fMRI Studies in Adolescents At-Risk for Schizophrenia

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DESCRIPTION (provided by applicant): The aim of this career development proposal is to allow the applicant to acquire the skills necessary to characterize neurodevelopmental abnormalities associated with adolescents at risk for schizophrenia. Schizophrenia is a highly debilitating and complex disorder marked by severe abnormalities in cognitive function, particularly working memory. The illness may be mediated by neurodevelopmental abnormalities and by genetic factors. Studies of neurodevelopment in adolescent first-degree relatives who are at significantly elevated risk for developing the illness promise to help better elucidate the premorbid diatheses of the illness. This proposal will use fMRI to investigate working memory abnormalities in adolescent first-degree relatives of schizophrenia patients. The use of fMRI will facilitate an understanding of alterations in the functional neuroarchitecture of these subjects and fill a lacuna in the present understanding of the precursors of the illness. The analysis of the fMRI data will focus on identifying regions of aberrant activation, as well as probing functional disconnections between regions of the brain. Relationships between aberrant fMRI activation and structural alterations in the brain will also be explored. During the course of this award, the applicant will obtain training in: 1) understanding developmental neuroscience during the period of adolescence, 2) the use of fMRI for the study of adolescent high-risk populations 3) understanding of the clinical issues associated with schizophrenia, particularly its premorbid and prodromal phases, 4) understanding of statistical, ethical and epidemiological issues associated with the field neuropsychiatric research. By the conclusion of the award, the applicant expects to emerge as an expert on the application of neuroimaging to the study of the neurobiological precursors of schizophrenia. The proposal's focus promises to provide better insights into the developmental neurobiology of the illness and the contributions of development and genetics. The data will help the applicant develop larger projects during the concluding years of the award period that may help in the development of psychosocial and psychopharmacologic interventions in adolescents at risk for schizophrenia.