Schizophrenia risk to onset: Neurobiology and prevention

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DESCRIPTION (provided by applicant): This revised application for a Mentored Patient-Oriented Research Career Development Award (K23) presents a plan for Dr. Cheryl Corcoran to pursue training and research in the prospective assessment of the schizophrenia prodrome, specifically risk factors, intervening variables and markers associated with the onset of psychosis. The goals of the training and research plan are integrated around the hypothesis that the neural diathesis of schizophrenia liability involves a vulnerability to develop psychosis in the context of psychosocial stress. Dr. Corcoran currently has experience in studying 1) the schizophrenia prodrome and 2) stress exposure and its correlates in schizophrenia. Under the sponsorship of Dr. Malaspina, and drawing upon resources at both NYSPI/Columbia and Hillside Hospital, Dr. Corcoran's training plan combines formal coursework and direct supervision with clinical research experience and training. Dr. Corcoran has established a prodromal research clinic at NYSPI, entitled the "Center of Prevention and Evaluation" (COPE). The training plan involves 1) clinical methodologies in the assessment of stress and the HPA axis in schizophrenia (Malaspina); 2) increased expertise in prodromal research and neuropsychology (Cornblatt); 3) data analysis in longitudinal studies (Begg) and 4) adolescent cognitive and social development (Kestenbuam). The research plan is a prospective cohort study of prodromal patients that employs clinical methodologies that probe HPA axis function, prodromal symptoms, and psychosocial stress exposure. The hypotheses are that baseline stress-reactivity (stress reactive cortisol and impaired tolerance to normal stress) and intervening life events will increase risk for psychosis in prodromal patients. Important covariates are also evaluated, including cognition, early trauma, and medication and substance use. This study will provide the applicant with the knowledge and research experience necessary to apply for an R01 to further evaluate risk factors, mediators and markers of psychosis onset in prodromal patients.