Hippocampal Plasticity in Response to Exercise in Schizophrenia
Open accessAbstract
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.
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Three months of aerobic exercise training increases hippocampal volume in healthy individuals and in patients with schizophrenia by 12% and 16%, respectively.
“It has been shown that three months of aerobic exercise training increases hippocampal volume in healthy individuals and in patients with schizophrenia by 12% and 16%, respectively [235].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [235]
The claim reverses the percentages. The Abstract and “CHANGE IN HIPPOCAMPAL VOLUME AND EXERCISE” section report a 12% increase in patients with schizophrenia and a 16% increase in healthy controls after three months of aerobic exercise. (LLM, conf=0.95)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn people with schizophrenia, potential positive effects on mental health and cognitive symptoms have been suggested to be related to increases in hippocampal volume, but these findings in mental disorders have not been replicated in a recent meta-analysis of RCTs.
“Among people with schizophrenia, the potential positive effects on mental health and cognitive symptoms have been suggested to be related to increases in hippocampal volume [87], yet these findings in mental disorders have not been replicated in a recent meta-analysis of RCTs [8].”
From Exercise as Medicine for Mental and Substance Use Disorders: A Meta-review of the Benefits for Neuropsychiatric and Cognitive Outcomes (2020) · cites this paper as [87]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAerobic training can increase hippocampal volume in schizophrenic and healthy subjects.
“and can be increased by aerobic training of both schizophrenic and healthy subjects' (397).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [397]
Aerobic exercise interventions have been shown to increase hippocampal volume in patients with schizophrenia.
“AE interventions have also been shown to increase hippocampal volume in patients with mild cognitive impairments (ten Brinke et al., 2015), schizophrenia (Pajonk et al., 2010), and multiple sclerosis (Leavitt et al., 2014).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Pajonk et al., 2010
Growth in hippocampal volume and, in some cases, improvements in working memory performance are correlated with higher concentrations of NAA.
“N-acetylaspartate (NAA) is a metabolite indicative of neuronal integrity and a number of AE studies have demonstrated that the growth in hippocampal volume (Pajonk et al., 2010; Erickson et al., 2012; Gonzales et al., 2013; Wagner et al., 2015) and in some cases, improvements in working memory performance (Erickson et al., 2011) are both correlated with higher concentrations of NAA.”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Pajonk et al., 2010
In patients with schizophrenia, a 12-week AE intervention has led to increased hippocampal volume, hippocampal NAA concentration, and improved performances on short-term memory and working memory tasks.
“For example, in patients with schizophrenia a 12-week AE intervention has led to increased hippocampal volume, hippocampal NAA concentration and improved performances on short-term memory and working memory tasks (Pajonk et al., 2010; Lin et al., 2015; McEwen et al., 2015).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Pajonk et al., 2010
Both cross-sectional and interventional studies have demonstrated that AE can promote cognitive functioning in patients with schizophrenia across a range of cognitive domains including speed of processing, short-term and working memory, and visual learning.
“Both cross-sectional (Kimhy et al., 2014) and interventional studies (Pajonk et al., 2010; Oertel-Knöchel et al., 2014; Kimhy et al., 2015; McEwen et al., 2015) have demonstrated that AE can promote cognitive functioning in patients with schizophrenia across a range of cognitive domains including speed of processing, short-term and working memory and visual learning.”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Pajonk et al., 2010
Increases in cortical and hippocampal volume were found after periods of exercise in healthy individuals.
“Increases in the volume of the cortex 14-16,18 and hippocampus 17,19 were found after periods of exercise in healthy individuals.”
From Physical exercise keeps the brain connected: biking increases white matter integrity in patients with schizophrenia and healthy controls. (2015) · cites this paper as [19]
Physical exercise affects gray matter structure.
“Physical exercise has been reported to affect gray matter structure. 14-19”
From Physical exercise keeps the brain connected: biking increases white matter integrity in patients with schizophrenia and healthy controls. (2015) · cites this paper as [19]
In patients with schizophrenia, one study found hippocampal volume increase after exercise training, but other studies did not find increases in hippocampal volume or cortical density.
“In patients with schizophrenia, a period of exercise training resulted in hippocampal volume increase in one study 19 but other studies did not reveal increases in hippocampal volume 20 or cortical density. 18”
From Physical exercise keeps the brain connected: biking increases white matter integrity in patients with schizophrenia and healthy controls. (2015) · cites this paper as [19]
Few studies have evaluated the effect of lifestyle interventions on cardiorespiratory fitness in patients with schizophrenia, but they reported promising findings.
“For our key secondary outcome, cardiorespiratory fitness, few studies have evaluated the effect of lifestyle interventions in patients with schizophrenia, but they reported promising findings [43][44][45] .”
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- Authors
- Pajonk, F.-G., Wobrock, T., Gruber, O., Scherk, H., Berner, D., Kaizl, I., Kierer, A., Müller, S., Oest, M., Meyer, T., Backens, M., Schneider-Axmann, T., Thornton, A. E., Honer, W. G., & Falkai, P.
- Affiliations
- Universitätsklinikum des Saarlandes (DE)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-02-01
- Volume
- 67
- Issue
- 2
- Pages
- 133
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2161851141
- Cited by
- 592
- References
- 49
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 19 · 2023: 25 · 2022: 29 · 2021: 27 · 2020: 52 · 2019: 36 · 2018: 47 · 2017: 44 · 2016: 46 · 2015: 69 · 2014: 38 · 2013: 46 · 2012: 35
- FWCI
- 27.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Michael Smith Health Research BC
- Servier
- H. Lundbeck A/S
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- schizophrenia, hippocampal volume, hippocampal plasticity, aerobic exercise training, cycling, cardiorespiratory fitness, N-acetylaspartate, short-term memory, exercise intervention
- MeSH terms
- Adult, Aspartic Acid, Chronic Disease, Cognition Disorders, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Neuronal Plasticity, Neuropsychological Tests, Magnetic Resonance Spectroscopy, Schizophrenia, Exercise
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