{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:11:26Z","timestamp":1772169086055,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.19903.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000}},{"DOI":"10.12688\/wellcomeopenres.19903.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000}}],"reference-count":84,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>Background Exercise can play an important role in reducing symptom severity and improving functional impairment in patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning the effect of exercise in PTSD management are not fully understood. This living systematic review aims to synthesize and triangulate the evidence from non-human and human studies to gain insight into the biopsychosocial mechanisms through which exercise reduces symptom severity and functional impairment. Methods Independent searches will be conducted in electronic databases to identify eligible studies. Two reviewers will independently conduct the study selection, data extraction, and risk of bias assessment. We will extract outcome data and variables that can act as effect modifiers or as mediators of the effect of exercise. For the non-human studies, outcome data will include the non-human equivalents of PTSD symptom clusters. For human studies, the primary outcome will be PTSD symptom severity. The secondary outcomes will be avoidance symptom severity, reexperiencing symptom severity, hyperarousal symptom severity, negative cognitions and mood severity, functional impairment, loss of PTSD diagnosis, and dropout rates. To explain the biopsychosocial mechanisms through which exercise affects the outcome of interest, we will extract effects that relate to the impact of exercise on potential mediating variables and the effect of the later outcomes. Comparison of within-study direct and indirect effects obtained from mediation analysis, when reported, will provide insight into the importance of the examined mediator. If appropriate, we will synthesize study results using meta-analyses. We will examine potential effect modifiers of the total exercise effect to understand better the impact of exercise on PTSD symptoms and function impairment (when possible). The evidence about the potential mediators of the association between exercise and PTSD-related outcomes will be considered in a consensus meeting when sufficient evidence is available. Protocol registration PROSPERO-ID: 453615<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.19903.3","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T12:55:06Z","timestamp":1744635306000},"page":"494","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms through which exercise reduces symptom severity and\/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-256X","authenticated-orcid":false,"given":"Simonne","family":"Wright","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2159-3776","authenticated-orcid":false,"given":"Toshi 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:30:10Z","timestamp":1752240610000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":84,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.19903.3","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/wellcomeopenres.19903.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/wellcomeopenres.19903.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.26151.r122222","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.26151.r122744","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.26151.r122222","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.26151.r122744","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.26151.r122222, Jony Sheynin, Texas A&M University, Houston, Texas, 25 Apr 2025, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3#referee-response-122222","order":0,"name":"referee-response-122222","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.22038.r106656, Courtney Bouchet, Colorado State University, Fort Collins, Colorado, 07 Jan 2025, version 1, 1 approved with reservations, 1 not approved","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v1#referee-response-106656","order":1,"name":"referee-response-106656","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Simonne Wright87<\/b>; \n<i>Posted: 24 Jan 2025<\/i>; \n<b>In&nbsp;<i>Mechanisms through which exercise reduces symptom severity and\/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies<\/i>, the authors outline detailed methods for a living systematic review. This includes various methods for exclusion and inclusion of experiments examining PTSD or PTSD-like behaviors and phenotypes in human and non-human studies, respectively. The methods outline how the data will be extracted from individual publications and strategies to reduce bias. Ultimately, while this is an important avenue of research for the inclusion of exercise as a treatment option for PTSD, this publication is not contributing to the literature and does not warrant an independent publication. This would be a suitable supplement for the living review itself or could be modified to be substantially shorter and included within the review as the methods section. <\/b> \n<b><u>Author response<\/u><\/b> Thank you for taking the time to review our protocol paper, \n<i>Mechanisms through which exercise reduces symptom severity and\/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies<\/i>. We respectfully disagree with the suggestion that the protocol paper does not warrant independent publication. Protocol papers are critical for maintaining transparency and accountability in systematic reviews. They provide a publicly accessible record of the planned methods and objectives, enabling readers to evaluate whether the living systematic review adheres to its original stated intent. This is particularly important for living reviews, where iterative updates are expected as new evidence emerges. Since the decision on whether protocols are suitable for publication in a journal depends on the journal's policies, it is important to highlight the policy of Wellcome Open Research regarding systematic review protocols: \u201cThe peer review focuses on whether the paper has full academic merit, not on interest or novelty, and we welcome protocols for any study design in these Wellcome-funded areas\u2026 Protocols for systematic reviews should be registered and must follow the PRISMA-P guidelines.\u201d (https:\/\/wellcomeopenresearch.org\/for-authors\/article-guidelines\/preparing-a-study-protocol-article) Publishing a protocol separately ensures that the review process is grounded in pre-specified plans, reducing the potential for selective reporting or unintentional deviations. It provides a detailed roadmap of the methods, including inclusion and exclusion criteria, data extraction strategies, and bias mitigation measures, thereby enhancing the rigor and credibility of the review. The protocol paper also facilitates replication by making the methodological framework accessible to other researchers providing a replicable model for future systematic reviews in PTSD and related fields. Furthermore, publishing the protocol allows for early engagement with peers, enabling constructive feedback that can improve the quality of the systematic review before its results are synthesized. This engagement aligns with the ethos of transparency and collaboration promoted by open-access platforms like Wellcome Open Research. Living systematic reviews are dynamic by nature, incorporating new evidence over time. A protocol serves as a stable reference point, ensuring that updates to the review remain aligned with the original methodological framework. Additionally, including an abridged version of the methods in the main review paper will not capture the depth of methodological detail or rationale that would be provided in a standalone protocol. Having a dedicated protocol allows readers to fully understand the rigor underlying the systematic review process. In light of these considerations, we believe that the independent publication of the protocol paper would significantly strengthen the transparency, reproducibility, and overall impact of our research. We hope this explanation underscores the importance of publishing the protocol in Wellcome Open Research.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3#referee-comment-6015","order":2,"name":"referee-comment-6015","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.26151.r122744, Cecila Hillard, Medical College of Wisconsin, Wisconsin, 23 May 2025, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-494\/v3#referee-response-122744","order":3,"name":"referee-response-122744","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"We are funded by Wellcome, a global charitable foundation. Edoardo G. Ostinelli is funded by the National Institute for Health and Care Research (NIHR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}