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British Journal of Sports Medicine Aug 2023To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and the presence of publication bias.
DESIGN
Systematic review and meta-analysis with meta-regression.
DATA SOURCES
The Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, Embase, SPORTDiscus, PsycINFO, Scopus and Web of Science were searched without language restrictions from inception to 13 September2022 (PROSPERO registration no CRD42020210651).
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials including participants aged 18 years or older with a diagnosis of major depressive disorder or those with depressive symptoms determined by validated screening measures scoring above the threshold value, investigating the effects of an exercise intervention (aerobic and/or resistance exercise) compared with a non-exercising control group.
RESULTS
Forty-one studies, comprising 2264 participants post intervention were included in the meta-analysis demonstrating large effects (standardised mean difference (SMD)=-0.946, 95% CI -1.18 to -0.71) favouring exercise interventions which corresponds to the number needed to treat (NNT)=2 (95% CI 1.68 to 2.59). Large effects were found in studies with individuals with major depressive disorder (SMD=-0.998, 95% CI -1.39 to -0.61, k=20), supervised exercise interventions (SMD=-1.026, 95% CI -1.28 to -0.77, k=40) and moderate effects when analyses were restricted to low risk of bias studies (SMD=-0.666, 95% CI -0.99 to -0.34, k=12, NNT=2.8 (95% CI 1.94 to 5.22)).
CONCLUSION
Exercise is efficacious in treating depression and depressive symptoms and should be offered as an evidence-based treatment option focusing on supervised and group exercise with moderate intensity and aerobic exercise regimes. The small sample sizes of many trials and high heterogeneity in methods should be considered when interpreting the results.
Topics: Humans; Depression; Depressive Disorder, Major; Exercise; Exercise Therapy
PubMed: 36731907
DOI: 10.1136/bjsports-2022-106282 -
The American Journal of Medicine Sep 2023Cardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular disease. In particular, major depression has been linked to increased all-cause mortality, development of cardiovascular disease, and worse outcomes in those with existing cardiovascular disease.
METHODS
We conducted a meta-analysis assessing the incidence of cardiovascular disease and cardiovascular disease outcomes among those with major depressive disorder.
RESULTS
Among 26 studies of 1,957,621 individuals, depression was associated with increased risk of incident stroke (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.00-1.28), myocardial infarction (HR 1.28; 95% CI, 1.14-1.45), congestive heart failure (HR 1.04; 95% CI, 1.00-1.09), or any cardiovascular disease (HR 1.16; 95% CI, 1.04-1.30). Depression was associated with increased risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63), and congestive heart failure mortality (HR 3.20; 95% CI, 1.29-7.94).
CONCLUSION
Depression has a significant negative impact on development of cardiovascular disease and on cardiovascular disease outcomes. Further efforts to understand and mitigate these impacts are prudent.
Topics: Humans; Cardiovascular Diseases; Depression; Risk Factors; Depressive Disorder, Major; Heart Failure
PubMed: 37247751
DOI: 10.1016/j.amjmed.2023.04.036 -
The World Journal of Biological... 2023Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the... (Review)
Review
Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ketamine, esketamine and r-ketamine for unipolar and bipolar depression. Electronic databases were searched from inception to September 2022 to identify relevant articles. Twenty-two studies, including four randomized clinical trials (RCTs), one case series, six case reports, five open-label trials and six retrospective chart review studies involving 2336 patients with depression were included. All included studies reported significant improvement following ketamine administration. Ketamine was well tolerated without serious adverse events. However, RCTs had a high risk of bias due to analysis methods and adverse events monitoring. Ketamine dosage varied from 0.5 to 1.25 mg/kg. The frequency of administration was daily to monthly. Several important limitations were identified, most notably the small number of RCTs. Taken together, preliminary evidence suggests the potential for antidepressant effect of oral ketamine. However, further research with large sample size and long follow-up period is needed to better determine the antisuicidal effect and efficacy in treatment-resistant depression.
Topics: Humans; Ketamine; Depression; Excitatory Amino Acid Antagonists; Bipolar Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
PubMed: 36651238
DOI: 10.1080/15622975.2023.2169349 -
Neuron Jul 2023Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established...
Although the etiology of major depressive disorder remains poorly understood, reduced gamma oscillations is an emerging biomarker. Olfactory bulbectomy, an established model of depression that reduces limbic gamma oscillations, suffers from non-specific effects of structural damage. Here, we show that transient functional suppression of olfactory bulb neurons or their piriform cortex efferents decreased gamma oscillation power in limbic areas and induced depression-like behaviors in rodents. Enhancing transmission of gamma oscillations from olfactory bulb to limbic structures by closed-loop electrical neuromodulation alleviated these behaviors. By contrast, silencing gamma transmission by anti-phase closed-loop stimulation strengthened depression-like behaviors in naive animals. These induced behaviors were neutralized by ketamine treatment that restored limbic gamma power. Taken together, our results reveal a causal link between limbic gamma oscillations and depression-like behaviors in rodents. Interfering with these endogenous rhythms can affect behaviors in rodent models of depression, suggesting that restoring gamma oscillations may alleviate depressive symptoms.
Topics: Animals; Olfactory Bulb; Rodentia; Depression; Depressive Disorder, Major; Neurons
PubMed: 37164008
DOI: 10.1016/j.neuron.2023.04.013 -
The New England Journal of Medicine Feb 2024A 67-year-old woman with a history of obesity, chronic low back pain, and recurrent episodes of major depression presents with mild depressive symptoms of more than 2... (Review)
Review
A 67-year-old woman with a history of obesity, chronic low back pain, and recurrent episodes of major depression presents with mild depressive symptoms of more than 2 years’ duration, with worsening symptoms over the past 4 months. She was receiving sertraline at a stable dose of 100 mg per day until 3 months ago, when she initially presented for her worsening depressive symptoms. At that time, sertraline was tapered off, and treatment with extra-long extended-release bupropion (bupropion XL) was started at a dose of 150 mg daily and was increased to 300 mg daily 3 weeks later. Despite having taken the higher dose of bupropion XL for more than 2 months, the patient continues to have low mood, loss of interest in usual pleasurable activities, trouble falling asleep, wakefulness several times during the night, diminished energy, poor appetite, difficulty concentrating, and intrusive thoughts of being “better off dead,” but she does not have active suicidal thinking. Her nine-question Patient Health Questionnaire (PHQ-9) score is 17 (on a scale of 0 to 27, with higher scores indicating greater severity of depressive symptoms). How would you evaluate and treat this patient?
Topics: Humans; Aged; Depression; Depressive Disorder, Treatment-Resistant; Treatment Outcome
PubMed: 38354142
DOI: 10.1056/NEJMcp2305428 -
BMC Medicine Sep 2023Major depressive disorder (MDD) has a significant impact on global burden of disease. Complications in clinical management can occur when response to pharmacological...
BACKGROUND
Major depressive disorder (MDD) has a significant impact on global burden of disease. Complications in clinical management can occur when response to pharmacological modalities is considered inadequate and symptoms persist (treatment-resistant depression (TRD)). We aim to investigate inflammation, proxied by C-reactive protein (CRP) levels, and body mass index (BMI) as putative causal risk factors for depression and subsequent treatment resistance, leveraging genetic information to avoid confounding via Mendelian randomisation (MR).
METHODS
We used the European UK Biobank subcohort ([Formula: see text]), the mental health questionnaire (MHQ) and clinical records. For treatment resistance, a previously curated phenotype based on general practitioner (GP) records and prescription data was employed. We applied univariable and multivariable MR models to genetically predict the exposures and assess their causal contribution to a range of depression outcomes. We used a range of univariable, multivariable and mediation MR models techniques to address our research question with maximum rigour. In addition, we developed a novel statistical procedure to apply pleiotropy-robust multivariable MR to one sample data and employed a Bayesian bootstrap procedure to accurately quantify estimate uncertainty in mediation analysis which outperforms standard approaches in sparse binary outcomes. Given the flexibility of the one-sample design, we evaluated age and sex as moderators of the effects.
RESULTS
In univariable MR models, genetically predicted BMI was positively associated with depression outcomes, including MDD ([Formula: see text] ([Formula: see text] CI): 0.133(0.072, 0.205)) and TRD (0.347(0.002, 0.682)), with a larger magnitude in females and with age acting as a moderator of the effect of BMI on severity of depression (0.22(0.050, 0.389)). Multivariable MR analyses suggested an independent causal effect of BMI on TRD not through CRP (0.395(0.004, 0.732)). Our mediation analyses suggested that the effect of CRP on severity of depression was partly mediated by BMI. Individuals with TRD ([Formula: see text]) observationally had higher CRP and BMI compared with individuals with MDD alone and healthy controls.
DISCUSSION
Our work supports the assertion that BMI exerts a causal effect on a range of clinical and questionnaire-based depression phenotypes, with the effect being stronger in females and in younger individuals. We show that this effect is independent of inflammation proxied by CRP levels as the effects of CRP do not persist when jointly estimated with BMI. This is consistent with previous evidence suggesting that overweight contributed to depression even in the absence of any metabolic consequences. It appears that BMI exerts an effect on TRD that persists when we account for BMI influencing MDD.
Topics: Female; Humans; Body Mass Index; Depressive Disorder, Major; Bayes Theorem; Depression; Inflammation
PubMed: 37710313
DOI: 10.1186/s12916-023-03001-7 -
Nature Reviews. Rheumatology Dec 2023Depression is a common and disabling comorbidity in rheumatoid arthritis that not only decreases the likelihood of remission and treatment adherence but also increases... (Review)
Review
Depression is a common and disabling comorbidity in rheumatoid arthritis that not only decreases the likelihood of remission and treatment adherence but also increases the risk of disability and mortality in patients with rheumatoid arthritis. Compelling data that link immune mechanisms to major depressive disorder indicate possible common mechanisms that drive the pathology of the two conditions. Preclinical evidence suggests that pro-inflammatory cytokines, which are prevalent in rheumatoid arthritis, have various effects on monoaminergic neurotransmission, neurotrophic factors and measures of synaptic plasticity. Neuroimaging studies provide insight into the consequences of inflammation on the brain (for example, on neural connectivity), and clinical trial data highlight the beneficial effects of immune modulation on comorbid depression. Major depressive disorder occurs more frequently in patients with rheumatoid arthritis than in the general population, and major depressive disorder also increases the risk of a future diagnosis of rheumatoid arthritis, further highlighting the link between rheumatoid arthritis and major depressive disorder. This Review focuses on interactions between peripheral and central immunobiological mechanisms in the context of both rheumatoid arthritis and major depressive disorder. Understanding these mechanisms will provide a basis for future therapeutic development, not least in depression.
Topics: Humans; Depression; Depressive Disorder, Major; Arthritis, Rheumatoid; Comorbidity; Inflammation
PubMed: 37923863
DOI: 10.1038/s41584-023-01037-w -
JAMA Psychiatry Jul 2023Depression is associated with an increased risk of physical illness, but the most common causes of hospitalization among people with depression are unclear.
IMPORTANCE
Depression is associated with an increased risk of physical illness, but the most common causes of hospitalization among people with depression are unclear.
OBJECTIVE
To examine the association of depression with an array of physical conditions requiring hospital treatment.
DESIGN, SETTING, AND PARTICIPANTS
In this outcomewide prospective multicohort study, primary analysis was based on data from the UK Biobank, a population-based study in the United Kingdom. Analyses were repeated in an independent data set of 2 cohorts in Finland, a population-based study and an occupational cohort. Data analysis was conducted between April and September 2022.
EXPOSURES
Self-reported depression, recurrent severe major depression, recurrent moderate major depression, and a single major depressive episode.
MAIN OUTCOMES AND MEASURES
A total of 77 common health conditions ascertained from linkage data to national hospital and mortality registries.
RESULTS
The analytical sample of UK Biobank participants consisted of 130 652 individuals (71 565 women [54.8%]; 59 087 men [45.2%]; mean [SD] age at baseline, 63.3 [7.8] years). The pooled data from the Finnish replication cohorts included 109 781 participants (82 921 women [78.6%]; 26 860 men [21.4%]; mean [SD] age, 42 [10.8] years). In the main analysis, severe/moderately severe depression was associated with the incidence of 29 nonoverlapping conditions requiring hospital treatment during a 5-year follow-up. Twenty-five of these associations remained after adjustment for confounders and multiple testing (adjusted hazard ratio [HR] range, 1.52-23.03) and were confirmed in the analysis of the Finnish cohorts. These included sleep disorders (HR, 5.97; 95% CI, 3.27-10.89), diabetes (HR, 5.15; 95% CI, 2.52-10.50), ischemic heart disease (HR, 1.76; 95% CI, 1.36-2.29), chronic obstructive bronchitis (HR, 4.11; 95% CI, 2.56-6.60), bacterial infections (HR, 2.52; 95% CI, 1.99-3.19), back pain (HR, 3.99; 95% CI, 2.96-5.38), and osteoarthritis (HR, 1.80; 95% CI, 1.46-2.20). The highest cumulative incidence was observed for endocrine and related internal organ diseases (245 per 1000 persons with depression; risk difference relative to unaffected individuals: 9.8%), musculoskeletal diseases (91 per 1000 persons; risk difference, 3.7%), and diseases of the circulatory system and blood (86 per 1000 persons; risk difference, 3.9%). The cumulative incidence was lower for hospital-treated mental, behavioral, and neurological disorders (20 in 1000 persons; risk difference, 1.7%). Depression was also associated with disease progression in people with prevalent heart disease or diabetes, and for 12 conditions, there was evidence of a bidirectional relationship.
CONCLUSIONS AND RELEVANCE
In this study, the most common causes of hospitalization in people with depression were endocrine, musculoskeletal, and vascular diseases, not psychiatric disorders. These findings suggest that depression should be considered as a target for the prevention of physical and mental disease.
Topics: Male; Humans; Female; Adult; Child; Prospective Studies; Depression; Depressive Disorder, Major; Diabetes Mellitus; Hospitalization; Risk Factors
PubMed: 37133850
DOI: 10.1001/jamapsychiatry.2023.0777 -
Psychiatry Research Aug 2023Evidence supports the antidepressant effects of resistance exercise training (RET); however, findings among young adults at-risk for elevated depressive symptoms are... (Randomized Controlled Trial)
Randomized Controlled Trial
Evidence supports the antidepressant effects of resistance exercise training (RET); however, findings among young adults at-risk for elevated depressive symptoms are limited. This randomized controlled trial examined the effects of eight weeks of ecologically-valid, guidelines-based RET, compared to a wait-list control, on depressive symptoms among 55 young adults (26±5y; 36 female) with and without subclinical, or analogue, Generalized Anxiety Disorder (AGAD; Psychiatric Diagnostic Screening Questionnaire GAD subscale ≥6 and Penn State Worry Questionnaire ≥45) and Major Depressive Disorder (AMDD). Following a three-week familiarization period, participants completed one-on-one, twice-weekly RET sessions. The 16-item, self-reported Quick Inventory of Depressive Symptomatology (QIDS) assessed depressive symptoms. RM-ANCOVAs examined between-group differences, and significant interactions were decomposed with simple effects analysis. Hedges' d effect sizes (95%CI) quantified the magnitude of differences in change between groups across time. Stratified analyses were conducted among subsamples with AMDD and AGAD. There were no baseline depressive symptom differences between groups. Attendance was 83%, and compliance was 80%. RET induced statistically significant, clinically-meaningful, large-magnitude reductions in depressive symptoms from baseline to week eight in the total (d = 1.01; [95%CI: 0.44-1.57]), AMDD (d = 1.71; [95%CI: 0.96-2.46]), and AGAD (d = 1.39; [95%CI: 0.55-2.24]) samples. These findings support guidelines-based RET as a promising treatment for mild depression.
Topics: Humans; Female; Young Adult; Depression; Resistance Training; Depressive Disorder, Major; Exercise; Anxiety Disorders
PubMed: 37429171
DOI: 10.1016/j.psychres.2023.115322 -
Nature Neuroscience Aug 2023Major depressive disorder represents a serious public health challenge worldwide; however, the underlying cellular and molecular mechanisms are mostly unknown. Here, we...
Major depressive disorder represents a serious public health challenge worldwide; however, the underlying cellular and molecular mechanisms are mostly unknown. Here, we profile the dorsolateral prefrontal cortex of female cynomolgus macaques with social stress-associated depressive-like behaviors using single-nucleus RNA-sequencing and spatial transcriptomics. We find gene expression changes associated with depressive-like behaviors mostly in microglia, and we report a pro-inflammatory microglia subpopulation enriched in the depressive-like condition. Single-nucleus RNA-sequencing data result in the identification of six enriched gene modules associated with depressive-like behaviors, and these modules are further resolved by spatial transcriptomics. Gene modules associated with huddle and sit alone behaviors are expressed in neurons and oligodendrocytes of the superficial cortical layer, while gene modules associated with locomotion and amicable behaviors are enriched in microglia and astrocytes in mid-to-deep cortical layers. The depressive-like behavior associated microglia subpopulation is enriched in deep cortical layers. In summary, our findings show cell-type and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behaviors in female non-human primates.
Topics: Animals; Humans; Female; Microglia; Depressive Disorder, Major; Transcriptome; RNA; Macaca; Depression
PubMed: 37443281
DOI: 10.1038/s41593-023-01379-4