Since DA is known to influence cellular processes fundamental to structural development of the cortex (Bhide, 2009), inherited disruptions of DA signaling could contribute to the cortical dysmaturation that has been reported in people with schizophrenia during adolescence and early adulthood (Greenstein et al., 2006; Thompson et al., 2001; Vidal et al., 2006), and is also seen in non-psychotic siblings of probands in an attenuated form (Gogtay et al., 2007). We sought to test this notion by relating a genetic variant that impacts DA signaling, to cortical maturation in a large, longitudinally scanned sample of healthy controls (HCs), individuals with childhood-onset schizophrenia (COS) and the non-psychotic siblings (SIBs) of COS probands. Specifically, we hypothesized that a functional polymorphism within the gene encoding the DA catabolizing enzyme catechol-o-methyltransferase [COMT Val158Met single nucleotide polymorphism (SNP)] would modulate cortical maturation in HCs, but that these normative gene–brain relationships would be disrupted in patients with COS. We also studied the unaffected SIBs of COS probands as a way to test if any observed alterations of gene–brain relationships in COS patients reflected the consequences of
