This competing renewal for an independent scientist award (1 K02 MHO 1180) seeks to further elucidate the premorbid indicators of biological risk for schizophrenia and continue scientific development of the applicant through coursework, collaborations and consultations with other scientists. The central hypothesis of the proposed study is that an abnormality in late neurodevelopmental maturation of the thalamocortical circuits underlies the vulnerability to schizophrenia. During the first funding cycle of this award, the investigator has recruited a well-characterized cohort of child and adolescent relatives of schizophrenia patients (HR-S) who show evidence of impaired structural and functional integrity of the cortical and thalamic brain structures. These impairments appear to progressively evolve during adolescence. In the proposed study he will seek to confirm these observations in an independent cohort of HR-S subjects, and to examine structural and functional integrity of cortical and the thalamic structures in the HR-S subjects by neurobehavioral, neuroimaging and P50 studies. He will also follow up the original cohort of HR-S subjects to seek evidence of continuing brain dysmaturation and its relation to emergence of psychopathology. These studies will establish a cohort of HR-S subjects for further follow-up studies of developmental vulnerability to schizophrenia. The candidate also intends to enhance his scientific development by collaborations with other clinical and neuroscience investigators at the University of Pittsburgh and at other Universities. Specifically, he seeks to further his skills in developmental neuroscience, genetics, neuroimaging as well as clinical and design issues for studies of high risk subjects. The proposed studies will facilitate the applicant's continued involvement in mentoring activities, and develop collaborations for a multi-site study of HR-S subjects proposed to be submitted in the near future. This professional enhancement plan and the research project are likely to help the candidate realize his full potential and contribute to our further understanding of the pathogenesis of schizophrenia.
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