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This application is for further studies of EEG sleep in schizophrenia. The investigator's data indicate that reductions in slow wave sleep (SWS) in schizophrenia are present early in the disorder and persist during later phases of illness. He also finds that decreased SWS in schizophrenia correlates with negative symptoms, attentional impairment, relatively poor outcome and abnormal brain metabolism as evidenced by 31Phosphorous MRS (31P MRS) studies. MR studies have also revealed significant volume deficits in cortical gray matter, as well as altered membrane and energy metabolism in the prefrontal cortex in these patients. The presence of the observed alterations early in illness, the lack of a relationship with illness duration and their persistence suggest that they may be related to neurodevelopmental abnormalities. The investigator therefore hypothesizes that abnormal SWS in schizophrenia is related to developmentally-mediated pathophysiology of the association cortex and the thalamus. The overall goal of this continuation grant application is to examine EEG sleep parameters (specifically SWS), in conjunction with brain structural and metabolic data, in order to address the pathophysiological heterogeneity in schizophrenia. This application aims: 1) to confirm in a first-episode treatment-naive population, our findings of decreased SWS and metabolic and structural alterations in the association cortex and thalamus; and 2) to examine whether decreased SWS is associated with abnormal structure and metabolism in the association cortex and thalamus, with negative symptoms, cognitive and neurological impairment, poor premorbid functioning, and poor outcome in schizophrenia. The investigator also wishes to obtain preliminary data on: 1) whether schizophrenia patients have a defect in recovery of SWS, but not rapid eye movement (REM) sleep after sleep deprivation; and 2) whether decreased SWS and other proposed alterations in corticothalamic structure and metabolism are more frequently seen in "high-risk" offspring of schizophrenic parents. To address these aims, he proposes to examine 60 drug-free first-episode schizophrenic patients, 30 "high-risk" offspring of schizophrenic parents and 90 matched healthy controls and conduct sleep EEG, 31P MRS and MRI studies, neurological, neuropsychological and clinical evaluations. The hypotheses in this study, if confirmed, will contribute to progress toward a neurodevelopmental classification of schizophrenia as well as toward a better understanding of vulnerability to this enigmatic illness.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.