Acute and chronic effects of physical exercise in inflammatory biomarkers in people with depression: A systematic review with meta-analysis.

People with depression have increased levels of pro-inflammatory cytokines compared to healthy subjects. Physical exercise can alleviate depressive symptoms and has anti-inflammatory properties. The aim of this study was to identify the effects of exercise on inflammatory biomarkers in people with depression. Clinical trials evaluating the acute and chronic effects of exercise on inflammatory biomarkers in adults with clinical depression were included. The search was conducted on the following databases: PubMed, Embase, Web of Science, PsycINFO, and SPORTDiscus. The risk of bias was assessed with the "Risk of bias in randomized trials" (RoB2) tool. Random effects meta-analyses estimated the acute and chronic effects of exercise for each marker separately. Heterogeneity was estimated with the l2 test. A total of 10 studies (497 participants) were included. No significant acute effects interleukins (IL)-6, IL-10, and IL-8 levels were found. Chronically, exercise increased the levels of TNF-α (Standardized Mean Difference = 0.296; 0.03-0.562, p = 0.029). No chronic effects were found for IL-6 and IL-1B. Overall, 90% of the studies had a moderate or high risk of bias. Exercise seems to promote a small increase in TNF-α, but literature is scarce and with a high risk of bias.

A transdiagnostic group exercise intervention for mental health outpatients in Germany (ImPuls): results of a pragmatic, multisite, block-randomised, phase 3 controlled trial.

BACKGROUND: Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders. METHODS: In this pragmatic, two-arm, multisite, randomised controlled trial in Germany, ten outpatient rehabilitative and medical care facilities were involved as study sites. Participants were outpatients diagnosed according to ICD-10 with one or more of the following disorders based on structured clinical interviews: moderate or severe depression, primary insomnia, post-traumatic stress disorder (PTSD), panic disorder, or agoraphobia. Participants were required to be aged between 18 years and 65 years, insured by the health insurers Allgemeine Ortskrankenkasse Baden-Württemberg or Techniker Krankenkasse, fluent in German, and without medical contraindications for exercise. Blocks of six participants were randomly allocated to ImPuls plus treatment-as-usual or treatment-as-usual alone (allocation ratio: 1:1), stratified by study site. The randomisation sequence was generated by an external data manager. The team responsible for data collection and management was masked to the randomisation sequence. The ImPuls intervention comprised evidence-based outdoor exercises lasting 30 min, and aimed at achieving at least moderate intensity. It also incorporated behavioural change techniques targeting motivational and volitional determinants of exercise behaviour. Treatment-as-usual was representative of typical outpatient health care in Germany, allowing patients access to any standard treatments. The primary outcome was global symptom severity at 6 months after randomisation, measured using self-report on the Brief Symptom Inventory (BSI-18) and analysed in the intention-to-treat sample. No individuals with lived experience of mental illness were involved in conducting the study or writing the final publication. Safety was assessed in all participants. The trial was registered with the German Clinical Trials Register (DRKS00024152) with a completion date of June 30, 2024. FINDINGS: 600 patients provided informed consent, were recruited to the study, and underwent a diagnostic interview between Jan 1, 2021, and May 31, 2022. Following this, 199 were excluded on the basis of inclusion and exclusion criteria and one withdrew consent during the baseline assessment. Of the 400 eligible participants, 284 (71%) self-identified as female, 106 (27%) self-identified as male, and nine (2%) self-identified as other. The mean age was 42·20 years (SD 13·23; range 19-65). Ethnicity data were not assessed. 287 (72%) participants met the criteria for moderate or severe depression, 81 (20%) for primary insomnia, 37 (9%) for agoraphobia, 46 (12%) for panic disorder, and 72 (18%) for PTSD. 199 participants were allocated to the intervention group of ImPuls plus treatment-as-usual and 201 to the control group of treatment-as-usual alone. 38 (19%) participants did not receive the minimum ImPuls intervention dose. ImPuls plus treatment-as-usual demonstrated superior efficacy to treatment-as-usual alone in reducing global symptom severity, with an adjusted difference on BSI-18 of 4·11 (95% CI 1·74-6·48; d=0·35 [95% CI 0·14-0·56]; p=0·0007) at 6 months. There were no significant differences in the total number of adverse events or serious adverse events between the two groups. There was one serious adverse event (male, torn ligament) related to the intervention. INTERPRETATION: ImPuls is an efficacious transdiagnostic adjunctive treatment in outpatient mental health care. Our findings suggest that exercise therapy should be implemented in outpatient mental health care as an adjunctive transdiagnostic treatment for mental disorders such as depression, insomnia, panic disorder, agoraphobia, and PTSD. Transdiagnostic group exercise interventions might ameliorate the existing disparity in care provision between the many individuals in need of evidence-based treatment and the few who are receiving it. FUNDING: The German Innovation Fund of the Federal Joint Committee of Germany.

The association of changes in leisure-time physical activity on depressive symptoms during Covid-19 in German adults: A longitudinal study.

This longitudinal survey assessed preventive and curative antidepressant effects of at least 75 min/week of leisure-time physical activity (LTPA) at different timepoints of the Covid-19 pandemic. We further investigated if high self-regulation skills were associated with higher odds of initiating or maintaining LTPA during the pandemic. Data was collected online from 4253 participants (age: m = 33.65 years, SD = 0.79; 79 % female) during the first quarantine measures in Germany (T1), as well as 4 weeks (T2), and 8 months (T3) later. We performed linear mixed models with changes (T2-T1, T3-T1) in LTPA and baseline major depressive disorder (MDD) as predictors (main effects and interaction effect) and depressive symptoms (at T2, T3) as the primary outcome. We found significant interaction effects of baseline depression and change in LTPA on depressive symptoms at T2 and T3 (p < 0.001). For probable cases of MDD an increasing LTPA to ≥75 min/week (vs. no change, <75 min/week) was associated with less depressive symptoms at T2 and T3 (p = 0.003, d = 0.28). For absence of depression at baseline, remaining at ≥75 min/week of LTPA was associated with less depressive symptoms at T2 and T3 compared to remaining at <75 min/week (p = 0.006, d = 0.11) or decreasing LTPA to <75 min/week (p = 0.018, d = 0.11). Reporting high self-regulation at T1 was associated with higher odds of performing ≥75 min/week of LTPA at T2/T3 (OR = 1.74, p < 0.001). In general, studies report reduced LTPA during Covid-19. To benefit from the reported preventive and interventional effects, further interventions should focus on improving physical activity related self-regulation to identify and overcome barriers for LTPA.

Long-term efficacy of exercise across diagnostically heterogenous mental disorders and the mediating role of affect regulation skills.

BACKGROUND: Exercise interventions are efficacious in reducing disorder-specific symptoms in various mental disorders. However, little is known about long-term transdiagnostic efficacy of exercise across heterogenous mental disorders and the potential mechanisms underlying treatment effects. METHODS: Physically inactive outpatients, with depressive disorders, anxiety disorders, insomnia or attention deficit hyperactivity disorder were randomized to a standardized 12-week exercise intervention, combining moderate exercise with behavior change techniques (BCTs) (n = 38), or a passive control group (n = 36). Primary outcome was global symptom severity (Symptom Checklist-90, SCL-90-R) and secondary outcomes were self-reported exercise (Physical Activity, Exercise, and Sport Questionnaire), exercise-specific affect regulation (Physical Activity-related Health Competence Questionnaire) and depression (SCL-90-R) assessed at baseline (T1), post-treatment (T2) and one year after post-treatment (T3). Intention-to-treat analyses were conducted using linear mixed models and structural equations modeling. RESULTS: From T1 to T3, the intervention group significantly improved on global symptom severity (d = -0.43, p = .031), depression among a depressed subsample (d = -0.62, p = .014), exercise (d = 0.45, p = .011) and exercise-specific affect regulation (d = 0.44, p = .028) relative to the control group. The intervention group was more likely to reveal clinically significant changes from T1 to T3 (p = .033). Increases in exercise-specific affect regulation mediated intervention effects on global symptom severity (ß = -0.28, p = .037) and clinically significant changes (ß = -0.24, p = .042). CONCLUSIONS: The exercise intervention showed long-term efficacy among a diagnostically heterogeneous outpatient sample and led to long-lasting exercise behavior change. Long-term increases in exercise-specific affect regulation within exercise interventions seem to be essential for long-lasting symptom reduction.

Concept and study protocol of the process evaluation of a pragmatic randomized controlled trial to promote physical activity in outpatients with heterogeneous mental disorders-the ImPuls study.

BACKGROUND: Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. METHODS: The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis. DISCUSSION: The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system. TRIAL REGISTRATION: The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152 ).

The effect of exercise and affect regulation skills on mental health during the COVID-19 pandemic: A cross-sectional survey.

BACKGROUND: COVID-19-related confinements pose a threat to mental health. We investigated prevalence rates of symptoms of depression, generalized anxiety and insomnia in German adults. Furthermore, we explored associations of exercise behavior with disorder-specific symptoms and assessed whether specific affect regulation skills enhance the effect of exercise on symptom alleviation. METHODS: Cross-sectional survey-based data collected during the first lockdown is presented: 4268 adults completed questionnaires on mental health, exercise behavior and Covid-related lifestyle factors. Primary outcome was depression (PHQ-9), secondary outcomes generalized anxiety (PHQ-D) and sleep quality (PSQI). Multiple linear regression analyses were performed to examine the association of exercise behavior with the outcomes. RESULTS: Analyses resulted in elevated symptoms of psychological distress (probable cases of depressive disorder: 31.2%, anxiety disorder: 7.5%, sleeping disorder: 43.0%). A change towards less exercise during the lockdown was significantly associated with higher levels of depression (t=5.269; ß=0.077, p<.001), anxiety (t=3.397; ß=0.055, p<.001) and insomnia (t=3.466; ß=0.058; p<.001). Physical activity (PA)-related affect regulation enhanced the effect of exercise on mental health. CONCLUSION: Results suggest a demand for measures which promote the maintenance of exercise during a pandemic and improve PA-related affect regulation to optimize effects of exercise on mental health.

The Efficacy of Physical Activity for Children with Attention Deficit Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: This systematic review and meta-analysis assesses the efficacy of regular, moderate to vigorous physical activity (MVPA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents in randomized controlled trials (RCTs). METHODS: RCTs including children and adolescents with clinically diagnosed ADHD, implementing regular MVPA, and assessing ADHD core-symptoms on a valid rating scale post-intervention (primary outcome) were included. Outcomes were pooled through random-effects meta-analysis. Prospero registration: CRD42019142166. RESULTS: MVPA had a small effect on total ADHD core symptoms (n = 11; g = -0.33; 95% CI [-0.63; -0.02]; p = .037). CONCLUSIONS: MVPA could serve as an alternative treatment for ADHD. New RCTs are necessary to increase the understanding of the effect regarding frequency, intensity, type of MVPA interventions, and differential effects on age groups.

Efficacy and cost-effectiveness of a Transdiagnostic group-based exercise intervention: study protocol for a pragmatic multi-site randomized controlled trial.

BACKGROUND: Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD). METHODS: This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and cost-effectiveness of the manualized, group-based six-months exercise intervention "ImPuls", among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be block-randomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be self-reported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and cost-utility ratios. DISCUSSION: Despite its promising therapeutic effects, exercise programs are currently not provided within the outpatient mental health care system in Germany. This trial will inform service providers and policy makers about the efficacy and cost-effectiveness of the group-based exercise intervention ImPuls within a naturalistic outpatient health care setting. Group-based exercise interventions might provide an option to close the treatment gap within outpatient mental health care settings. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (ID: DRKS00024152 , 05/02/2021).

Transdiagnostic efficacy of a group exercise intervention for outpatients with heterogenous psychiatric disorders: a randomized controlled trial.

BACKGROUND: Exercise efficaciously reduces disorder-specific symptoms of psychiatric disorders. The current study aimed to examine the efficacy of a group exercise intervention on global symptom severity and disorder-specific symptoms among a mixed outpatient sample. METHODS: Groups of inactive outpatients, waiting for psychotherapy, with depressive disorders, anxiety disorders, insomnia, and attention-deficit/hyperactivity disorders were randomized to a manualized 12-week exercise intervention, combining moderate to vigorous aerobic exercise with techniques for sustainable exercise behaviour change (n = 38, female = 71.1% (n = 27), Mage = 36.66), or a passive control group (n = 36, female = 75.0% (n = 27), Mage = 34.33). Primary outcomes were global symptom severity and disorder-specific symptoms, measured with the Symptom Checklist-90-Revised and Pittsburgh Sleep Quality Index pre- and post-treatment. Secondary outcome was the self-reported amount of exercise (Physical Activity, Exercise, and Sport Questionnaire), measured pre-treatment, intermediate-, and post-treatment. Intention-to-treat analyses were conducted using linear mixed models. Linear regressions were conducted to examine the effect of the change of exercise behaviour on the change of symptoms. RESULTS: The intervention significantly improved global symptom severity (d = 0.77, p = .007), depression (d = 0.68, p = .015), anxiety (d = 0.87, p = .002), sleep quality (d = 0.88, p = .001), and increased the amount of exercise (d = 0.82, p < .001), compared to the control group. Post-treatment differences between groups were significant for depression (d = 0.63, p = .031), sleep quality (d = 0.61, p = .035) and the amount of exercise (d = 1.45, p < .001). Across both groups, the reduction of global symptom severity was significantly predicted by an increase of exercise (b = .35, p = .012). CONCLUSIONS: The exercise intervention showed transdiagnostic efficacy among a heterogeneous clinical sample in a realistic outpatient setting and led to sustained exercise behaviour change. Exercise may serve as an efficacious and feasible transdiagnostic treatment option improving the existing treatment gap within outpatient mental health care settings. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (ID: NCT03542396 , 25/04/2018).

Is Physical Activity Associated with Less Depression and Anxiety During the COVID-19 Pandemic? A Rapid Systematic Review.

BACKGROUND: The Covid-19 pandemic is affecting the entire world population. During the first spread, most governments have implemented quarantine and strict social distancing procedures. Similar measures during recent pandemics resulted in an increase in post-traumatic stress, anxiety and depression symptoms. The development of novel interventions to mitigate the mental health burden are of utmost importance. OBJECTIVE: In this rapid review, we aimed to provide a systematic overview of the literature with regard to associations between physical activity (PA) and depression and anxiety during the COVID-19 pandemic. DATA SOURCE: We searched major databases (PubMed, EMBASE, SPORTDiscus, and Web of Science) and preprint servers (MedRxiv, SportRxiv, ResearchGate, and Google Scholar), for relevant papers up to 25/07/2020. STUDY ELIGIBILITY CRITERIA: We included observational studies with cross-sectional and longitudinal designs. To qualify for inclusion in the review, studies must have tested the association of PA with depression or anxiety, using linear or logistic regressions. Depression and anxiety must have been assessed using validated rating scales. STUDY APPRAISAL AND SYNTHESIS METHODS: Effect sizes were represented by fully adjusted standardized betas and odds ratios (OR) alongside 95% confidence intervals (CI). In case standardized effects could not be obtained, unstandardized effects were presented and indicated. RESULTS: We identified a total of 21 observational studies (4 longitudinal, 1 cross-sectional with retrospective analysis, and 16 cross-sectional), including information of 42,293 (age 6-70 years, median female = 68%) participants from five continents. The early evidence suggests that people who performed PA on a regular basis with higher volume and frequency and kept the PA routines stable, showed less symptoms of depression and anxiety. For instance, those reporting a higher total time spent in moderate to vigorous PA had 12-32% lower chances of presenting depressive symptoms and 15-34% of presenting anxiety. CONCLUSION: Performing PA during Covid-19 is associated with less depression and anxiety. To maintain PA routines during Covid-19, specific volitional and motivational skills might be paramount to overcome Covid-19 specific barriers. Particularly, web-based technologies could be an accessible way to increase motivation and volition for PA and maintain daily PA routines.