In support of our second hypothesis, we find that both COS probands and their non-psychotic SIBs show a complete reversal of the relationships that exists between Val158Met genotype and CT maturation in HCs. This inversion is most pronounced in fronto-temporal sub-regions where existing cross-sectional studies in schizophrenia have found Val158Met genotype to modulate cortical structure (McIntosh et al., 2007; Ohnishi et al., 2006) and function (Prata et al., 2009) in a manner that differs from that seen in HC groups (Ohnishi et al., 2006; Prata et al., 2009). Moreover, abnormalities of structural maturation (Brans et al., 2008) and function (Fusar-Poli et al., 2007) within these same cortical regions appear to index genetic risk for schizophrenia, whether active disease is present or not. Our findings imply that shared fronto-temporal abnormalities in persons with schizophrenia and their unaffected relatives could, in part, arise due to shared disruptions of the mechanisms through which Val158Met genotype normally influences cortical development during childhood and adolescence. Because these disruptions are evident in both probands and unaffected relatives, they likely reflect shared genetic and/or environmental risk factors
