The therapeutic potential of exercise in post-traumatic stress disorder and its underlying mechanisms: A living systematic review of human and non-human studies.

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).Post-traumatic stress disorder (PTSD) is a mental health condition triggered by a traumatic event. It is characterised by symptoms such as reliving the trauma, nightmares, avoidance of trauma reminders, and heightened vigilance. Traditional treatments like Cognitive Behavioral Therapy (CBT) and Eye Movement Desensitization and Reprocessing (EMDR) are not effective for everyone, and relapse is common. Additionally, these treatments are costly and not widely accessible. Recently, exercise has been explored as a potential stand-alone or add-on treatment to improve PTSD outcomes and reduce relapse rates. We reviewed evidence from human and non-human studies for the effectiveness of exercise on PTSD symptoms and functioning. We also reviewed how exercise influences symptoms through biological factors, like brain-derived neurotrophic factor (BDNF), and psychosocial factors, such as cognitive appraisal and emotional state. In our search, we identified 11,870 human studies from multiple databases, of which 11 were deemed eligible. Of the human studies, three investigated responses to threat and BDNF levels, BDNF levels, and subjective feelings during exercise, respectively. For non-human studies, 1,222 records were found across eight databases, with 14 studies qualifying for inclusion. The non-human studies focused on various factors influencing PTSD treatment outcomes, including BDNF (8 studies), stress physiology (6 studies), and other brain and body changes (9 studies). Non-human studies find that exercise is effective for PTSD. Findings from human studies are not conclusive, although high-intensity exercise shows promise in reducing PTSD symptom severity. How exercise improves PTSD is still not well understood, although there is some evidence that exercise might work by increasing BDNF levels, enhancing cognitive appraisal, and improving perceived exertion. These findings underscore the need for further high-quality research to establish whether exercise enhances the effects of psychotherapy for PTSD and the mechanisms by which it does so.