Remediation of Working Memory in Schizophrenia

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Schizophrenia is among the most disabling illnesses of adults in the world. With illness onset typically occurring in young adulthood, individuals with schizophrenia often struggle to establish and maintain social and work roles in the community. In recognition of the profound disability associated with schizophrenia, the Veteran's Health Administration has prioritized provision of mental health care services to adults with severe and persistent mental illnesses. The President's New Freedom Commission called for the development of mental health care services that focus on "increasing consumer's ability to successfully cope with life challenges, on facilitating recovery, and on building resilience." The proposed intervention study is designed to enhance cognition and psychosocial functioning in patients. The cognitive dysfunction associated with schizophrenia has been found to be one of the strongest predictors of how well patients do in the community. Cognitive remediation is a computer-based intervention that was developed to restore cognitive functioning in patients with brain injury. This intervention has been adapted successfully for use with patients with schizophrenia. The proposed treatment study draws upon recent research findings which suggest both that working memory is a critical, potentially performance-limiting, cognitive deficit in schizophrenia and that with intervention, clinically significant change can occur within this domain. The primary aim of the proposed study is to test the efficacy of a novel cognitive remediation intervention that targets working memory-related functions. To accomplish this goal, 80 volunteer patients with schizophrenia will be enrolled and randomized to either a cognitive remediation condition that targets working memory or a computer skills training intervention that teaches computer applications. In both conditions participants will receive computer training three times a week for 4 months. We hypothesize that patients who receive the cognitive remediation intervention will demonstrate significantly greater change on neuropsychological measures of working memory and executive abilities than patients who receive the computer skills course. In addition, we hypothesize that the intervention- induced cognitive change will be associated with concurrent improvements in functional capacity and psychosocial functioning in the community. A second study goal is to examine the stability of the intervention- induced changes in cognition. Cognition and psychosocial functioning will be reassessed 4 and 8 months after treatment termination to examine the stability of treatment effects and to assess whether a less intense maintenance training (once a week sessions) provides any additional benefit to participants. Lastly, this study will examine in an exploratory manner whether there are individual differences in treatment response. The Val158Met polymorphism of the COMT gene has been found to be associated with working memory and prefrontal dysfunction in schizophrenia. The proposed study will test whether the COMT polymorphism is predictive of response to cognitive remediation.