We also find notable differences between COS and SIB groups in the regional distribution and developmental timing of disrupted relationships between Val dose and CT maturation. Differences between COS and SIB groups in the age at which CT trajectories for Val158Met genotype groups “cross-over”, would suggest that Val carriage confers persistence of dlPFC CT deficits in COS probands relative to HCs, whereas in SIBs, CT deficits resolve over the same developmental period, regardless of Val dose. This observation echoes our earlier findings that whereas both COS probands and SIBs show fronto-temporal gray matter deficits relative to HCs in early adolescence, these persist into adulthood in COS probands, but resolve over time in non-psychotic SIBs (Gogtay et al., 2003; Greenstein et al., 2006). Thus, cortical maturation in COS appears to be especially sensitive to Val dose within the PFC, in a manner that is not seen in non-psychotic SIBs. This finding is consistent with the prominent contribution of COMT to DA regulation in the PFC, and notion that PFC hypodopaminergia is more marked in people with schizophrenia and their healthy relatives (Hirvonen et al., 2006).
