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Abstract

Treatment-resistant schizophrenia is characterized by deficits in cognition, emotion recognition, cardiovascular health, and brain white matter (WM). Reductions in frontal-temporal white matter (WM) volumes in schizophrenia are associated with psychotic symptoms, cognitive deficits, poor emotional recognition, and cardiometabolic disorder. Regular exercise is posited to attenuate or restore functionality in multiple domains, but the efficacy of exercise as a non-pharmacological treatment for schizophrenia is unknown. Our goal was to examine the effects of exercise on WM in treatment-resistant schizophrenia. Fifteen treatment-resistant schizophrenia patients and 10 age, gender and education matched healthy volunteers were included in a 12-week exercise intervention. At baseline, compared to healthy volunteers, patients had decreased myelin water fraction (MWF) in the genu, callosal body, splenium, external capsule, cingulum, superior longitudinal fasciculus, and forceps minor with corrected p-values ranging from 0.03 to 0.04 and hedges’ g effect sizes ranging from -0.76 to -1.03. Patients also had decreased fractional anisotropy (FA) in the genu (p = 0.03, g = -1.29) and the forceps minor (p = 0.03, g = -1.23). Patients also had slower reaction times in emotion expression tasks (p < 0.01, g = 1.30), slower domain level speed of processing (p < 0.01, g = -1.91), and lower working memory (p