BACKGROUND: Schizophrenia (SCZ) is a severe, chronic illness characterized by psychotic symptoms and impairments in many cognitive domains. Dysregulation of brain derived neurotrophic factor (BDNF) is associated with the cognitive impairments seen in patients with SCZ. Given the growing literature supporting a positive effect of aerobic exercise on cognition in other populations, we hypothesized that a structured aerobic exercise program would improve cognitive and functional outcomes in subjects with SCZ, potentially mediated by increases in BDNF. METHOD(S): The study was a small randomized parallel group clinical trial of subjects with SCZ comparing 12 weeks of aerobic exercise (AE) against control (CON) stretching and balance training. At baseline, week 12, and week 20 we collected serum samples for analysis of brain derived neurotrophic factor (BDNF), and assessed functional, physical, and cognitive outcomes. Linear regression models were used to compare change scores between timepoints. RESULT(S): We randomized 21 subjects to AE and 17 to CON; however, only 9 AE and 6 CON completed their programs. Subjects in both groups were slower at the 400 m walk in week 12 compared to baseline, but the AE group had significantly less slowing than the CON group (B = -28.32, p = 0.011). Between week 12 and week 20, the AE group had a significantly greater change score on the Composite and Visual Learning Domain of the MATRICS Consensus Cognitive Battery (B = 5.11, p = 0.03; B = 13.96, p = 0.006). CONCLUSION(S): These results indicate that participation in a structured aerobic exercise paradigm may modestly blunt physical function decline and enhance cognitive function in individuals with SCZ.

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