The diagnostic specificity of these GM trajectories was established by comparing individuals with COS with a longitudinally scanned group of children with atypical psychosis with similar initial presentation but ruled out from having schizophrenia after an extensive evaluation including complete medication washout (Kumra et al., 1998). At 2-10 year follow-up, none of these children had converted to meeting diagnostic criteria for schizophrenia, but a surprising 40% of them were later diagnosed with Bipolar I disorder. The developmental trajectories for these children showed a subtle but very distinct pattern of cortical GM gain in left temporal cortex and GM loss in right temporal and subgenual cingulate cortices, a pattern that has no overlap with the pattern seen for COS (Gogtay, Ordonez et al., 2007). As seen in Figure 3, these observations, which establish the diagnostic specificity of the GM findings, also suggest that the GM changes are unlikely to be attributable to medication effects, as the bipolar group had been treated with similar medications (Gogtay, Ordonez et al., 2007; Gogtay, Sporn et al., 2004). The familial/genetic nature of these abnormal changes is further supported by studies of healthy siblings discussed below.
