Hippocampal Plasticity in Response to Exercise in Schizophrenia

Context: Hippocampal volume is lower than expected in patients with schizophrenia; however, whether this represents a fixed deficit is uncertain. Exercise is a stimulus to hippocampal plasticity. Objective: To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness. Design: Randomized controlled study. Setting: Patients attending a day hospital program or an outpatient clinic. Patients or Other Participants: Male patients with chronic schizophrenia and matched healthy subjects. Interventions: Aerobic exercise training (cycling) and playing table football (control group) for a period of 3 months. Main Outcome Measures: Magnetic resonance imaging of the hippocampus. Secondary outcome measures were magnetic resonance spectroscopy, neuropsychological (Rey Auditory Verbal Learning Test, Corsi block-tapping test), and clinical (Positive and Negative Syndrome Scale) features. Results: Following exercise training, relative hippocampal volume increased significantly in patients (12%) and healthy subjects (16%), with no change in the nonexercise group of patients (-1%). Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption (r=0.71; P=.003). In the schizophrenia exercise group (but not the controls), change in hippocampal volume was associated with a 35% increase in the N-acetylaspartate to creatine ratio in the hippocampus. Finally, improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume (r=0.51; P<.05). Conclusion: These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise.