Improving Cognition Through Telehealth Aerobic Exercise and Cognitive Training After a First Schizophrenia Episode

ABSTRACT This R01 confirmatory efficacy clinical trial application involves telehealth delivery of a treatment approach to improving core cognitive deficits in schizophrenia, using an experimental therapeutic design that NIMH has advocated. Our telehealth intervention approach combines neurotrophin-releasing aerobic exercise training with neuroplasticity-based cognitive training to enhance the impact of cognitive training on cognition. Telehealth cognitive training and telehealth physical exercise training address the NIMH strategic research priorities for creating innovative interventions that can be “disseminated broadly” and “readily taught to the existing workforce with minimal cost.” Cognitive training and physical exercise have each been shown separately to improve cognitive deficits in schizophrenia to some degree, and our previous research has shown that when combined they show promise of improving cognition and work/school functioning more than either treatment alone. In our preliminary studies, comparing the combined treatment with cognitive training without aerobic exercise, we find evidence of brain-derived neurotrophic factor (BDNF) target engagement, differential improvement in cognition, and prediction of later cognitive outcome from initial BDNF gain. The portability of the proposed intervention outside of academic research programs will be demonstrated by providing the interventions via videoconferencing. The proposed study will incorporate additional methods, such as Fitbit wrist-worn fitness trackers, web-based motivational support, and personalized text messages to encourage motivation and to maximize participation in the exercise condition. We will use Mature BDNF as our primary target and cognition as our primary outcome. We hypothesize that the increases in Mature BDNF associated with regular aerobic exercise provide a platform which allows neuroplasticity-based cognitive training to enhance cognition more quickly than is typically observed in studies of cognitive training alone. We hypothesize that combining aerobic exercise with cognitive training will produce larger cognitive improvements, relative to cognitive training without exercise, with all interventions conducted remotely via videoconferencing. Further, we hypothesize that a greater proportion of exercise sessions completed will be associated with greater cognitive improvement. The research will also test whether intrinsic motivation at baseline and increases in intrinsic motivation over time predict the extent of participation in the telehealth physical exercise program. Cognitive deficits in persons with schizophrenia are a major influence on their everyday functioning in the community. We target the period shortly after a first episode of schizophrenia to maximize the generalization of cognitive improvement to real-world functional outcome, before chronic disability is established. This telehealth cognitive training plus aerobic exercise clinical trial has the potential to test a hypothesized mechanism of action and to make a meaningful difference in the lives of individuals with severe mental illness.