This proposal is designed to elucidate the antecedents and neurobehavioral sequelae of adult schizophrenia and spectrum disorders. A high-risk sample will be selected, for whom pre-and perinatal complications (PPCs) were prospectively measured, and cognitive, neurologic and behavioral measures were administered at multiple points up to age 7. The central goal of the study is to determine the relative influence of genetic predisposition and PPCs on diagnosis, symptoms and neuropsychological function in schizophrenia and spectrum disorder, and to assess the specificity of such factors by comparing offspring of schizophrenics with offspring of affective psychotics and normal controls. The study sample will be drawn from the Providence and Boston cohorts of the National Collaborative Perinatal Project (NCPP) and builds on previous work by our group that has demonstrated the feasibility of such a project. Previous research has indicated a role for PPCs in the development of schizophrenia. Due to problems of accessibility of data, pregnancy complication, the subset of PPCs that may be most relevant to schizophrenia, have received far less attention than other complications that are more easily assessed. We intend to relate chronic hypoxia, maternal viral infections and autoimmune disturbance during pregnancy, as well as other classes of PPCs, to behavior and neuropsychological function at age 7 and in adulthood. This proposal requests funds to complete the second half of a 6-year project. By the completion of Phase I (year 1-3), we will have identified all NCPP parents with a history of psychiatric treatment or hospitalization, located and recruited 629 potential index subjects, and conducted a two-stage diagnostic interview protocol that will identify approximately 200 parents with a history of psychosis. The same number of comparison parent subjects, matched for parent and offspring gender, age, ethnicity, site, and history of PPCs, will complete a similar protocol. Preliminary analyses described herein will be completed and will determine the independent and interactive effects of a genetic predisposition for schizophrenia and PPCs on neurobehavioral deficits through age 7 (neuropsychological, cognitive, behavioral, and neurological function). In Phase II (current application), we will locate and recruit approximately 80% of the 600 NCPP offspring of this parent sample, now age 30-36. A two-component assessment will assess a) psychiatric symptoms and diagnoses, including positive and negative symptoms; and b) neuropsychological function, including attention, abstraction, executive function, verbal and visual learning and memory, language, visual-spatial, and motor skills. With these data we will extend the Phase I analyses and determine the relative risk for adult psychiatric symptomatology (diagnosis) and neuropsychological deficits associated with genetic predisposition, PPCs or both. This will be the first community study with systematic assessments of PPC beginning early in pregnancy, parental psychopathology, and neuropsychological and psychiatric function of adult offspring through the peak ages of risk for the onset of psychosis. The results should be of great scientific relevance, with immediately clinical and research implications.
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