The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]

Background Exercise for post-traumatic stress disorder (PTSD) is a potentially effective adjunct to psychotherapy. However, the biopsychosocial mechanisms of exercise are not well understood. This co-produced living systematic review synthesizes evidence from human and non-human studies. Methods We...

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Main Authors: David Gilbert, Thomy Tonia, Edoardo G. Ostinelli, Toshi A. Furukawa, Hossein Dehdarirad, Emily Sena, Fiona Ramage, Spyridon Siafis, Virginia Chiocchia, Claire Stansfield, Simonne Wright, Francesca Tinsdeall, Claire Friedrich, James Thomas, Charlotte Austin, Malcolm Macleod, Georgia Salanti, Jaycee Kennett, Soraya Seedat, Olufisayo Elugbadebo, Andrea Cipriani, Ouma Simple, Jennifer Potts
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Language:English
Published: Wellcome 2025-04-01
Series:Wellcome Open Research
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Online Access:https://wellcomeopenresearch.org/articles/9-720/v3
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author David Gilbert
Thomy Tonia
Edoardo G. Ostinelli
Toshi A. Furukawa
Hossein Dehdarirad
Emily Sena
Fiona Ramage
Spyridon Siafis
Virginia Chiocchia
Claire Stansfield
Simonne Wright
Francesca Tinsdeall
Claire Friedrich
James Thomas
Charlotte Austin
Malcolm Macleod
Georgia Salanti
Jaycee Kennett
Soraya Seedat
Olufisayo Elugbadebo
Andrea Cipriani
Ouma Simple
Jennifer Potts
author_facet David Gilbert
Thomy Tonia
Edoardo G. Ostinelli
Toshi A. Furukawa
Hossein Dehdarirad
Emily Sena
Fiona Ramage
Spyridon Siafis
Virginia Chiocchia
Claire Stansfield
Simonne Wright
Francesca Tinsdeall
Claire Friedrich
James Thomas
Charlotte Austin
Malcolm Macleod
Georgia Salanti
Jaycee Kennett
Soraya Seedat
Olufisayo Elugbadebo
Andrea Cipriani
Ouma Simple
Jennifer Potts
author_sort David Gilbert
collection DOAJ
description Background Exercise for post-traumatic stress disorder (PTSD) is a potentially effective adjunct to psychotherapy. However, the biopsychosocial mechanisms of exercise are not well understood. This co-produced living systematic review synthesizes evidence from human and non-human studies. Methods We Included controlled human and non-human studies involving searches of multiple electronic databases (until 31.10.23). Records were screened, extracted, assessed for risk of bias, and reconciled by two independent reviewers. The primary outcome for human studies was PTSD symptom severity, while outcomes of interest for non-human studies included freezing behaviour, fear memory, fear generalization, startle response, and locomotion. Data were synthesised with random-effects meta-analysis. Results Eleven human studies met the eligibility criteria. Overall, exercise was not associated with symptom severity improvement compared to control (standardized mean difference [SMD] -0.08, 95% confidence interval [CI] -0.24 to 0.07; 8 studies, one at low risk of bias). High-intensity exercise reduced PTSD symptoms scores more than moderate-intensity exercise. There was insufficient data to examine the effects of exercise on functional impairment, PTSD symptom clusters, and PTSD remission. Only three studies, all at high risk of bias, examined mechanisms of exercise with inconclusive results. Exercise was associated with improvement in all behavioural outcomes, including locomotor activity (SMD 1.30, 95% CI 0.74 to 1.87, 14 studies), and changes in several neurobiological markers, including increase in brain-derived neurotrophic factor (SMD 1.79, 95% CI 0.56 to 3.01). Conclusions While non-human studies provide compelling evidence for the beneficial effects of exercise, human trials do not. Evidence from non-human studies suggest that exercise might increase the levels of brain-derived neurotrophic factor, enhance cognitive appraisal, and improve perceived exertion. Overall, the paucity of data on the effectiveness of exercise in PTSD and mechanisms of action underscore the need for rigorous trials. Registration The protocol was registered with PROSPERO (ID:453615; 22.08.2023).
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spelling doaj-art-897dfdc10fa348e491e66d521cde6f532025-08-20T01:54:41ZengWellcomeWellcome Open Research2398-502X2025-04-01910.12688/wellcomeopenres.23033.326562The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]David Gilbert0Thomy Tonia1Edoardo G. Ostinelli2https://orcid.org/0000-0002-8717-0832Toshi A. Furukawa3Hossein Dehdarirad4Emily Sena5https://orcid.org/0000-0002-3282-8502Fiona Ramage6https://orcid.org/0000-0002-4855-7911Spyridon Siafis7https://orcid.org/0000-0001-8264-2039Virginia Chiocchia8https://orcid.org/0000-0002-6196-3308Claire Stansfield9Simonne Wright10https://orcid.org/0000-0003-3295-256XFrancesca Tinsdeall11https://orcid.org/0009-0008-9248-2954Claire Friedrich12https://orcid.org/0000-0002-5841-4324James Thomas13https://orcid.org/0000-0003-4805-4190Charlotte Austin14Malcolm Macleod15https://orcid.org/0000-0001-9187-9839Georgia Salanti16Jaycee Kennett17https://orcid.org/0000-0002-7312-8676Soraya Seedat18Olufisayo Elugbadebo19https://orcid.org/0000-0003-3221-1323Andrea Cipriani20Ouma Simple21https://orcid.org/0000-0002-4510-6736Jennifer Potts22GALENOS Global Experiential Advisory Board, InHealth Associates, London, UKUniversity of Bern Institute of Social and Preventive Medicine, Bern, SwitzerlandDepartment of Psychiatry, University of Oxford, Oxford, England, UKKyoto University Office of Institutional Advancement and Communications, Kyoto, JapanEPPI Centre, UCL Social Research Institute, University College London, London, England, UKThe University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, Scotland, UKThe University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, Scotland, UKTechnical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Munich, GermanyUniversity of Bern Institute of Social and Preventive Medicine, Bern, SwitzerlandEPPI Centre, UCL Social Research Institute, University College London, London, England, UKSouth African Medical Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, Western Cape, 7550, South AfricaThe University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, Scotland, UKDepartment of Psychiatry, University of Oxford, Oxford, England, UKEPPI Centre, UCL Social Research Institute, University College London, London, England, UKOxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, England, UKThe University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, Scotland, UKUniversity of Bern Institute of Social and Preventive Medicine, Bern, SwitzerlandOxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, England, UKSouth African Medical Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, Western Cape, 7550, South AfricaSouth African Medical Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, Western Cape, 7550, South AfricaDepartment of Psychiatry, University of Oxford, Oxford, England, UKSouth African Medical Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, Western Cape, 7550, South AfricaDepartment of Psychiatry, University of Oxford, Oxford, England, UKBackground Exercise for post-traumatic stress disorder (PTSD) is a potentially effective adjunct to psychotherapy. However, the biopsychosocial mechanisms of exercise are not well understood. This co-produced living systematic review synthesizes evidence from human and non-human studies. Methods We Included controlled human and non-human studies involving searches of multiple electronic databases (until 31.10.23). Records were screened, extracted, assessed for risk of bias, and reconciled by two independent reviewers. The primary outcome for human studies was PTSD symptom severity, while outcomes of interest for non-human studies included freezing behaviour, fear memory, fear generalization, startle response, and locomotion. Data were synthesised with random-effects meta-analysis. Results Eleven human studies met the eligibility criteria. Overall, exercise was not associated with symptom severity improvement compared to control (standardized mean difference [SMD] -0.08, 95% confidence interval [CI] -0.24 to 0.07; 8 studies, one at low risk of bias). High-intensity exercise reduced PTSD symptoms scores more than moderate-intensity exercise. There was insufficient data to examine the effects of exercise on functional impairment, PTSD symptom clusters, and PTSD remission. Only three studies, all at high risk of bias, examined mechanisms of exercise with inconclusive results. Exercise was associated with improvement in all behavioural outcomes, including locomotor activity (SMD 1.30, 95% CI 0.74 to 1.87, 14 studies), and changes in several neurobiological markers, including increase in brain-derived neurotrophic factor (SMD 1.79, 95% CI 0.56 to 3.01). Conclusions While non-human studies provide compelling evidence for the beneficial effects of exercise, human trials do not. Evidence from non-human studies suggest that exercise might increase the levels of brain-derived neurotrophic factor, enhance cognitive appraisal, and improve perceived exertion. Overall, the paucity of data on the effectiveness of exercise in PTSD and mechanisms of action underscore the need for rigorous trials. Registration The protocol was registered with PROSPERO (ID:453615; 22.08.2023).https://wellcomeopenresearch.org/articles/9-720/v3GALENOS PTSD exercise extinction learning memory regulation emotion regulationeng
spellingShingle David Gilbert
Thomy Tonia
Edoardo G. Ostinelli
Toshi A. Furukawa
Hossein Dehdarirad
Emily Sena
Fiona Ramage
Spyridon Siafis
Virginia Chiocchia
Claire Stansfield
Simonne Wright
Francesca Tinsdeall
Claire Friedrich
James Thomas
Charlotte Austin
Malcolm Macleod
Georgia Salanti
Jaycee Kennett
Soraya Seedat
Olufisayo Elugbadebo
Andrea Cipriani
Ouma Simple
Jennifer Potts
The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]
Wellcome Open Research
GALENOS
PTSD
exercise
extinction learning
memory regulation
emotion regulation
eng
title The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]
title_full The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]
title_fullStr The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]
title_full_unstemmed The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]
title_short The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies [version 3; peer review: 1 approved, 2 approved with reservations]
title_sort therapeutic potential of exercise in post traumatic stress disorder and its underlying mechanisms a living systematic review of human and non human studies version 3 peer review 1 approved 2 approved with reservations
topic GALENOS
PTSD
exercise
extinction learning
memory regulation
emotion regulation
eng
url https://wellcomeopenresearch.org/articles/9-720/v3
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