Cited by 409Physical Activity and HealthTreatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

The DOI matches its Crossref record; 101 of the 101 references it cites were found in a registry or an index; none of the 96 sources its claims cite is checked for support yet.

The Role of Exercise in Management of Mental Health Disorders: An Integrative Review

Open access
Smith, Patrick J., Merwin, Rhonda M.·2021·Annual Review of Medicine

Abstract

A large and growing body of evidence suggests that physical activity (PA) may hold therapeutic promise in the management of mental health disorders. Most evidence linking PA to mental health outcomes has focused on the effects of aerobic exercise training on depression, although a growing body of work supports the efficacy of both aerobic and resistance exercise paradigms in the treatment of anxiety and post-traumatic stress disorder. Despite abundant evidence linking PA and mental health, use of exercise training as a mental health treatment remains limited due to three important sources of uncertainty: ( a) large individual differences in response to exercise treatment within multiple mental health domains; ( b) the critical importance of sustained PA engagement, not always achieved, for therapeutic benefit; and ( c) disagreement regarding the relative importance of putative therapeutic mechanisms. Our review of treatment data on exercise interventions and mental health outcomes focuses primarily on depression and anxiety within a health neuroscience framework. Within this conceptual framework, neurobiological and behavioral mechanisms may have additiveor synergistic influences on key cognitive and behavioral processes that influence mental health outcomes. We therefore highlight sources of treatment heterogeneity by integrating the critical influences of ( a) neurobiological mechanisms enhancing neuroplasticity and ( b) behavioral learning of self-regulatory skills. Understanding the interrelationships between dynamic neurobiological and behavioral mechanisms may help inform personalized mental health treatments and clarify why, and for whom, exercise improves mental health outcomes. The review concludes with recommendations for future studies leveraging individual differences to refine treatment approaches to optimize mental health benefits.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This integrative review argues that aerobic and resistance exercise training hold therapeutic promise for mental health, especially depression and anxiety, through synergistic neurobiological and behavioral mechanisms. It emphasizes that treatment response is heterogeneous and long-term benefit depends on sustained physical activity engagement.

Key findings

  • Epidemiological evidence links higher physical activity to lower odds of depression (OR = 0.83, 95% CI 0.79–0.88), elevated anxiety symptoms (OR = 0.87, 95% CI 0.77–0.99), and anxiety disorders (OR = 0.66, 95% CI 0.53–0.83).
  • Exercise trials generally show moderate-to-large improvements: aerobic exercise versus no intervention ES = 1.24 and versus conventional control ES = 0.68, but effects decline at follow-up (ES = 0.22); resistance training for depressive symptoms ES = 0.66 (95% CI 0.48–0.83).
  • Exercise as an add-on therapy enhanced conventional outpatient treatment over 2–3 months (ES = −0.79, 95% CI −1.01 to −0.57), and in late-life depression a meta-analysis of nine trials and 1,308 participants found ES = 0.64 (95% CI 0.27–1.01) with significant heterogeneity.
  • Proposed mechanisms include neuroplasticity facilitators such as BDNF, VEGF, and IGF-1; brain network changes in salience, executive control, and default mode networks; and behavioral mechanisms including emotion regulation, cognitive control, self-efficacy (exercise interventions ES = 0.59), and reinforcement/reward.

Methods

  • Design: integrative/narrative review of treatment data on exercise interventions and mental health outcomes, focused primarily on depression and anxiety within a health neuroscience framework.
  • Data: synthesizes epidemiological studies, randomized controlled trials, meta-analyses, neuroimaging/connectivity findings, and behavioral mechanism research, including populations such as adults with depression, late-life depression, anxiety, and other clinical samples.
  • Analysis: conceptual synthesis integrating neurobiological mechanisms (neuroplasticity, growth factors, inflammation, brain networks, neurotransmitters) with behavioral mechanisms (emotion regulation, cognitive control, self-efficacy, reinforcement) to explain heterogeneity and inform personalized treatment.

Limitations

  • The paper explicitly identifies three sources of uncertainty: large individual differences in response to exercise treatment, the critical importance of sustained physical activity engagement for therapeutic benefit, and disagreement regarding the relative importance of putative therapeutic mechanisms.
  • The paper states that there is a lack of explanatory studies delineating for whom and why exercise is beneficial, and notes significant heterogeneity across trials and populations, including some large multisite trials failing to find benefit in late-life depression.
  • Evident from the text: this is an integrative review rather than a systematic review with a described formal search strategy, quality appraisal, or quantitative pooling, so conclusions rely on narrative synthesis across heterogeneous studies.

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Integrity signals

Registry

Crossref · 10.1146/annurev-med-060619-022943

Cites

101 of 101 references verified0 citation errors · 0 not checkable

Statistics

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Verification

Claims the paper makes

71 Not checked yet · 32 Own interpretation · 17 No basis given

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Show all 54 claims

  • It may state two separate claims as one. 55
  • Probably not a substantial claim. 15
66 of 66
  • The paper relies on this without support.

    The brain’s capacity for neurobiological remodeling within key neurocircuitry is impaired across many heterogeneous mental health conditions, declines with age, and may be inhibited by several age-related systemic processes.

    “The brain’s capacity for neurobiological remodeling within key neurocircuitry is a critical element of adaptive learning, is impaired across many heterogeneous mental health conditions, declines with age, and may be inhibited by several age-related systemic processes.”
  • The paper relies on this without support.

    Adaptive learning is a critical element of mental health improvements following behavioral interventions.

    “Adaptive learning, in turn, is a critical element of mental health improvements following behavioral interventions.”
  • The paper relies on this without support.

    Exercise is one of the few behavioral processes that appears to increase neuroplasticity.

    “Exercise is one of the few behavioral processes that appears to increase neuroplasticity.”
  • The paper relies on this without support.

    Several key systemic factors must be present to facilitate neuroplastic changes, all of which are modifiable through exercise training: neurotrophins, intact cerebral metabolic function, low neuroinflammation, and sleep.

    “Several key systemic factors must be present to facilitate neuroplastic changes, all of which are modifiable through exercise training. Briefly, these include neurotrophins, intact cerebral metabolic function, low neuroinflammation, and sleep.”
  • The paper relies on this without support.

    Effective behavioral engagement and self-monitoring are frequently impaired in individuals with depression and anxiety.

    “As detailed below, effective behavioral engagement and self-monitoring are frequently impaired in individuals with depression and anxiety.”
  • The paper relies on this without support.

    Conventional exercise training programs teach participants to identify and implement SMART goals to optimize exercise participation and maintenance.

    “Conventional exercise training programs teach participants to identify and implement goals that are specific, measurable, achievable, realistic, and timely (SMART goals), in order to optimize exercise participation and maintenance.”
  • The paper relies on this without support.

    Through setting SMART goals, striving toward them, and evaluating iterative progress, participants cultivate realistic expectations for themselves and internalize a sense of behavioral control.

    “Through the process of setting SMART goals, striving toward them, and evaluating iterative progress, participants cultivate realistic expectations for themselves and internalize a sense of behavioral control.”
  • The paper relies on this without support.

    Realistic goal setting and attainment contribute to emotion regulation by increasing self-mastery, increasing agency, and establishing new, positive associations with self-concept.

    “Realistic goal setting and attainment also contribute to ER by increasing self-mastery, increasing agency, and establishing new, positive associations with self-concept.”
  • The paper relies on this without support.

    Self-monitoring may build a greater capacity to identify and repeat effective behaviors and to identify maladaptive behavioral patterns.

    “The process of self-monitoring (tracking behavior and its consequences) may also build a greater capacity to identify and repeat behaviors that are effective, as well as identifying maladaptive behavioral patterns.”
  • The paper relies on this without support.

    Sustained attention and vigilance are impaired across many mental health conditions, particularly in depression, where patients have difficulties sustaining engagement toward goal-directed targets over prolonged periods.

    “Sustained attention and vigilance are also impaired across many mental health conditions, particularly in depression, where patients have difficulties sustaining engagement toward goal-directed targets over prolonged periods of time.”
  • The paper relies on this without support.

    Competing cognitive processes, such as rumination or excessive worry, may divert attention away from effective task performance and increase emotional suffering.

    “Competing cognitive processes, such as rumination or excessive worry, may divert attention away from effective task performance and increase emotional suffering.”
  • The paper relies on this without support.

    Effective engagement in an exercise activity requires full attention to the task and awareness of a narrowed set of stimuli.

    “In this case, effective engagement in the activity requires full attention to the task and awareness of a narrowed set of stimuli (e.g., one’s breathing and ability to pace breathing).”
  • The paper relies on this without support.

    A poverty of reinforcement or adaptive reward may lead to increased negative affect (e.g., depression) or the development of maladaptive behavior patterns to increase positive feelings (e.g., substance abuse).

    “A poverty of reinforcement or adaptive reward may lead to increased negative affect (e.g., depression) or the development of maladaptive behavior patterns to increase positive feelings (e.g., substance abuse).”
  • The paper relies on this without support.

    Newer CBTs, such as Acceptance and Commitment Therapy, link behavioral activation specifically to personal values, which may function to augment its reinforcement value or function as an establishing operation, and/or help sustain activity engagement.

    “Newer CBTs, such as Acceptance and Commitment Therapy, link behavioral activation specifically to personal values, which may function to augment its reinforcement value or function as an establishing operation, and/or help sustain activity engagement.”
  • The paper relies on this without support.

    Dysfunctional reward sensitivity is a core feature increasing the risk of depression and serves as a key barrier to implementation of many therapeutic interventions.

    “Dysfunctional reward sensitivity is a core feature increasing the risk of depression and serves as a key barrier to implementation of many therapeutic interventions.”
  • The paper relies on this without support.

    Several newer CBTs teach mindfulness to decrease engagement in unproductive mental activities and improve capacity to be in the present moment.

    “Several newer CBTs teach mindfulness to decrease engagement in unproductive mental activities and improve capacity to be in the present moment.”
16 of 16

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Citations

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  1. Voss MW, 2010, Front. Aging Neurosci., 2, 32

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Metadata

Authors
Smith, P. J., & Merwin, R. M.
Affiliations
  • Duke University (US)
  • Department of Psychiatry and Behavioral Sciences,
Venue
Annual Review of Medicine
Published
2021-01-27
Volume
72
Issue
1
Pages
45-62
ISSN
  • 0066-4219 (ISSN-L)
  • 1545-326X
OpenAlex
W3108397702
Cited by
360
References
101
Citations by year
2026: 81 · 2025: 121 · 2024: 83 · 2023: 45 · 2022: 25 · 2021: 5
FWCI
2.39
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL130237)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
physical activity, mental illness, depression, anxiety, post-traumatic stress disorder, aerobic exercise, resistance training, neuroplasticity, self-regulation, individual differences, treatment effect heterogeneity, exercise adherence, personalized treatment
MeSH terms
Mental Disorders, Exercise Therapy, Humans, Mental Health, Psychotherapy, Quality of Life, Exercise

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