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Cortico-striatal Function in Individuals at Genetic Risk for Schizophrenia


Evidence demonstrates that individuals with schizophrenia have impaired corticostriatal functioning. Non-psychotic relatives of patients with schizophrenia exhibit a subset of the deficits present in schizophrenia patients, suggesting that there are cognitive endophenotypes of this disorder and that these deficits appear to be associated with genetic liability for schizophrenia. In order to determine if a deficit in corticostriatal functioning is an endophenotype for schizophrenia, it is important to investigate the idea that genetic risk for schizophrenia is associated with impairment in striatal dependent tasks. Therefore, we will use both behavioral measures and fMRI to assess differences in performance level and pattern of brain activation associated with different striatal-dependent tasks to investigate the corticostriatal function of relatives of patients with schizophrenia. Both behavioral and fMRI studies will be conducted in healthy adolescent and adult relatives schizophrenic individuals and controls using cognitive and motor skill learning tasks. The behavioral studies will measure performance and function of two different corticostriatal loops and will investigate the developmental course for the behavior pattern of relatives of schizophrenia patients. The fMRI studies will expand the results of the behavioral studies and determine whether there is a difference in the pattern of brain activation between the adolescent relatives, adolescent controls, adult relatives, and adult controls. This research makes a novel contribution in that it demonstrates that individuals with genetic liability for schizophrenia exhibit deficits in corticostriatal function. Because these individuals do not have the disease, their performance gives insights into whether corticostriatal function is an endophonotype of schizophrenia, independent of the effects of medication and the illness itself and also leads to an increased understanding of the neural mechanisms of schizophrenia and advances the search for the treatment of this severe disorder.

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