Adolescent Neural Substrates of Risk for Schizophrenia

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DESCRIPTION (provided by applicant): The principal aim of this career development plan is to provide the candidate with the training, support, and resources required to develop as an independent investigator in the field of neuropsychiatric research. The candidate's long-term goals are to advance knowledge of the developmental neuropathology of schizophrenia by establishing a multidisciplinary research program that combines epidemiologic, developmental, and neuroimaging methods. The candidate's short-term goals for the duration of this award are to develop expertise in the following areas: (1) methods, design, and analysis of magnetic resonance imaging (MRI) studies; (2) cognitive neuroscience and neuropsychology; (3) longitudinal research methods and design. These training goals will be met through a combined program of coursework, consultation with established research scientists in these fields, and completion of a research study plan at McLean Hospital's Brain Imaging Center. The design and hypotheses of the proposed study were based on a growing body of work (including the candidate's prior research) indicating that genetic and obstetric factors may disrupt brain development in a manner that predisposes to schizophrenia. There is also preliminary evidence that the characteristic timing of psychosis onset in late adolescence may relate to maturational brain changes that occur around this period in prefrontal and temporal-limbic cortices. Accordingly, the research plan proposes a longitudinal, case-control investigation of adolescents at high (HR) and low (LR) genetic risk for schizophrenia. The first major aim of the study is to examine the contributions of genetic risk status and OCs to the prediction of neuropsychological measures of cognitive function and structural MRI measures of regional brain volume. The second major aim is to assess age-related changes in brain structure and cognitive function between the baseline and 2-year follow-up assessments in the HR and LR subjects. The results of this study are expected to increase our understanding of the normative brain maturational changes of adolescence, which has been a relatively under-studied area despite its potential relevance to schizophrenia and other neuropsychiatric disorders. In addition, this study has relevance to the pathophysiology of schizophrenia and to the premorbid identification of individuals at heightened risk for the disorder.