Certain physiological and cognitive traits occur much more frequently among the first degree relatives of schizophrenic patients than they do in the general population. These traits are far more common among the first degree relatives of schizophrenic patients than is schizophrenic psychosis. These traits are not clinically harmful, but they are useful scientifically, both as probes into the pathophysiology of schizophrenia, and as supplementary phenotypes in linkage analysis. There are three objectives of this proposal. The first is to map these traits in families of schizophrenic patients so that their distribution can be reliably ascertained. The second is to probe into the pathophysiology of two of these traits, eye tracking dysfunction (ETD) and spatial working memory (SWM) impairments. The third is to discover new such traits and to use them to increase our understanding of the pathophysiology and genetics of schizophrenia. ETD and SWM are examples of traits that aggregate in the first degree relatives of schizophrenic patients. Since they are frequently found in the relatives who do not express any schizophrenia like pathology, they cannot be secondary effects of schizophrenia, but are related in an unknown way to the biological processes underlying the disease. Both ETD and SWM impairments will be investigated using methods of cognitive psychology, psychophysics, and psychophysiology. For ETD parametric studies of motion perception will be complemented by fMRI studies. We will also investigate the integrity of object and semantic working memory along with SWM. The search for genetic markers linked to schizophrenia has been hindered by the low rate at which the illness recurs among family members of schizophrenic patients. Since these co-segregating traits are much more common among family members, they are useful as genetic indicators.The sample is drawn from McLean Hospital, and investigators from the wider Harvard community are centrally involved, including the Vision Sciences Lab, the Cognitive Sciences Lab, both in the Department of Psychology, and the MGH for fMRI.
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