possibly higher rates of prenatal or early postnatal exposure to Toxoplasma gondii, but not acute infection. However, in another study of postmortem brain tissue, the authors have reported equivocal or negative results, including no evidence of herpes virus or T. gondii involvement in schizophrenia.
There is some evidence for the role of autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
in the development of some cases of schizophrenia. A statistical correlation has been reported with various autoimmune diseases and direct studies have linked dysfunctional immune status to some of the clinical features of schizophrenia.
This is known as the pathogenic theory of schizophrenia or germ theory of schizophrenia. It is a pathogenic theory of disease in which it is thought that a proximal cause of certain cases of 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...
is the interaction of the developing fetus with pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s such as virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, or with antibodies from the mother created in response to these pathogens (in particular, Interleukin 8
Interleukin 8
Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies...
). Substantial research suggests that exposure to certain illnesses (e.g., influenza) in the mother of the neonate (especially at the end of the second trimester) causes defects in neural development which may emerge as a predisposition to schizophrenia around the time of puberty, as the brain grows and develops.
Childhood antecedents
In general, the antecedents of schizophrenia are subtle and those who will go on to develop schizophrenia do not form a readily identifiable subgroup - which would lead to identification of a specific cause. Average group differences from the norm may be in the direction of superior as well as inferior performance. Overall, birth cohort studies have indicated subtle nonspecific behavioral features, some evidence for psychotic-like experiences (particularly hallucinations), and various cognitive antecedents. There have been some inconsistencies in the particular domains of functioning identified and whether they continue through childhood and whether they are specific to schizophrenia.A prospective study found average differences across a range of developmental domains, including reaching milestones of motor development at a later age, having more speech problems, lower educational test results, solitary play preferences at ages four and six, and being more socially anxious at age 13. Lower ratings of the mother's skills and understanding of the child at age 4 were also related.
Some of the early developmental differences were identified in the first year of life in a study in Finland, although generally related to psychotic disorders rather than schizophrenia in particular. The early subtle motor signs persisted to some extent, showing a small link to later school performance in adolescence. An earlier Finnish study found that childhood performance of 400 individuals diagnosed with schizophrenia was significantly worse than controls on subjects involving motor co-ordination (sports and handcrafts) between ages 7 and 9, but there were no differences on academic subjects (contrary to some other IQ findings). (Patients in this age group with these symptoms were significantly less likely to progress to high school, despite academic ability)
However, reanalysis of the data from the later Finnish study, on older children (14 to 16) in a changed school system, using narrower diagnostic criteria and with less cases but more controls, did not support a significant difference on sports and handicraft performance. However, another study found that unusual motor coordination scores at 7 years of age were associated in adulthood with both those with schizophrenia and their unaffected siblings, while unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status.
A birth cohort study in New Zealand found that children who went on to develop schizophreniform disorder
Schizophreniform disorder
Schizophreniform disorder is a mental disorder diagnosed when symptoms of schizophrenia are present for a significant portion of the time within a one-month period, but signs of disruption are not present for the full six months required for the diagnosis of schizophrenia.The symptoms of both...
had, as well as emotional problems and interpersonal difficulties linked to all adult psychiatric outcomes measured, significant impairments in neuromotor, receptive language, and cognitive development. A retrospective study found that adults with schizophrenia had performed better than average in artistic subjects at ages 12 and 15, and in linguistic and religious subjects at age 12, but worse than average in gymnastics at age 15.
Some small studies on offspring of individuals with schizophrenia have identified various neurobehavioral deficits, a poorer family environment and disruptive school behaviour, poor peer engagement, immaturity or unpopularity or poorer social competence and increasing schizophrenic symptomology emerging during adolescence.
A minority "deficit syndrome" subtype of schizophrenia is proposed to be more marked by early poor adjustment and behavioral problems, as compared to non-deficit subtypes.
Substance use
The relationship between schizophrenia and drug use is complex, meaning that a clear causal connection between drug use and schizophrenia has been difficult to tease apart. There is strong evidence that using certain drugs can trigger either the onset or relapse of schizophrenia in some people. It may also be the case, however, that people with schizophrenia use drugs to overcome negative feelings associated with both the commonly prescribed antipsychotic medication and the condition itself, where negative emotion, paranoiaParanoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...
and anhedonia
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....
are all considered to be core features.
The rate of substance use is known to be particularly high in this group. In a recent study, 60% of people with schizophrenia were found to use substances and 37% would be diagnosable with a substance use disorder.
Cannabis
There is some evidence that cannabisCannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
use can contribute to schizophrenia. Some studies suggest that cannabis is neither a sufficient nor necessary factor in developing schizophrenia, but that cannabis may significantly
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
increase the risk of developing schizophrenia and may be, among other things, a significant causal factor. Nevertheless, some previous research in this area has been criticised as it has often not been clear whether cannabis use is a cause or effect of schizophrenia. To address this issue, a recent review of studies from which a causal contribution to schizophrenia can be assessed has suggested that cannabis statistically doubles the risk of developing schizophrenia on the individual level, and may, assuming a causal relationship, be responsible for up to 8% of cases in the population.
An older longitudinal study
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...
, published in 1987, suggested a sixfold increase of schizophrenia risks for high consumers of cannabis (use on more than fifty occasions) in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
.
Despite increases in cannabis consumption in the 1960s and 1970s in western society, rates of psychotic disorders such as schizophrenia remained relatively stable over time.
Also, Sweden and Japan, where self-reported marijuana use is very low, do not have lower rates of psychosis than the U.S. and Canada do. Thus, there remains controversy over whether or not the apparent association between cannabis and schizophrenia is a causal relationship.
Amphetamines and other stimulants
As amphetamines trigger the release of dopamine and excessive dopamine function is believed to be responsible for many symptoms of schizophrenia (known as the dopamine hypothesis of schizophreniaDopamine hypothesis of schizophrenia
The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model attributing symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have...
), amphetamines may worsen schizophrenia symptoms. In addition, amphetamines are known to cause a stimulant psychosis in otherwise healthy individuals that superficially resembles schizophrenia, and may be misdiagnosed as such by some healthcare professionals.
Hallucinogens
Drugs such as ketamineKetamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
, PCP
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
, and LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
have been used to mimic schizophrenia for research purposes. Using LSD and other psychedelics as a model has now fallen out of favor with the scientific research community, as the differences between the drug induced states and the typical presentation of schizophrenia have become clear. The dissociatives ketamine and PCP, however, are still considered to produce states that are remarkably similar however, and are considered to be even better models than stimulants since they produce both positive and negative symptoms.
Tobacco use
People with schizophrenia tend to smoke significantly more tobacco than the general population. The rates are exceptionally high amongst institutionalized patients and homeless people. In a UK census from 1993, 74% of people with schizophrenia living in institutions were found to be smokers. A 1999 study that covered all people with schizophrenia in NithsdaleNithsdale
Nithsdale , also known by its anglicised gaelic name Strathnith or Stranit, is the valley of the River Nith in Scotland, and the name of the region...
, Scotland
Scotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
found a 58% prevalence rate of cigarette smoking, to compare with 28% in the general population. An older study found that as much as 88% of outpatients with schizophrenia were smokers.
Despite the higher prevalence of tobacco smoking, people diagnosed with schizophrenia have a much lower than average chance of developing and dying from lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
. While the reason for this is unknown, it may be because of a genetic resistance to the cancer, a side effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer.
A 2003 study of over 50,000 Swedish
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
conscripts found that there was a small but significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
protective effect of smoking cigarettes on the risk of developing schizophrenia later in life. While the authors of the study stressed that the risks of smoking far outweigh these minor benefits, this study provides further evidence for the 'self-medication
Self-medication
Self-medication is a term used to describe the use of drugs or other self-soothing forms of behavior to treat untreated and often undiagnosed mental distress, stress and anxiety, including mental illnesses and/or psychological trauma...
' theory of smoking in schizophrenia and may give clues as to how schizophrenia might develop at the molecular level. Furthermore, many people with schizophrenia have smoked tobacco products long before they are diagnosed with the illness, and a cohort study of Israeli conscripts found that healthy adolescent smokers were more likely to develop schizophrenia in the future than their nonsmoking peers.
It is of interest that cigarette smoking affects liver function such that the antipsychotic drugs used to treat schizophrenia are broken down in the blood stream more quickly. This means that smokers with schizophrenia need slightly higher doses of antipsychotic drugs in order for them to be effective than do their non-smoking counterparts.
The increased rate of smoking in schizophrenia may be due to a desire to self-medicate with nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
. One possible reason is that smoking produces a short term effect to improve alertness and cognitive functioning in persons who suffer this illness. It has been postulated that the mechanism of this effect is that people with schizophrenia have a disturbance of nicotinic receptor functioning which is temporarily abated by tobacco use. However, some researchers have questioned whether self-medication is really the best explanation for the association.
A study from 1989 and a 2004 case study show that when haloperidol is administered, nicotine limits the extent to which the antipsychotic increases the sensitivity
Stimulus (physiology)
In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....
of the dopamine 2 receptor. Dependent on the dopamine system, symptoms of Tardive Dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
are not found in the nicotine administered patients despite a roughly 70% increase in dopamine receptor activity, but the controls have more than 90% and do develop symptoms.A 1997 study showed that akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
was significantly reduced upon administration of nicotine when the akathisia was induced by antipsychotics. This gives credence to the idea tobacco could be used to self medicate by limiting effects of the illness, the medication, or both.
Social adversity
The chance of developing schizophrenia has been found to increase with the number of adverse social factors (e.g. indicators of socioeconomic disadvantage or social exclusionSocial exclusion
Social exclusion is a concept used in many parts of the world to characterise contemporary forms of social disadvantage. Dr. Lynn Todman, director of the Institute on Social Exclusion at the Adler School of Professional Psychology, suggests that social exclusion refers to processes in which...
) present in childhood. Stressful life events generally precede the onset of schizophrenia. A personal or recent family history of migration is a considerable risk factor for schizophrenia, which has been linked to psychosocial adversity, social defeat from being an outsider, racial discrimination, family dysfunction, unemployment
Unemployment
Unemployment , as defined by the International Labour Organization, occurs when people are without jobs and they have actively sought work within the past four weeks...
and poor housing conditions. Unemployment and early separation from parents are some important factors which are responsible for the higher rates of schizophrenia among British African Caribbean, in comparison to native African Caribbean. This is an example which shows that social disadvantage plays an equally major hand in onset schizophrenia as genetics.
Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life. Recent large-scale general population studies indicate the relationship is a causal one, with an increasing risk with additional experiences of maltreatment, although a critical review suggests conceptual and methodological issues require further research. There is some evidence that adversities may lead to cognitive biases and/or altered dopamine neurotransmission, a process that has been termed "sensitization".
Specific social experiences have been linked to specific psychological mechanisms and psychotic experiences in schizophrenia. In addition, structural neuroimaging studies of victims of sexual abuse and other traumas have sometimes reported findings similar to those sometimes found in psychotic patients, such as thinning of the corpus callosum, loss of volume in the anterior cingulate cortex, and reduced hippocampal volume.
Urbanicity
A particularly stable and replicable finding has been the association between living in an urbanUrbanization
Urbanization, urbanisation or urban drift is the physical growth of urban areas as a result of global change. The United Nations projected that half of the world's population would live in urban areas at the end of 2008....
environment and the development of schizophrenia, even after factors such as 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...
, ethnic group
Ethnic group
An ethnic group is a group of people whose members identify with each other, through a common heritage, often consisting of a common language, a common culture and/or an ideology that stresses common ancestry or endogamy...
and size of social group have been controlled for. A recent study of 4.4 million men and women in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
found a 68%–77% increased risk of diagnosed 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"...
for people living in the most urbanized environments, a significant proportion of which is likely to be described as schizophrenia.
The effect does not appear to be due to a higher incidence of obstetric complications in urban environments. The risk increases with the number of years and degree of urban living in childhood and adolescence, suggesting that constant, cumulative, or repeated exposures during upbringing occurring more frequently in urbanized areas are responsible for the association.
Various possible explanations for the effect have been judged unlikely based on the nature of the findings, including infectious causes or a generic
Generic
Generic or Generics may refer to:* Generic mood, a grammatical mood used to make generalized statements like Snow is white* Generic antecedents, referents in linguistic contexts, which are classes...
stress effect. It is thought to interact with genetic dispositions and, since there appears to be nonrandom variation even across different neighborhoods, and an independent association with social isolation, it has been proposed that the degree of "social capital" (e.g. degree of mutual trust, bonding and safety in neighborhoods) can exert a developmental impact on children growing up in these environments.
Close relationships
Evidence is consistent that negative attitudes from others increase the risk of schizophrenia relapse, in particular critical comments, hostility, authoritarian, and intrusive or controlling attitudes (termed 'high expressed emotion' by researchers). Although family members and significant others are not held responsible for schizophrenia - the attitudes, behaviors and interactions of all parties are addressed - unsupportive dysfunctional relationships may also contribute to an increased risk of developing schizophrenia. Social support systems are very important for schizophrenics and the people with whom they are in relationships.Other proposed etiologies
Psychiatrists R. D. Laing, Silvano ArietiSilvano Arieti
Silvano Arieti was a psychiatrist regarded in his time as one of the world’s foremost authorities on schizophrenia. He received his M.D. from the University of Pisa but left Italy soon after because of Benito Mussolini's increasingly racial policies...
, Theodore Lidz
Theodore Lidz
Theodore Lidz was an American psychiatrist best known for his articles and books on the causes of schizophrenia and on psychotherapy with schizophrenic patients...
and others have argued that the symptoms of what is called mental illness are comprehensible reactions to impossible demands that society and particularly family life places on some sensitive individuals. Laing, Arieti and Lidz were notable in valuing the content of psychotic
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"...
experience as worthy of interpretation, rather than considering it simply as a secondary and essentially meaningless marker of underlying psychological or neurological distress. Laing described eleven case studies of people diagnosed with schizophrenia and argued that the content of their actions and statements was meaningful and logical in the context of their family and life situations.
In 1956, Gregory Bateson
Gregory Bateson
Gregory Bateson was an English anthropologist, social scientist, linguist, visual anthropologist, semiotician and cyberneticist whose work intersected that of many other fields. He had a natural ability to recognize order and pattern in the universe...
and his colleagues Paul Watzlawick
Paul Watzlawick
Paul Watzlawick was an Austrian-American psychologist and philosopher. A theoretician in communication theory and radical constructivism, he has commented in the fields of family therapy and general psychotherapy...
, Donald Jackson
Donald deAvila Jackson
Don D. Jackson was an American psychiatrist best known for his pioneering work in family therapy.From 1947 to 1951 he studied under Harry Stack Sullivan....
, and Jay Haley
Jay Haley
Jay Douglas Haley was one of the founding figures of brief and family therapy in general and of the strategic model of psychotherapy, and he was one of the more accomplished teachers, clinical supervisors, and authors in these disciplines.-Life and works:Conceived in a log cabin on his family's...
articulated a theory of schizophrenia, related to Laing's work, as stemming from double bind
Double bind
A double bind is an emotionally distressing dilemma in communication in which an individual receives two or more conflicting messages, in which one message negates the other. This creates a situation in which a successful response to one message results in a failed response to the other , so that...
situations where a person receives different or contradictory messages. Madness was therefore an expression of this distress and should be valued as a cathartic
Catharsis
Catharsis or katharsis is a Greek word meaning "cleansing" or "purging". It is derived from the verb καθαίρειν, kathairein, "to purify, purge," and it is related to the adjective καθαρός, katharos, "pure or clean."-Dramatic uses:...
and transformative experience. In the books Schizophrenia and the Family and The Origin and Treatment of Schizophrenic Disorders Lidz and his colleagues explain their belief that parental behaviour can result in mental illness in children. Arieti's Interpretation of Schizophrenia won the 1975 scientific National Book Award
National Book Award
The National Book Awards are a set of American literary awards. Started in 1950, the Awards are presented annually to American authors for literature published in the current year. In 1989 the National Book Foundation, a nonprofit organization which now oversees and manages the National Book...
in the United States.
The concept of schizophrenia as a result of civilization has been developed further by psychologist Julian Jaynes
Julian Jaynes
Julian Jaynes was an American psychologist, best known for his book The Origin of Consciousness in the Breakdown of the Bicameral Mind , in which he argued that ancient peoples were not conscious....
in his 1976 book The Origin of Consciousness in the Breakdown of the Bicameral Mind; he proposed that until the beginning of historic times, schizophrenia or a similar condition was the normal state of human consciousness. This would take the form of a "bicameral mind" where a normal state of low affect, suitable for routine activities, would be interrupted in moments of crisis by "mysterious voices" giving instructions, which early people characterized as interventions from the gods. Researchers into shamanism have speculated that in some cultures schizophrenia or related conditions may predispose an individual to becoming a shaman; the experience of having access to multiple realities is not uncommon in schizophrenia, and is a core experience in many shamanic traditions. Equally, the shaman may have the skill to bring on and direct some of the altered states of consciousness
Altered state of consciousness
An altered state of consciousness , also named altered state of mind, is any condition which is significantly different from a normal waking beta wave state. The expression was used as early as 1966 by Arnold M. Ludwig and brought into common usage from 1969 by Charles Tart: it describes induced...
psychiatrists label as illness. Psychohistorians
Psychohistory
Psychohistory is the study of the psychological motivations of historical events. It attempts to combine the insights of psychotherapy with the research methodology of the social sciences to understand the emotional origin of the social and political behavior of groups and nations, past and present...
, on the other hand, accept the psychiatric diagnoses. However, unlike the current medical model of mental disorders
Biological psychiatry
Biological psychiatry, or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics and...
they may argue that poor parenting in tribal societies causes the shaman's schizoid personalities. Commentators such as Paul Kurtz
Paul Kurtz
Paul Kurtz is a prominent American skeptic and secular humanist. He has been called "the father of secular humanism." He is Professor Emeritus of Philosophy at the State University of New York at Buffalo, having previously also taught at Vassar, Trinity, and Union colleges, and the New School for...
and others have endorsed the idea that major religious figures experienced psychosis, heard voices and displayed delusions of grandeur.
Modern clinical psychological research has indicated a number of processes which may cause or bring on episodes of schizophrenia.
A number of cognitive bias
Cognitive bias
A cognitive bias is a pattern of deviation in judgment that occurs in particular situations. Implicit in the concept of a "pattern of deviation" is a standard of comparison; this may be the judgment of people outside those particular situations, or may be a set of independently verifiable...
es and deficits have been identified. These include attribution biases in social situations, difficulty distinguishing inner speech from speech from an external source (source monitoring), difficulty in adjusting speech to the needs of the hearer, difficulties in the very earliest stages of processing visual information (including reduced latent inhibition
Latent inhibition
Latent inhibition is a technical term used in Classical conditioning. A stimulus that has not had any significance in the past takes longer to acquire meaning than a new stimulus...
), and an attentional bias
Attentional bias
Several types of cognitive bias occur due to an attentional bias. One example is when a person does not examine all possible outcomes when making a judgment about a correlation or association...
towards threats.
Some of these tendencies have been shown to worsen or appear when under emotional stress or in confusing situations. As with related neurological findings, they are not shown by all individuals with a diagnosis of schizophrenia, and it is not clear how specific they are to schizophrenia. However, the findings regarding cognitive difficulties in schizophrenia are reliable and consistent enough for some researchers to argue that they are diagnostic.
Impaired capacity to appreciate one's own and others' mental states has been reported to be the single-best predictor of poor social competence in schizophrenia, and similar cognitive features have been identified in close relatives of people diagnosed with schizophrenia.
A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, but more recent studies indicate there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations. Some theories suggest positive symptoms of schizophrenia can result from or be worsened by negative emotions, including depressed feelings and 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 feelings of vulnerability, inferiority or loneliness
Loneliness
Loneliness is an unpleasant feeling in which a person feels a strong sense of emptiness and solitude resulting from inadequate levels of social relationships. However, it is a subjective experience...
. Chronic negative feelings and maladaptive coping skills may explain some of the association between psychosocial stressors and symptomology. Critical and controlling behaviour by significant others (high expressed emotion
Expressed emotion
Expressed emotion , is a qualitative measure of the 'amount' of emotion displayed, typically in the family setting, usually by a family or care takers....
) causes increased emotional arousal and lowered self-esteem and a subsequent increase in positive symptoms such as unusual thoughts. Countries or cultures where schizotypal personalities or schizophrenia symptoms are more accepted or valued appear to be associated with reduced onset of, or increased recovery from, schizophrenia.
Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history, or social circumstances of the individual. Holding minority socio-cultural beliefs, for example due to ethnic background, has been linked to increased diagnosis of schizophrenia. The way an individual interprets his or her delusions and hallucinations (e.g. as threatening or as potentially positive) has also been found to influence functioning and recovery.
Some experts think autonomy vs intimacy is a motivation for schizophrenic symptoms.
Other lines of work relating to the self in schizophrenia have linked it to psychological dissociation
Dissociation
Dissociation is an altered state of consciousness characterized by partial or complete disruption of the normal integration of a person’s normal conscious or psychological functioning. Dissociation is most commonly experienced as a subjective perception of one's consciousness being detached from...
or abnormal states of awareness and identity as understood from phenomenological and other perspectives.
Psychiatrist Tim Crow
Tim Crow
Tim Crow is a British psychiatrist and researcher from Oxford. Much of his research is related to the causes of schizophrenia. He also has an interest in neurology and the evolutionary theory. He is the Honorary Director of the Prince of Wales International Centre for Research into Schizophrenia...
has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language
Language
Language may refer either to the specifically human capacity for acquiring and using complex systems of communication, or to a specific instance of such a system of complex communication...
. Since psychosis is associated with greater levels of right brain hemisphere activation and a reduction in the usual left brain hemisphere dominance, our language abilities may have evolved at the cost of causing schizophrenia when this system breaks down.
In alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
, some practitioners believe that there are a vast number of physical causes of what ends up being diagnosed as schizophrenia. While some of these explanations may stretch credulity, others (such as heavy metal poisoning and nutritional imbalances) have been supported at least somewhat by research. However, it is not entirely clear how many patients initially diagnosed with schizophrenia these alternative explanations may account for.
External links
— Support Groups - Articles and research- Schizophrenia at the National Institute of Mental HealthNational Institute of Mental HealthThe National Institute of Mental Health is one of 27 institutes and centers that make up the National Institutes of Health...