Endophenotype

Endophenotype is a psychiatric concept and a special kind of biomarker. The purpose of the concept is to divide behavioral symptoms into more stable phenotypes with a clear genetic connection. The concept was originally borrowed by Gottesman & Shields from insect biology. 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] [2]}

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. ^[3]

For schizophrenia

In the case of schizophrenia, the overt symptom could be a psychosis, but the underlying phenotypes are, for example, a lack of sensory gating and a decline in working memory. Both of these traits have a clear genetic component and can thus be called endophenotypes.^[2] A strong candidate for schizophrenia endophenotype is prepulse inhibition, the ability to inhibit the reaction to startling stimuli.

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

• RELN – 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.^[4]
• FABP7, coding the Fatty acid-binding protein 7 (brain), one SNP of which was associated with schizophrenia in one study,^[5] is also linked to prepulse inhibition in mice.^[5] It is still uncertain though whether the finding will be replicated for human patients.
• CHRNA7, coding the neuronal nicotinic acetylcholine receptor alpha7 subunit. alpha7-containing receptors are known to improve prepulse inhibition, pre-attentive and attentive states.^[6]

For suicide

The endophenotype concept has also been used in suicide 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 receptor 5-HT_1B, known to be relevant in aggressive behaviors.^[7]

See also

• Biomarker

References