Hippocampal plasticity in response to exercise in schizophrenia

Arch Gen Psychiatry. 2010 Feb;67(2):133-43. doi: 10.1001/archgenpsychiatry.2009.193.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Chronic Disease
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology
  • Exercise*
  • Hippocampus / anatomy & histology*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Neuronal Plasticity / physiology*
  • Neuropsychological Tests
  • Schizophrenia / epidemiology
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology*


  • Aspartic Acid
  • N-acetylaspartate