The Impact of Aerobic Exercise on Brain-Derived Neurotrophic Factor and Neurocognition in Individuals With Schizophrenia: A Single-Blind, Randomized Clinical Trial

Abstract

Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits. Yet, findings from studies of animals, clinical and nonclinical populations have linked neurocognitive improvements to increases in aerobic fitness (AF) via aerobic exercise training (AE). Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor (BDNF). However, the impact of AE on neurocognition, and the putative role of BDNF, have not been investigated in schizophrenia. Employing a proof-of-concept, single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive standard psychiatric treatment (n = 17; "treatment as usual"; TAU) or attend a 12-week AE program (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed assessments of AF (indexed by VO2 peak ml/kg/min), neurocognition (MATRICS Consensus Cognitive Battery), and serum-BDNF before and after and 12-week period. Twenty-six participants (79%) completed the study. At follow-up, the AE participants improved their AF by 18.0% vs a -0.5% decline in the TAU group (P = .002) and improved their neurocognition by 15.1% vs -2.0% decline in the TAU group (P = .031). Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4% and 14.6% of the neurocognitive improvement variance, respectively. The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population. Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe, nonstigmatizing, and side-effect-free intervention.

Keywords: aerobic fitness; brain-derived neurotrophic factor/active-play video games; cognition; neurotrophins.

Fig. 1.

Comparison of changes in aerobic fitness and neurocognitive functioning following aerobic exercise training or treatment as usual. n = 26 (TAU = 13, AE = 13); Changes in aerobic fitness are indexed by VO₂ peak (ml/kg/min); Changes in neurocognition are indexed by MATRICS Consensus Cognitive Battery composite T-scores.

Fig. 2.

Distribution of changes in neurocognitive functioning following aerobic exercise training or treatment as usual. n = 26 (TAU = 13, AE = 13); Neurocognitive Functioning—MATRICS Consensus Cognitive Battery composite T-score.

Fig. 3.

Association of changes in aerobic fitness, serum BDNF, and neurocognition. n = 26 (AE = 13, TAU = 13). (A) Association of changes in aerobic fitness and changes in neurocognition. (B) Association of changes in serum-BDNF and changes in neurocognition.