Chunk #118 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.1. Intermediate phenotypes, or “endophenotypes”
A number of criteria for psychophysiological endophenotypes were proposed (de Geus, 2002, 2010), including 1) association with disorder, even during remission; 2) temporal stability including developmental stability; 3) heritability; 4) familial association with disorder as indicated by the presence of the same abnormality in the first degree relatives of probands. Additional criteria may include a) association with dimensional phenotypes indicating liability such as temperamental traits, for example, harm avoidance and trait negative affect for internalizing spectrum disorders and impulsivity for externalizing spectrum; b) suitability for repeated administration, i.e. relative resistance to learning and practice effects; c) availability of animal models, which allows for a more detailed investigation of both genetic and neurobiological mechanisms at more elementary levels such as gene expression in specific brain regions and its modification by strictly controlled environmental influences and neurophysiological investigation and the level of single neurons and local circuits; d) construct validity in the sense that psychophysiological measure is a specific and valid indicator for a certain cognitive process; e) knowledge of the underlying genetic architecture and specific genes involved, i.e. heritability “explained”.
