The investigators are proposing a 5-year competing continuation study to test the hypothesis that one's sex modifies brain volume abnormalities in schizophrenia (SCZ) in areas that are normally sexually dimorphic and places males at higher risk for more severe cognitive consequences than females with SCZ. Based on preliminary findings in MH56956 and others' work, they predict that males and females will differ in volumetric reductions in specific cortical regions and their associated areas in the corpus callosum, differences will contribute to explaining more severe verbal learning/memory deficits in males. Further predictions that these """"""""sex-specific """""""" cortical reductions in SCZ will more likely be associated with prenatal insults than with peri/postnatal insults. Finally, we will test whether prenatal insults result in similar sex-specific cortical volumetric reductions in subjects with SCZ compared with affective psychoses. A unique opportunity to test the hypotheses using subjects who were originally ascertained from a community sample of pregnancies from the Providence and Boston cohorts of the National Collaborative Perinatal Project (NCPP). Pregnancies were followed prospectively, bloods were drawn from mothers, and the children were regularly evaluated up to age 7. Serologic assays of exposures are currently being conducted at no cost to this proposal. From the NCPP sample, the investigators have been conducting a case-control study, in which they will have systematically located, recruited and diagnosed 123 DSM-IV psychotic cases, approximately 60 percent with SCZ and 40 percent with affective psychoses, who are now 3340 years of age. Subjects and their parents are evaluated clinically, and family history information (i.e. potential genetic vulnerability) is obtained. Cases are individually matched to normal controls based on age, sex, ethnicity, study site, and history of obstetric insults. In the proposed study, expectations to successfully reascertain 105 of these cases and 105 matched controls to conduct structural magnetic resonance imaging (MRI) and a cognitive battery focused on the components of verbal learning/memory. The investigators are using a sophisticated parcellation technique of MR scans that reliably identifies gray and white matter in cortical and subcortical regions. The tests of the hypotheses will provide us with knowledge about the relationships between brain morphology and cognition in SCZ, how one's sex may modify these relationships, the potential role of the timing of insults in producing these abnormalities, and whether the impact of sex is disease-specific or shared by another illness, suggesting some robust properties of the normal female and male brain in the face of disease.
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