Endophenotype is a psychiatric concept and a special kind of biomarker. The purpose of the concept is to divide behavioral symptom

Symptom

A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s into more stable phenotypes with a clear genetic

Genetics

Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 connection. The concept was originally borrowed by Gottesman & Shields from insect biology

Entomology

Entomology is the scientific study of insects, a branch of arthropodology...

.
Other terms with similar meaning but not stressing the genetic connection are "intermediate phenotype", "biological marker", "subclinical trait", "vulnerability marker", and "cognitive marker".

Definition

The accepted criteria that a biomarker must fulfill to be called an endophenotype include:

1. The endophenotype is associated with illness in the population.
2. The endophenotype is heritable.
3. The endophenotype is primarily state-independent (manifests in an individual whether or not illness is active).
4. Within families, endophenotype and illness co-segregate.

Subsequently, an additional criterion that may be useful for identifying endophenotypes of diseases that display complex inheritance patterns was suggested:

• The endophenotype found in affected family members is found in nonaffected family members at a higher rate than in the general population.

For schizophrenia

In the case 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...

, the overt symptom could be a 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"...

, but the underlying phenotypes are, for example, a lack of sensory gating

Sensory gating

Sensory gating describes neurological processes of filtering out redundant or unnecessary stimuli in the brain from all possible environmental stimuli. Also referred to as filtering, or sensorimotor gating, sensory gating prevents an overload of irrelevant information in the higher cortical...

 and a decline in working memory

Working memory

Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...

. Both of these traits have a clear genetic component and can thus be called endophenotypes. A strong candidate for schizophrenia endophenotype is prepulse inhibition

Prepulse inhibition

Prepulse Inhibition is a neurological phenomenon in which a weaker prestimulus inhibits the reaction of an organism to a subsequent strong startling stimulus . The stimuli are usually acoustic, but tactile stimuli Prepulse Inhibition (PPI) is a neurological phenomenon in which a weaker...

, the ability to inhibit the reaction to startling stimuli.

The distinct genes that could underlie certain endophenotypic traits in schizophrenia include:

• RELN
  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...
  
   – coding the reelin protein downregulated in patients' brains. In one study its variants were associated with performance in verbal and visual working memory tests in the nuclear families of the sufferers.
• FABP7
  FABP7
  Fatty acid binding protein 7, brain , is a human gene.FABP7 is expressed, during development, in radial glia by the activation of Notch receptors...
  
  , coding the Fatty acid-binding protein 7 (brain), one SNP of which was associated with schizophrenia in one study, is also linked to prepulse inhibition
  Prepulse inhibition
  Prepulse Inhibition is a neurological phenomenon in which a weaker prestimulus inhibits the reaction of an organism to a subsequent strong startling stimulus . The stimuli are usually acoustic, but tactile stimuli Prepulse Inhibition (PPI) is a neurological phenomenon in which a weaker...
  
   in mice. It is still uncertain though whether the finding will be replicated for human patients.
• 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...
  
  , coding the neuronal nicotinic acetylcholine receptor alpha7 subunit. alpha7-containing receptors are known to improve prepulse inhibition, pre-attentive and attentive states.

For suicide

The endophenotype concept has also been used in suicide

Suicide

Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

 studies. A tentative endophenotype between the phenotype of completed suicide and the genetic basis is impulsive-aggressive behaviors (IABs). The genetic basis of the trait has been suggested to be the gene coding for the serotonin

Serotonin

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

 receptor 5-HT

5-HT1B receptor

5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.-Tissue distribution and function:...

_1B, known to be relevant in aggressive behaviors.