Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls.

Scheewe, Thomas W.; van Haren, Neeltje E.M.; Sarkisyan, Gayane; Schnack, Hugo G.; Brouwer, Rachel M.; de Glint, Maria; Hulshoff Pol, Hilleke E.; Backx, Frank J.G.; Kahn, René S.; Cahn, Wiepke

doi:10.1016/j.euroneuro.2012.08.008

Cited by 148Schizophrenia research and treatmentPhysical Activity and HealthDementia and Cognitive Impairment Research

Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls.

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Scheewe, Thomas W., van Haren, Neeltje E.M., Sarkisyan, Gayane, Schnack, Hugo G., Brouwer, Rachel M., de Glint, Maria, Hulshoff Pol, Hilleke E., Backx, Frank J.G. +2 more·2013·European Neuropsychopharmacology

DOI 10.1016/j.euroneuro.2012.08.008

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Abstract

The objective of this study was to examine exercise effects on global brain volume, hippocampal volume, and cortical thickness in schizophrenia patients and healthy controls. Irrespective of diagnosis and intervention, associations between brain changes and cardiorespiratory fitness improvement were examined. Sixty-three schizophrenia patients and fifty-five healthy controls participated in this randomised controlled trial. Global brain volumes, hippocampal volume, and cortical thickness were estimated from 3-Tesla MRI scans. Cardiorespiratory fitness was assessed with a cardiopulmonary ergometer test. Subjects were assigned exercise therapy or occupational therapy (patients) and exercise therapy or life-as-usual (healthy controls) for six months 2h weekly. Exercise therapy effects were analysed for subjects who were compliant at least 50% of sessions offered. Significantly smaller baseline cerebral (grey) matter, and larger third ventricle volumes, and thinner cortex in most areas of the brain were found in patients versus controls. Exercise therapy did not affect global brain and hippocampal volume or cortical thickness in patients and controls. Cardiorespiratory fitness improvement was related to increased cerebral matter volume and lateral and third ventricle volume decrease in patients and to thickening in the left hemisphere in large areas of the frontal, temporal and cingulate cortex irrespective of diagnosis. One to 2h of exercise therapy did not elicit significant brain volume changes in patients or controls. However, cardiorespiratory fitness improvement attenuated brain volume changes in schizophrenia patients and increased thickness in large areas of the left cortex in both schizophrenia patients and healthy controls.

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Some randomized controlled trials have found that aerobic exercise did not have an impact on hippocampal volume.
“While some RCTs have found that AE did not have an impact on hippocampal volume (Ruscheweyh et al., 2011; Scheewe et al., 2013; Krogh et al., 2014; Rosenbaum et al., 2015; Malchow et al., 2016), it is possible that such discrepancies are caused by a lack of consistency in AE protocols used (Prakash et al., 2015) or in the methods of calculating hippocampal volume (Niemann 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 Scheewe et al., 2013
Other studies have found AE interventions to have no impact on hippocampal volume or function in patients with schizophrenia.
“However, other studies have found AE interventions to of had no impact on hippocampal volume or function in patients with schizophrenia (Scheewe et al., 2013; Rosenbaum 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 Scheewe et al., 2013
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 [20]
Some studies did not find significant effects of exercise on cortical architecture.
“However, others did not find significant effect, eg, on cortical architecture. 20-22”
From Physical exercise keeps the brain connected: biking increases white matter integrity in patients with schizophrenia and healthy controls. (2015) · cites this paper as [20]

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Kandola, A., Hendrikse, J., Lucassen, P. J., & Yücel, M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00373 · Cited by 155 · see citing works
“Although data was not available for all studies (Rosenbaum et al., 2015) attendance rates for AE sessions were generally higher in those studies that did ﬁnd improvements in hippocampal volume and function (Pajonk et al., 2010; Lin et al., 2015) than those which did not (Scheewe et al., 2013).”
Influential
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Polygenic risk has an impact on the structural plasticity of hippocampal subfields during aerobic exercise combined with cognitive remediation in multi-episode schizophrenia
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Bipolar and psychotic disorders in elite athletes: a narrative review
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POSITIVE IMPACT OF PRESCRIBED PHYSICAL ACTIVITY ON SYMPTOMS OF SCHIZOPHRENIA: RANDOMIZED CLINICAL TRIAL
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Effects of Exercise on Physical and Mental Health, and Cognitive and Brain Functions in Schizophrenia: Clinical and Experimental Evidence
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A Critical Systematic Review of Current Evidence on the Effects of Physical Exercise on Whole/Regional Grey Matter Brain Volume in Populations at Risk of Neurodegeneration
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Aerobic Exercise in People with Schizophrenia: Neural and Neurocognitive Benefits
Vakhrusheva, J., Marino, B., Stroup, T. S., & Kimhy, D. (2016) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-016-0077-2 · Cited by 50 · see citing works
Understanding the Neurophysiological and Molecular Mechanisms of Exercise-Induced Neuroplasticity in Cortical and Descending Motor Pathways: Where Do We Stand?
Nicolini, C., Fahnestock, M. L., Gibala, M. J., & Nelson, A. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.12.013 · Cited by 50 · see citing works
Multi-Level Meta-Analysis of Physical Activity Interventions During Childhood: Effects of Physical Activity on Cognition and Academic Achievement
Vasilopoulos, F., Jeffrey, H., Wu, Y., & Dumontheil, I. (2023) · Educational Psychology Review · doi:10.1007/s10648-023-09760-2 · Cited by 56 · see citing works
Effects of childhood and adolescence physical activity patterns on psychosis risk—a general population cohort study
Sormunen, E., Saarinen, M. M., Salokangas, R. K. R., Telama, R., Hutri‐Kähönen, N., Tammelin, T., Viikari, J. S. A., Raitakari, O. T., & Hietala, J. A. (2017) · Schizophrenia · doi:10.1038/s41537-016-0007-z · Cited by 48 · see citing works
The effects of aerobic exercise on cognition in schizophrenia: A 3-month follow-up study
Su, C., Wang, P., Lin, Y.-J., Tang, T., Liu, M., & Chen, M. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.08.011 · Cited by 46 · see citing works
A 16-Week Aerobic Exercise Intervention Does Not Affect Hippocampal Volume and Cortical Thickness in Mild to Moderate Alzheimer’s Disease
Frederiksen, K. S., Larsen, C. T., Hasselbalch, S. G., Christensen, A. N., Høgh, P., Wermuth, L., Andersen, B. B., Siebner, H. R., & Garde, E. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00293 · Cited by 46 · see citing works
Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study
Caspi, Y., Brouwer, R. M., Schnack, H. G., van de Nieuwenhuijzen, M. E., Cahn, W., Kahn, R. S., Niessen, W. J., van der Lugt, A., & Pol, H. E. H. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116842 · Cited by 47 · see citing works
Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence
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Interventions for social and community participation for adults with intellectual disability, psychosocial disability or on the autism spectrum: An umbrella systematic review
Giummarra, M. J., Randjelovic, I., & O’Brien, L. (2022) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2022.935473 · Cited by 42 · see citing works
Association between actigraphy-derived physical activity and cognitive performance in patients with schizophrenia
Chen, L., Steptoe, A., Chung, M.-S., & Ku, P. (2016) · Psychological Medicine · doi:10.1017/s0033291716000921 · Cited by 41 · see citing works
Neural correlates of exercise training in individuals with schizophrenia and in healthy individuals: A systematic review
van der Stouwe, E. C. D., van Busschbach, J. T., de Vries, B., Cahn, W., Aleman, A., & Pijnenborg, G. H. M. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.04.018 · Cited by 40 · see citing works
Combined effects of physical exercise and education on age-related cortical thinning in cognitively normal individuals
Lee, J. S., Shin, H. Y., Kim, Y. J., Jang, Y. K., Jung, N., Lee, J., Kim, Y. J., Chun, P., Yang, J., Lee, J., et al. (2016) · Scientific Reports · doi:10.1038/srep24284 · Cited by 39 · see citing works
Causal effects of air pollution on mental health among Adults——An exploration of susceptible populations and the role of physical activity based on a longitudinal nationwide cohort in China
Ju, K., Lu, L., Wang, W., Chen, T., Yang, C., Zhang, E., Xu, Z., Li, S., Song, J., Pan, J., et al. (2022) · Environmental Research · doi:10.1016/j.envres.2022.114761 · Cited by 42 · see citing works
Can Exercise Increase Fitness and Reduce Weight in Patients with Schizophrenia and Depression?
Krogh, J., Speyer, H., Nørgaard, H. C. B., Moltke, A., & Nordentoft, M. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00089 · Cited by 34 · see citing works
What are the top 10 physical activity research questions in schizophrenia?
Vancampfort, D., Rosenbaum, S., Probst, M., Connaughton, J., du Plessis, C., Yamamoto, T., & Stubbs, B. (2016) · Disability and Rehabilitation · doi:10.3109/09638288.2015.1116622 · Cited by 34 · see citing works
Effect of aerobic exercise combined with cognitive remediation on cortical thickness and prediction of social adaptation in patients with schizophrenia
Takahashi, S., Keeser, D., Rauchmann, B., Schneider-Axmann, T., Keller-Varady, K., Maurus, I., Dechent, P., Wobrock, T., Hasan, A., Schmitt, A., et al. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.11.004 · Cited by 34 · see citing works
Aerobic exercise in severe mental illness: requirements from the perspective of sports medicine
Falkai, P., Schmitt, A., Rosenbeiger, C. P., Maurus, I., Hattenkofer, L., Hasan, A., Malchow, B., Heim-Ohmayer, P., Halle, M., & Heitkamp, M. (2021) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-021-01360-x · Cited by 34 · see citing works
Higher VO2max is associated with thicker cortex and lower grey matter blood flow in older adults
Olivo, G., Nilsson, J., Garzón, B., Lebedev, A. V., Wåhlin, A., Tarassova, O., Ekblom, M., & Lövdén, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-96138-5 · Cited by 33 · see citing works
Exercise Induced Neuroplasticity to Enhance Therapeutic Outcomes of Cognitive Remediation in Schizophrenia: Analyzing the Role of Brai nderived Neurotrophic Factor
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Aerobic exercise intervention in young people with schizophrenia spectrum disorders; improved fitness with no change in hippocampal volume.
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A Pilot Study Describing Physical Activity in Persons with Schizophrenia Spectrum Disorders (SSDS) after an Exercise Program
Beebe, L. H., Smith, K., Roman, M. W., Burk, R., McIntyre, K., Dessieux, O. L., Tavakoli, A. S., & Tennison, C. (2013) · Issues in Mental Health Nursing · doi:10.3109/01612840.2012.746411 · Cited by 32 · see citing works
Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients
Papiol, S., Keeser, D., Hasan, A., Schneider-Axmann, T., Raabe, F. J., Degenhardt, F., Rossner, M. J., Bickeböller, H., Cantuti‐Castelvetri, L., Simons, M., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0618-z · Cited by 32 · see citing works
DAily time use, Physical Activity, quality of care and interpersonal relationships in patients with Schizophrenia spectrum disorders (DiAPASon): an Italian multicentre study
de Girolamo, G., Rocchetti, M., Benzi, I. M. A., Agosta, S., Casiraghi, L., Ferrari, C., Franceschi, N. D., Macis, A., Pogliaghi, S., & Starace, F. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02588-y · Cited by 32 · see citing works
Functional brain networks in the schizophrenia spectrum and bipolar disorder with psychosis
van Dellen, E., Börner, C., Schutte, M. J. L., van Montfort, S. J. T., Abramovic, L., Boks, M. P., Cahn, W., van Haren, N. E. M., Mandl, R. C. W., Stam, C. J., et al. (2020) · Schizophrenia · doi:10.1038/s41537-020-00111-6 · Cited by 32 · see citing works
Effect of 5 Years of Exercise Intervention at Different Intensities on Brain Structure in Older Adults from the General Population: A Generation 100 Substudy
Pani, J., Reitlo, L. S., Evensmoen, H. R., Lydersen, S., Wisløff, U., Stensvold, D., & Haberg, A. K. (2021) · Clinical Interventions in Aging · doi:10.2147/cia.s318679 · Cited by 32 · see citing works
Prefrontal and hippocampal brain volume deficits: role of low physical activity on brain plasticity in first-episode schizophrenia patients.
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Endurance training in patients with schizophrenia and healthy controls: differences and similarities
Keller-Varady, K., Hasan, A., Schneider-Axmann, T., Hillmer-Vogel, U., Adomßent, B., Wobrock, T., Schmitt, A., Niklas, A., Falkai, P., & Malchow, B. (2015) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-015-0651-8 · Cited by 29 · see citing works
A systematic review of trials investigating strength training in schizophrenia spectrum disorders
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Effects of chronic exercise and treatment with the antipsychotic drug olanzapine on hippocampal volume in adult female rats.
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Designing a feasible exercise intervention in first-episode psychosis: Exercise quality, engagement and effect
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Systematic Review and Meta-analysis of Exercise Interventions for Psychotic Disorders: The Impact of Exercise Intensity, Mindfulness Components, and Other Moderators on Symptoms, Functioning, and Cardiometabolic Health
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Cross-sectional associations between cortical thickness and physical activity in older adults with spontaneous memory complaints: The MAPT Study
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Efficacy and feasibility of aerobic exercise interventions as an adjunctive treatment for patients with schizophrenia: a meta-Analysis
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Combined aerobic and resistance exercise interventions for individuals with schizophrenia: A systematic review
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Why Do People With Schizophrenia Exercise? A Mixed Methods Analysis Among Community Dwelling Regular Exercisers
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White matter microstructure and volitional motor activity in schizophrenia: A diffusion kurtosis imaging study
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The synergistic benefits of physical and cognitive exercise in schizophrenia: Promoting motivation to enhance community effectiveness
Choi, J., Taylor, B. A., Fiszdon, J. M., Kurtz, M. M., Tek, C., Dewberry, M. J., Haber, L. C., Shagan, D. S., Assaf, M., & Pearlson, G. D. (2019) · Schizophrenia Research Cognition · doi:10.1016/j.scog.2019.100147 · Cited by 21 · see citing works
Protocol for CHANGE: a randomized clinical trial assessing lifestyle coaching plus care coordination versus care coordination alone versus treatment as usual to reduce risks of cardiovascular disease in adults with schizophrenia and abdominal obesity
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Evaluation of the benefits of exercise on cognition in major depressive disorder
Greer, T. L., Furman, J. L., & Trivedi, M. H. (2017) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2017.06.002 · Cited by 20 · see citing works
Physical exercise keeps the brain connected by increasing white matter integrity in healthy controls
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Physical Activity, Positive and Negative Symptoms of Psychosis, and General Psychopathology among People with Psychotic Disorders: A Meta-Analysis
Swora, E., Boberska, M., Kuliś, E., Knoll, N., Keller, J., & Łuszczyńska, A. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11102719 · Cited by 19 · see citing works
Exercise prevents downregulation of hippocampal presynaptic proteins following olanzapine-elicited metabolic dysregulation in rats: distinct roles of inhibitory and excitatory terminals.
Ramos-Miguel, A., Honer, W. G., Boyda, H. N., Sawada, K., Beasley, C. L., Procyshyn, R. M., & Barr, A. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.06.022 · Cited by 18 · see citing works
A combined exercise and cognitive training intervention induces fronto-cingulate cortical plasticity in first-episode psychosis patients
McEwen, S. C., Jarrahi, B., Ventura, J., Subotnik, K. L., Nguyen, J., Woo, S. M., & Nuechterlein, K. H. (2022) · Schizophrenia Research · doi:10.1016/j.schres.2022.12.001 · Cited by 18 · see citing works
Computerized physical activity training for persons with severe mental illness - experiences from a communal supported housing project
Gyllensten, A., & Forsberg, K. (2017) · Disability and Rehabilitation: Assistive Technology · doi:10.1080/17483107.2016.1263881 · Cited by 14 · see citing works
Chronotropic incompetence of the heart is associated with exercise intolerance in patients with schizophrenia
Herbsleb, M., Schumann, A., Malchow, B., Puta, C., Schulze, P. C., Gabriel, H. W., & Bär, K. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.02.020 · Cited by 17 · see citing works
Longitudinal study of the effect of a 5-year exercise intervention on structural brain complexity in older adults. A Generation 100 substudy
Pani, J., Marzi, C., Stensvold, D., Wisløff, U., Haberg, A. K., & Diciotti, S. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.119226 · Cited by 16 · see citing works
Clinical and neuroimaging correlates of cardiorespiratory fitness in adolescents with bipolar disorder
Popel, N., Kennedy, K. G., Fıksenbaum, L., Mitchell, R. H. B., MacIntosh, B. J., & Goldstein, B. I. (2020) · Bipolar Disorders · doi:10.1111/bdi.12993 · Cited by 16 · see citing works
Physical and mental health in adolescence: novel insights from a transdiagnostic examination of FitBit data in the ABCD study
Damme, K. S. F., Vargas, T., Walther, S., Shankman, S. A., & Mittal, V. A. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02794-2 · Cited by 19 · see citing works
Longitudinal Effects of Physical Activity Change on Hippocampal Volumes over up to 12 Years in Middle and Older Age Community-Dwelling Individuals
Fraser, M. A., Walsh, E., Shaw, M. E., Anstey, K. J., & Cherbuin, N. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab375 · Cited by 14 · see citing works
A web-based adapted physical activity program (e-APA) versus health education program (e-HE) in patients with schizophrenia and healthy volunteers: study protocol for a randomized controlled trial (PEPSY V@Si)
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Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia—Data From a Multicenter Randomized-Controlled Study
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Authors: Scheewe, T. W., van Haren, N. E. M., Sarkisyan, G., Schnack, H. G., Brouwer, R. M., de Glint, M., Hulshoff Pol, H. E., Backx, F. J. G., Kahn, R. S., & Cahn, W.
Affiliations: University Medical Center Utrecht (NL)
Corresponding author: Scheewe, Thomas W.
ORCID: Schnack, Hugo G.
Brouwer, Rachel M.
Backx, Frank J.G.
Kahn, René S.
Cahn, Wiepke
Venue: European Neuropsychopharmacology
Publisher: Elsevier BV
Published: 2013-07
Volume: 23
Issue: 7
Pages: 675-685
ISSN: 0924-977X (ISSN-L)
DOI: 10.1016/j.euroneuro.2012.08.008
OpenAlex: W2030455633
Cited by: 148
References: 65
Citations by year: 2026: 4 · 2025: 3 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 18 · 2019: 11 · 2018: 10 · 2017: 12 · 2016: 17 · 2015: 19 · 2014: 5 · 2013: 8
FWCI: 7.30
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 338 d)
Locations: European Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: GGZ Friesland
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Physiology › Physical Activity and Health
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: exercise therapy, cardiorespiratory fitness, schizophrenia, brain volume, hippocampal volume, cortical thickness, third ventricle, occupational therapy, brain structural changes
MeSH terms: Adolescent, Adult, Brain, Cerebral Cortex, Exercise Test, Exercise Therapy, Female, Hippocampus, Humans, Male, Middle Aged, Occupational Therapy, Physical Fitness, Psychiatric Status Rating Scales, Schizophrenia, Antipsychotic Agents, Case-Control Studies, Neuroimaging

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Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls.

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