Schizophrenia is associated with subtle abnormalities of brain structure on MRI, including enlargedlateral ventricles, reduced cortical gray matter volumes, reduced hippocampal volumes, as well as abnormaldiffusion properties in white matter. While it has been hypothesized that these brain abnormalities ariseduring early brain development, there has been little direct evidence to support this idea. In the first fundingperiod of this Conte Center project, we developed the magnetic resonance image (MRI) acquisition andimage analysis tools to study very early brain development in children at high risk for schizophrenia. Theseincluded a genetic high risk group - the offspring of women with schizophrenia, and a 'structural' high riskgroup - children with prenatal isolated mild ventriculomegaly. Our results to data indicate that compared tonormal controls, the offspring of mothers with schizophrenia have reduced cortical gray matter volumes onneonatal MRI. This is the first concrete evidence that early cortical development is compromised by geneticvulnerability. The perinatal and early postnatal period is one of the critical periods in the development ofcortical connectivity - a time of rapid synapse growth - one that is a focus of this Conte Center. In addition,we have developed a large cohort of normal controls. In the second funding period, we propose to continueour study of every early brain development in normal and high risk children, applying our novel imageanalysis methodologies to study gray and white matter development in an expanding cohort, and to studylongitudinal brain developmental changes as we follow our cohort into mid childhood. Specifically we willstudy longitudinal brain development in children at high risk for schizophrenia with 3T MRI (includingdiffusion tensor imaging) and neurodevelopmental assessments at ages 0, 1, 2, 4, and 6 years of age. Wewill also study early brain development in the offspring of mothers with bipolar illness as a comparison groupfor non-specific effects of medication and chronic illness. Finally, we have obtained DMA and MRIs on alarge group of normal neonates and will determine if polymorphisms of risk genes influence corticaldevelopment at this earliest stage of life.
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