To link a gene effect in brain to the gene effect on risk for the syndromal diagnosis, it is necessary to show that the brain effect is a biological substrate also linked to illness risk, a so called intermediate phenotype. An intermediate phenotype related to mental illness is a heritable trait that is located in the path of pathogenesis from genetic predisposition to psychopathology [12]. The path goes from relatively simple effects in cells, to more complex effects in neural circuits in the brain, to much more complex effects on the emergent phenomenology of these simpler effects, i.e. behavior and psychiatric syndromes (see Figure 1A).
