Gottesman’s definition of an endophenotype is that it should be heritable, co-segregate with a psychiatric illness, yet be present even when the disease is not (i.e. state independent), and be found in non-affected family members at a higher rate than in the population (Gottesman & Gould, 2003). The criterion of state independence was modified to take into account the importance of epigenetic and developmental factors so that the endophenotype can be manifest only at a certain age and/or after a challenge (in the same way that a glucose challenge is used for a glucose tolerance test) (Hasler et al. 2006). Others have added criteria that require endophenotypes to be part of the causal process by which disease arises (Lavori et al. 2002), or at least be involved in a biologically plausible mechanism of pathogenesis (Tsuang et al. 1993; Castellanos & Tannock, 2002), or, following Almasy & Blangero (2001), require that an endophenotype ‘should be continuously quantifiable, should predict disorder probabilistically and should be closer to the site of primary causative agent (whether genetic or environmental) than to diagnostic categories’. It
