This R34 application is designed to move our innovative treatment approach to improving cognition in schizophrenia from the feasibility stage to the pilot intervention trial stage. We propose a randomized controlled 6-month trial of the efficacy of a novel intervention combining neuroplasticity-based cognitive training with neurotrophin-releasing aerobic exercise, compared to the same cognitive training alone. Both of these treatments address the NIMH Strategic Plan and NIMH Director Tom Insel's request to create innovative interventions that can be """"""""disseminated broadly"""""""" and """"""""readily taught to the existing workforce with minimal cost."""""""" The primary treatment targets are overall cognitive deficit level and impairment in independent living skills. A secondary outcome variable will be a key neurotrophic growth factor, brain-derived neurotrophic factor (BDNF). We hypothesize that combining neuroplasticity-based computerized cognitive training and neurotrophin-enhancing physical exercise will produce large cognitive and functional improvements, even relative to cognitive training alone. Based on theoretical considerations and our initial pilot data, the new cognitive training plus aerobic exercise intervention has the potential to make a real difference in the lives of individuals with severe mental illness. Adding aerobic exercise to our cognitive training program will have the additional benefit of helping to ameliorate medication side effects, reduce the risk for developing metabolic syndrome, and help to prevent the deterioration in physical health that usually follows the onset of schizophrenia and its pharmacologic treatment. Cognitive deficits in persons with schizophrenia present an enormous challenge when helping them to return to functioning in the community. Cognitive remediation and physical exercise have each been shown separately to have promise for improving cognitive deficits in schizophrenia, but used separately yield moderate effects. Our initial pilot data suggest that integrating these two interventions produces larger cognitive gains than the cognitive training alone. We posit that the increases in neurotrophic factors associated with regular aerobic exercise provide a platform which allows neuroplasticity-based cognitive training to impact cognition to a greater degree than is typically observed in studies of cognitive training alone. We target the period shortly after a first episode of schizophrenia to maximize the generalization of cognitive improvement to functional outcome, before chronic disability is established.

Public Health Relevance

This proposal focuses on a small randomized controlled trial that will serve as a pilot intervention study of a new treatment for cognitive deficits in schizophrenia. The new treatment involves using aerobic exercise to boost neurotropins and enhance the impact of systematic cognitive training, thereby remediating a larger portion of the cognitive impairment in this disorder. Successful remediation of the core cognitive deficits shortly after a first episode of schizophrenia is likely to result in much more effective generalization to improved functional outcome than intervention later, after disability is well established, and would have major public health significance for community functioning and potentially also for physical health of individuals with schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Planning Grant (R34)
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Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Morris, Sarah E
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Nuechterlein, Keith H (2017) The Pioneering Contributions of Irving Gottesman: An Appreciation. Clin Psychol Sci 5:424-426
Nuechterlein, Keith H; Ventura, Joseph; McEwen, Sarah C et al. (2016) Enhancing Cognitive Training Through Aerobic Exercise After a First Schizophrenia Episode: Theoretical Conception and Pilot Study. Schizophr Bull 42 Suppl 1:S44-52
McEwen, Sarah C; Hardy, Anthony; Ellingson, Benjamin M et al. (2015) Prefrontal and Hippocampal Brain Volume Deficits: Role of Low Physical Activity on Brain Plasticity in First-Episode Schizophrenia Patients. J Int Neuropsychol Soc 21:868-79