The primary purpose of the request for this NIMH Scientist Development Award is to provide training and research experience in understanding brain-behavior relationships, in order to apply this knowledge to the development of models of schizophrenia. The focus is on the relationships between brain function and structure, as operationalized by tools in neuropsycology, behavioral neurology, and neuroanatomy. There are 4 elements to the proposal: 1) supervised training in neuropsychological assessment; 2) supervised training i neuroanatomy, including the measurement of brain structures using magnetic resonance imaging; 3) didactic seminars and course work in neuropsychology, neuroanatomy, behavioral neurology, and other basic neuroscience; and 4) supervised research experience that will apply knowledge and skills learned in training. Past research suggests that men and women may be at different risks for expressing particular forms of schizophrenia. This proposal presents a novel approach to elucidating some of the processes underlying gender differences in abnormal neurodevelopment in schizophrenia, by using dyslexia as a model. Dyslexia is a useful comparison group, since there are similarities between schizophrenia and dyslexia regarding pathological brain areas and sex effects. Thus, established findings in the literature on dyslexia may provide insights into the effect of sex on neuropsychological and cognitive deficits underlying schizophrenia. Hypotheses will be tested with 40 DSM-III-R schizophrenics and 40 normal controls, equally divided by sex, and proportionately matched on age, ethnicity and parental socioeconomic status. Patients will be randomly sampled from a large outpatient service and normal controls from the same catchment area. 40 DSM-III-R dyslexics will also be selected, matched on age, sex, ethnicity and parental SES, and sampled from 2 learning disorder outpatient clinics in the same catchment area. Variables assessed include neurodevelopmental and perinatal history, symptomatology, neurospsychological and cognitive tests, family history of psychiatric and autoimmune disorders, and structural brain imaging. Hypotheses regarding gender differences in brain structure and function focus on prefrontal and temporal lobe regions and laterality effects, which have been found to be important for understanding brain dysfunction in schizophrenia. The proposed training would extend the epidemiologic skills of the investigator into the area of neuroscience and provide a basis for a more informed perspective from which to develop models of schizophrenia.
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