Endophenotype
In
The next major use of the term was in
Definition
In psychiatry research, the accepted criteria which a biomarker must fulfill to be called an endophenotype include:[5][16][17]
- An endophenotype must segregate with illness in the population.
- An endophenotype must be heritable.
- An endophenotype must not be state-dependent (i.e., manifests whether illness is active or in remission).
- An endophenotype must co-segregate with illness within families.
- An endophenotype must be present at a higher rate within affected families than in the population.
- An endophenotype must be amenable to reliable measurement, and be specific to the illness of interest.
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.[5] A strong candidate for schizophrenia endophenotype is prepulse inhibition, the ability to inhibit the reaction to startling stimuli.[18] However, several other task-related candidate endophenotypes have been proposed for schizophrenia,[19] and even resting measures extracted from EEG, such as, power of frequency bands[20] and EEG microstates.[21]
Endophenotypes are quantitative, trait-like deficits that are typically assessed by laboratory-based methods rather than by clinical observation.
The four primary criteria for an endophenotype are that it is present in
Some distinct genes that could underlie certain endophenotypic traits in schizophrenia include:
- RELN – coding the reelin protein downregulated in patients' brains. In one 2008 study, its variants were associated with performance in verbal and visual working memory tests in the nuclear families of patients.[24]
- FABP7, coding the Fatty acid-binding protein 7 (brain), one SNP of which was associated with schizophrenia in one 2008 study,[25] is also linked to prepulse inhibition in mice.[25] 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.[26]
For bipolar disorder
In
For suicide
The endophenotype concept has also been used in suicide studies. Personality characteristics can be viewed as endophenotypes that may exert a diathesis effect on an individual's susceptibility to suicidal behavior. Although the exact identification of these endophenotypes is controversial, certain traits such as impulsivity and aggression are commonly cited risk factors.[29] One such genetic basis for one of these at-risk endophenotypes has been suggested in 2007 to be the gene coding for the serotonin receptor 5-HT1B, known to be relevant in aggressive behaviors.[30]
See also
References
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Kendler, K S; Neale, M C (2010-08-15). "Endophenotype: a conceptual analysis". Molecular Psychiatry. 15 (8): 789–797. PMID 20142819.
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