Adida M, Azorin JM, Fakra E, Belzeaux R, Kaladjian A, Pomietto P, Corréard N
Encephale 2012 Dec;38 Suppl 3:S98-102
BACKGROUND: The term endophenotype was used by Gottesman (1991) to describe a trait that may be intermediate on the chain of causality from genes to diseases. Some family relatives of affected patients also carry the endophenotype, although not the disease phenotype. The increased penetrance of the endophenotype, and its closer relationship to the gene than that of the phenotype proper, are expected to help genetic studies. An endophenotype may be neuropathological, neurocognitive, emotional, neurophysiological or neurobiological in nature.
METHODS: We used a survey of neurobiological studies to select and evaluate endophenotype candidates for schizophrenia and for bipolar disorder.
RESULTS: Neurobiological endophenotype candidates for schizophrenia include lateral ventricles enlargement, grey matter atrophy in frontal lobe and insula, decreased levels of N-acetyl-aspartate in the hippocampus and niacin-induced flushing. Neurobiological endophenotype candidates for bipolar disorder include tryptophan depletion-induced planning impairment, abnormalities of reward system, psychostimulants-induced behavioural differences, hypersensitivity to cholinergic REM induction test and abnormalities of immune and hypothalamus-pituitary-adrenergic system.
CONCLUSIONS: More studies to evaluate endophenotype candidates with respect to specificity, heritability, temporal stability, and prevalence in unaffected relatives are encouraged in schizophrenia and bipolar disorder.