The long-range goal of the proposed Center is to provide a neurobiological framework for understanding and ultimately treating or preventing the cardinal features of schizophrenia. The underlying hypothesis is that the disordered thought processes and affective responses in schizophrenia reflect deficient information processing and regulatory mechanisms of specificable cortico- cortical and subcortical circuits involving premarily but not exclusively the prefrontal cortex. A relationship between the prefrontal cortex and schizophrenia was evident to scientists and clincians from the early part of this century and the evidence has grown more compelling with advances in neuroscience and medicine. A team of investigators from different departments and disciplines spanning six institutions (Yale, Harvard, McLean Hospital, West Haven VA, Salpetriere, Pasteur Institute) have joined together in this effort. Six projects include 1) single cell recordings in normal rhesus monkeys performing tasks that tap psychological processes hypothesized to be relevant to schizophrenia; 2) the study of eye tracking and cognitive deficits in schizophrenic patients and nonhuman primates with prefrontal cortical lesions to identify common elements of the disorder and their cortical localization; 3) cytological and immunohistochemical analysis at the light and electronmicroscopic level of schizophrenic cortex aimed at identifying structural or biochemical lesions in specific pathways; 4) comparative receptor autoradiographic analysis of D1, D2, CCK and 5-HT receptors in selected cortical areas of the schizophrenic and nonhuman primate brain; 5) behavioral, dialysis and receptor-autoradiographic studies of primate models which address selective symptoms of schizophrenic, e.g., amphetamine- induced """"""""psychosis"""""""" or precipitating conditions, e.g., pharmacological depletion of dopamine and stress effects in adult rhesus monkey and their dependence on prefrontal cortex, and 6) developmental induction of an animal model with selective deletion of specifiable cortico-cortical elements that are hypothesized to be essential for the information-processing circuits deemed to be important in schizophrenia. This Center represents a multidisciplinary, comparative initiative to uncover the biological foundations of schizophrenia combining advanced neurobiological, neuropsychological, and molecular techniques, intertwined and supported by a strong theoretical base and testable hypotheses.
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