There is a lack of prospective cohort studies exploring the associations between the timing of physical activity and incident depression. This study aimed to explore the associations and to investigate whether genetic predisposition of depression may modify the associations.

The study using data from UK Biobank, included 76,218 participants. The data of total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) were collected by accelerometer measurements over 7 consecutive days. Cox proportional hazard models were performed to calculate the hazard ratio (HR) and 95 % confidence interval (CI).

In total, compared to the midday-afternoon group, participants in the early morning group of TPA had a lower risk of depression (HR: 0.76, 95 % CI: 0.65-0.89). Compared to the inactive group, a lower risk of incident depression was found among the participants with MVPA in the morning (HR: 0.80, 95 % CI: 0.67-0.96) and middy-afternoon (HR: 0.82, 95 % CI: 0.70-0.96). The joint effect analysis of the timing of TPA and genetic predisposition for incident depression showed that compared to the participants with a high genetic predisposition and in the middy-afternoon group of TPA, early morning group had a reduced risk of depression regardless of genetic predisposition. However, in subgroup analyses for genetic predisposition, only participants with a high genetic predisposition to depression benefited from TPA in the early morning.

TPA in the early morning and MVPA in the morning and middy-afternoon were significantly associated with a lower depression risk, especially for participants with a higher genetic predisposition of depression.

To investigate the associations between accelerometer-measured physical activity and sedentary behavior with depression and anxiety.

We used accelerometer data from the UK biobank. Time spent in moderate-to-vigorous physical activity (MVPA) was classified into four categories: very-low (0-74.9 min/week), low (75-149.9 min/week), moderate (150-299.9 min/week), and high (≥300 min/week). Associations were examined using Cox proportional hazard regression models. Restricted cubic splines were used to evaluate dose-response associations.

A total of 71556 adults (mean [SD] age, 62.11 [7.83] years; 54.5% were female) were included. When stratified by MVPA, 10562 participants were in the very-low group (14.8%), 11578 were in the low group (16.2%), 20700 were in the moderate group (28.9%), and 28716 were in the high group (40.1%). Both MVPA and total physical activity showed nonlinear associations with the risk of depression and anxiety. Compared with very-low level MVPA, moderate MVPA might reduce the risk of depression (HR, 0.71; 95% CI, 0.63-0.79) and anxiety (HR, 0.80; 95% CI, 0.71-0.90). High MVPA was associated with a 30% lower risk of depression (HR, 0.70; 95% CI, 0.62-0.78) and anxiety (HR, 0.70; 95% CI, 0.62-0.79). For sedentary behavior, quartile 4 (≥10.60 h/d) was associated with a 19% higher risk of depression (HR, 1.19; 95% CI, 1.05-1.35) compared to quartile 1 (<8.21 h/d).

The WHO guideline of 150-300 min/week of MVPA may reduce the risk of depression by 29% and anxiety by 20% compared to less than 75 min/week. Prolonged sedentary behavior was associated with a higher risk of depression.

Immune cells and metabolites significantly impact organism health and disease processes. The interaction between non-small cell lung cancer (NSCLC) and metabolites and immune cells remains underexplored.

To investigate the causal relationships between immune cells, metabolites, and NSCLC, we used Mendelian randomization (MR). The research design comprehensively embraced the direct correlation and the role that metabolites play as an intermediate in the interaction between NSCLC and immune cells.

MR analysis allowed us to finally identify one immune cell, there was a substantial causal connection between CD64 on CD14⁻CD16⁻ and NSCLC. Furthermore, we discovered four metabolites that showed strong causal links to NSCLC: 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) levels, phenyllactate (PLA) levels in elite athletes, the caffeine to paraxanthine ratio and 1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6) levels. Finally, through a two-step MR mediation analysis, we found that CD64 on CD14⁻CD16⁻ mediated the occurrence of NSCLC via 1-palmitoleoyl-2-linolenoyl-GPC (16:1/18:3) levels and the caffeine to paraxanthine ratio, with mediation proportions of - 11.89% and 21.69%, respectively.

Our findings show the complicated link between immune cells, metabolites, and NSCLC. The discovered connections and mediating effects provide important insights.

The association between moderate-to-vigorous physical activity (MVPA) with depression are clear but needs to be investigated considering dynamic changes in MVPA. We investigated the association of longitudinal changes in MVPA with depression-related outcomes among depressed and non-depressed participants. From 209,095 depressed and 3,777,173 non-depressed participants of South Korea, MVPA was assessed from health screenings during period 1 (2014-15) and 2 (2016-17) using self-reported questionnaires. Participants were followed up from January 1, 2018 to 1-year and 3-year for any diagnosis of depression. Adjusted odds ratio (aOR) and 95 % confidence interval (CI) were calculated using multivariable-adjusted logistic regression analysis. From depressed participants, consistently highly active participants showed the lowest odds for incident depression (aOR 0.81; 95 % CI 0.70-0.95), while those who increased MVPA showed the lowest odds for depressive symptom (aOR 0.77; 95 % CI 0.72-0.82). When combining MVPA status during period 0 (2012-13) for the longitudinal analysis, the participant with depression at period 1 showed a lower odds if they maintained to be physically active before and after depression diagnosis (from period 0 to period 2). We found epidemiologic evidence that longitudinal evaluation for MVPA from pre-depression state may be important on analyzing depression-related risk.

The present study employed Mendelian randomization to scrutinize the causal connections that may exist between 91 distinct inflammatory markers and six neuropsychiatric disorders, namely Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), anxiety disorders (ANX), depressive disorders (DEP), and unexplained encephalopathy (UE).

The methodology utilized involved the standard inverse variance weighting method within a two-sample, two-way Mendelian randomization framework and integrated statistics from genome-wide association studies. To ascertain the robustness of the identified causal associations, sensitivity analyses were performed with the aid of the MR-Egger method and the weighted median test.

The results revealed that 14 distinct systemic inflammatory modulators are potentially causally linked to the risk of developing various neuropsychiatric disorders. Specifically, five were associated with AD, eight with ANX, six with DEP, and one with UE. However, the causal associations involving systemic inflammatory markers with PD and MS require further investigation, particularly with the identification of additional significant genetic variants. Furthermore, the concentration levels of 33 systemic inflammatory factors could be modulated by the occurrence of neuropsychiatric conditions, indicated by this study. These include five affected by AD, eight by PD, six by MS, 12 by ANX, five by DEP, and five by UE.

Recent studies have underscored a potential link between gut microbiota and urological tumors, yet the causal relationship with bladder cancer (BCa) and the role of metabolic pathways remain unclear.

Instrumental variables (IVs) for gut microbiota were obtained from genome-wide association studies (GWAS) conducted by the MiBioGen consortium (n = 18,340). GWAS data for BCa were sourced from a comprehensive genome-wide meta-analysis encompassing 23 cohorts. Mendelian randomization (MR) was employed to investigate the causal relationship between gut microbiota and BCa, utilizing inverse variance weighted (IVW) as the primary MR method. Additionally, metabolic pathways associated with these microbiota were analyzed to understand their functional roles in BCa pathogenesis. Sensitivity analyses were conducted to validate all MR results.

The MR analysis identified five gut microbiota taxa with a causal association with BCa, with the genus Bilophila notably promoting BCa. Metabolic pathway analysis revealed significant associations between specific pathways and BCa, suggesting that changes in amino acid and NAD metabolism might influence BCa development. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy among the IVs.

This study revealed the significant causal relationship between gut microbiota and BCa, particularly identifying Bilophila as a key pathogenic initiator. These findings elucidated the potential impact of metabolic pathways, especially amino acid and NAD metabolism, on the pathogenesis of BCa. They not only laid the foundation for innovative therapeutic strategies but also highlighted the immense potential of microbiota-based interventions in the prevention and treatment of BCa, paving the way for new directions in precision medicine.

Recent evidence indicates that immune cells are crucial in modulating the pathogenesis of postherpetic neuralgia (PHN), with significant associations identified between immune responses and the development of PHN. However, the specific dynamic immune profile, the underlying molecular mechanisms, and especially the causal relationship between immune cells and PHN have yet to be comprehensively elucidated.

We implemented a comprehensive analytical framework incorporating two-sample Mendelian randomization (MR), multivariable Mendelian randomization(MVMR), and colocalization analyses to elucidate the causal relationships between immune cell phenotypes and PHN. Utilizing publicly available genetic datasets, we explored potential causal associations between 731 immune cell phenotypes and susceptibility to PHN. Comprehensive sensitivity analyses were performed to assess the robustness of the findings, evaluate heterogeneity, and investigate horizontal pleiotropy.The Steiger directionality test was utilized to address and reduce the likelihood of reverse causation.

After applying the Bonferroni-adjusted, eight immune cell phenotypes exhibited significant causal associations with PHN. Further MVMR analysis revealed a significant positive causal relationship between CD27 on IgD- CD38dim B cell and the risk of PHN, with an odds ratio (OR) of 1.228 (95% confidence interval [CI]: 1.059-1.566, P = 0.011). Colocalization analysis offered limited evidence supporting a shared genetic architecture.

Our findings present compelling genetic evidence that identifies CD27 on IgD- CD38dim B cell as a potential therapeutic target for the prevention and treatment of PHN. This study reinforces the mechanistic connection between immune cell function and the pathogenesis of PHN, highlighting the necessity for further exploration in this area. These insights provide significant guidance for future clinical research and the development of therapeutic strategies.

Guidelines recommend 150 min per week (min/wk) or more of moderate to vigorous physical activity (MVPA) for mental health benefits. However, the relative effects of concentrated against more evenly distributed activity patterns remain unclear.

We aimed to examine associations of the accelerometer-derived "weekend warrior (WW)" pattern (MVPA concentrated within 1 to 2 days) vs MVPA spread more evenly with risk of depression and anxiety.

This prospective cohort study included 84,570 participants with accelerometer data identified from the UK Biobank.

Three MVPA patterns were compared: active WW (MVPA ≥150 min/wk and ≥50 % of total MVPA within 1 to 2 days), active regular (MVPA ≥150 min/wk but not active WW), and inactive (MVPA <150 min/wk).

Cox regression was used to assess the association of MVPA patterns with depression and anxiety, and whether the association differed by different levels of sedentary time (≤6, 7-12, ≥13 h/day) and light physical activity (≤60, 61-150, ≥151 min/day). We also evaluated the combined impact of MVPA patterns and genetic susceptibility on depression and anxiety.

During the follow-up of up to 9.40 years, 2098 and 2699 cases of depression and anxiety were identified, respectively. Compared with inactive group, active regular and active WW groups exhibited similarly reduced risks of depression (active regular: HR, 0.74 [95 % CI, 0.66-0.84]; active WW: 0.72 [0.65-0.80]) and anxiety (active regular: 0.77 [0.69-0.86]; active WW: 0.72 [0.66-0.79]). The impact of active regular and active WW groups on depression and anxiety was more pronounced among individuals with excessive sedentary time (≥13 h/day) and insufficient light physical activity (≤60 min/day). Individuals with low genetic risk and active regular (depression: 0.64 [0.48-0.87]; anxiety: 0.62 [0.49-0.79]), as well as low genetic risk and active WW groups (depression: 0.60 [0.47-0.77]; anxiety: 0.59 [0.48-0.72]) exhibited the lowest risks of depression and anxiety compared to those with high genetic risk and inactive group.

Adherence to active physical activity, regardless of physical activity concentrated within 1 to 2 days or more evenly distributed, may help reduce depression and anxiety risks across a population with different genetic risk profiles.

Depression symptoms are commonly experienced by adults and older people; however, there is uncertainty concerning the associations of lifestyle with the risk of depression. This study systematically reviewed and meta-analyzed observational data to assess the link between instrumented sedentary behavior (i-SB) and physical activity (i-PA) measures and depression risk among adult and older populations.

A systematic review across four databases was performed up to July 27, 2024, targeting studies linking i-SB, i-PA, and depression. The review included a dose-response meta-analysis, presenting results as odds ratios (OR) and 95% confidence intervals (95% CI).

Fifty-one studies, encompassing 1,318,687 participants, fulfilled the inclusion criteria. The comparison between the most and least sedentary groups yielded a pooled OR of 1.09 (95% CI 1.05-1.13). The comparison between the least and most active participant groups yielded pooled ORs of 0.96 (95% CI 0.93-0.98) for light activity (LPA), 0.91 (95% CI 0.86-0.96) for moderate-to-vigorous activity (MVPA), 0.93 (95% CI 0.90-0.96) for total physical activity (TPA), and 0.87 (95% CI 0.81-0.94) for steps per day. After adjusting i-PA, a lower OR for i-SB did not indicate a significant link to increased depression risk. Meta-regression analyses confirmed a dose-response relationship between SB, MVPA, daily steps, and depression.

The association between i-SB and the risk of depression was not consistent with the results of previous self-reported studies. MVPA linked to the risk of depression was independent of i-SB, whereas the link between i-SB and the risk of depression was not independent of i-PA.

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=546666, identifier CRD42024546666.

Studies have shown a close correlation among immune cells, plasma metabolites, and atrial fibrillation (AF). However, it is not clear if this association is related, which we used Mendelian randomization (MR) to investigate. We analyzed the association between immune cells, plasma metabolites, and AF by using summarized data from genome-wide association studies. Among them, we explored the associations between immune cells and AF by using bidirectional MR analysis. Combined with mediation analysis and multivariable MR, we further identified potential mediating plasmic metabolites. Results shows that causal relationships between 8 immune cell phenotypes and AF were identified with all 8 exhibiting reverse causality. Furthermore, 22 plasma metabolites have a causal relationship with AF. In addition, 2 immune cell phenotypes including CD25 on IgD + CD38dim and CX3CR1 on CD14 + CD16-monocyte, which were found to have causal relationships with 4 plasma metabolites, including 4-acetamidobutanoate levels, Octadecanedioylcarnitine (C18-DC) levels, Linolenate [alpha or gamma; (18:3n3 or 6)] levels, and N-acetyl-aspartyl-glutamate levels, which might be mediators. Ultimately, only 4-acetamidobutanoate levels, CD25 on IgD + CD38dim, and AF did appear to function as mediators (P-value = .030 < .05). In conclusion, immune cells and plasma metabolites are causally associated with AF. We have identified that 4-acetamidobutanoate levels appear to mediate the pathway linking CD25 on IgD + CD38dim to AF. This finding provides a new perspective for the early prevention and diagnosis of preatrial AF.

Previous observational studies showed associations between obstructive sleep apnea (OSA) and depression and other negative moods. However, the causality has not been determined. Single nucleotide polymorphisms were identified as instrumental variables by screening from genome-wide association studies. Bidirectional two-sample mendelian randomization (MR) was applied to assess the potential causal relationship between OSA and depression, subjective well-being, negative moods. Inverse variance weighting (IVW) method and weight median were chosen as the main methods to estimate possible causal effects. MR-Egger, MR pleiotropy residual sum and outlier and leave-one-out analysis methods, were used as sensitivity analysis methods to ensure robust results. MR analyses indicated significantly causal association of OSA on depression (OR = 1.22, P = .010) and major depressive disorder (OR = 1.02, P = .006). Furthermore, genetically predicted OSA was negatively associated with subjective well-being (βIVW = -0.06, P = .009), and was positively associated with negative moods including depressed affect (OR = 1.04, P = .012), irritable mood (P = .006), feeling lonely (P = .011), feeling fed-up (P = .005) and mood swings (P = .017). There is no reverse effect of the above psychiatric traits on OSA. Genetic predisposition to OSA causally increased depression and major depressive disorder. Consistently, OSA has causal impacts on both subjective well-being, representing positive emotions, and negative moods.

Observational studies and clinical trials have reported potential associations between retinal diseases and psychiatric disorders. However, the causal associations between them have remained elusive. In this study, we used bi-directional two-sample Mendelian randomization (MR) analysis to explore unconfounded causal relationships between retinal diseases and psychiatric disorders using large-scale genome-wide association study (GWAS) summary statistics of over 500,000 participants of European ancestry from the FinnGen project, the Psychiatric Genomics Consortium, the European Bioinformatics Institute, and the UK Biobank. Our MR analysis revealed significant causal relationships between major retinal diseases and specific psychiatric disorders. Specifically, susceptibility to dry age-related macular degeneration was associated with a reduced risk of anorexia nervosa (OR = 0.970; 95% CI = 0.930 ~ 0.994; P = 0.025). Furthermore, we found some evidence that exposure to diabetic retinopathy was associated with an increased risk of schizophrenia (OR = 1.021; 95% CI 1.012 ~ 1.049; P = 0.001), and exposure to retinal detachments and breaks was associated with an increased risk of attention deficit hyperactivity disorder (OR = 1.190; 95% CI 1.063 ~ 1.333; P = 0.003). These causal relationships were not confounded by biases of pleiotropy and reverse causation. Our study highlights the importance of preventing and managing retinal disease as a potential avenue for improving the prevention, management and treatment of major psychiatric disorders.

Physical activity plays a fundamental role in human health and disease. Exercise has been shown to improve a wide variety of disease states, and the scientific community is committed to understanding the precise molecular mechanisms that underlie the exquisite benefits. This review provides an overview of molecular responses to acute exercise and chronic training, particularly energy mobilization and generation, structural adaptation, inflammation, and immune regulation. Furthermore, it offers a detailed discussion of known molecular signals and systemic regulators activated during various forms of exercise and their role in orchestrating health benefits. Critically, the increasing use of multiomic technologies is explored with an emphasis on how multiomic and multitissue studies contribute to a more profound understanding of exercise biology. These data inform anticipated future advancement in the field and highlight the prospect of integrating exercise with pharmacology for personalized disease prevention and treatment.

The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined.

To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP.

A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP.

Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained.

With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

Being physically inactive can worsen mental health. Physical inactivity and depression are associated, but the temporal precedence and underlying mechanism are unclear; symptoms affecting future physical activity may not be the same symptoms as those associated with and affected by it. We used large European cohort (Survey of Health, Ageing, and Retirement in Europe, SHARE, N = 124, 526) to study temporal associations between physical inactivity and individual depressive symptoms. Multivariate regression with robust standard errors were used to analyze how physical inactivity is associated with later depression and how depressive symptoms predict later physical inactivity. After adjusting the models for demographics, other health behaviors, BMI, and chronic diseases, physical inactivity was prospectively associated with 10 of the 12 depressive symptoms and 7 of the 12 baseline depressive symptoms were prospectively associated with physical inactivity. These findings were robust for adjusting for antidepressant medication. Age-stratified analyses suggested that the associations between physical inactivity and depressive symptoms were independent of age. Omitting the most influential symptom, lack of enjoyment, from the sum score attenuated the association by 13% in the longitudinal and by 26% in the cross-sectional analyses. These findings suggest that physical inactivity and depression are bidirectionally associated even at symptom-level.

To examine the combined association of physical inactivity and depressive symptoms with the progression to sarcopenia in community-dwelling older adults.

A 4-year follow-up longitudinal study.

Community-dwelling older adults living in Japan, who were not sarcopenic at baseline.

The participants were 2,538 community-dwelling older adults and with a mean age of 70.9 ± 4.6 years, of whom 1,327 (52.3%) were women.

Sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2, was assessed at baseline and at the 4-year follow-up. Participants were divided into four groups according to their inactivity and depressive symptoms. Physical inactivity was assessed using two face-to-face questions regarding the frequency of regular exercise, sports, and light exercise per week. Depressive symptoms were defined as a score of six or higher on the Geriatric Depression Scale 15-item version. Logistic regression analysis was used to determine whether inactivity and depressive symptoms were associated with progression to sarcopenia 4 years later. For participants who could not be followed and participants with missing data in the follow-up assessment, the data at the follow-up assessment were imputed using the multiple imputations.

After 4 years, 518 participants (20.4%) with complete data progressed to sarcopenia. The rate of progression to sarcopenia after multiple imputations was 23.4%. Logistic regression analysis after multiple imputations showed that the group with both factors was significantly associated with the progression to sarcopenia [Odds ratio, 1.64 (95% Confidence interval 1.11-2.44), p = 0.014]. By contrast, no significant association was found for either inactivity or depressive symptoms alone.

This study indicates that the coexistence of physical inactivity and depressive symptoms may contribute to the progression of sarcopenia. Addressing both physical and mental factors, rather than limiting the problem to a single factor, may be essential for preventing sarcopenia.

Childhood maltreatment is increasingly recognized as a pivotal risk factor for adverse health outcomes. However, comprehensive analyses of its long-term impact are scarce. This study aims to fill this gap by examining the genetic architectures of childhood maltreatment and its influence on adult health and socioeconomic outcomes. Utilizing data from the UK Biobank (N = 129,017), we conducted sex-combined and sex-stratified genome-wide association studies to identify genomic loci associated with five childhood maltreatment subtypes. We then performed genetic correlation and Mendelian randomization (MR) analyses to assess the effects of childhood maltreatment on high-burden diseases, healthcare costs, lifespan, and educational attainment. We identified several novel loci for childhood maltreatment, including one locus for sexual abuse in sex-combined analysis, one novel locus for sexual abuse in males, one locus for emotional neglect in females, and one locus for sexual abuse in females. The pairwise genetic correlations between subtypes of childhood maltreatment were moderate to high, and similar patterns of genetic correlations between childhood maltreatment subtypes were observed in males and females. Childhood maltreatment was genetically correlated with ten out of 16 high-burden diseases significantly after multiple testing correction. Moreover, MR analyses suggest childhood maltreatment may increase the risk of age-related and other hearing loss, low back pain, major depressive disorder, and migraine in adulthood, and reduce the lifespan. Our study elucidates the genetic architecture of specific childhood maltreatment subtypes and the influence of childhood maltreatment on health outcomes in adulthood, highlighting the enduring influence of childhood maltreatment on lifelong health consequences. It is important to develop prevention strategies to lower the incidence of childhood maltreatment and provide support and care for victims of childhood maltreatment for better long-term health outcomes in the population.

To investigate the mediating effect of life satisfaction between physical exercise behavior and depressive symptoms among middle-aged and elderly individuals, providing a reference for improving depressive conditions in this demographic group.

Data from 11,101 middle-aged and elderly individuals from the 2020 China Family Panel Studies (CFPS) were collected. STATA 17.0 was used for data cleaning, organization, and statistical analysis which includes univariate analysis, stepwise regression analysis, and mediation effect testing.

Among 11,101 individuals aged 45 years and above, 2,272 participated in physical exercise, accounting for 20.47%; 2,052 exhibited depressive symptoms, representing 18.48%. Physical exercise was positively correlated with life satisfaction and negatively correlated with depression. Depression scores also showed a negative correlation with life satisfaction. According to the results of the mediation effect study, life satisfaction accounted for 16.60% of the overall effect and had a mediating effect value of -0.099 on depression symptoms.

Physical exercise and life satisfaction are factors influencing depressive symptoms, and life satisfaction acts as a partial mediator between physical exercise participation and depression among middle-aged and elderly adults.

Previous studies (various designs) present contradicting insights on the potential causal effects of diet/physical activity on depression/anxiety (and vice versa). To clarify this, we employed a triangulation framework including three methods with unique strengths/limitations/potential biases to examine possible bidirectional causal effects of diet/physical activity on depression/anxiety.

Study 1: 3-wave longitudinal study (n = 9,276 Dutch University students). Using random intercept cross-lagged panel models to study temporal associations. Study 2: cross-sectional study (n = 341 monozygotic and n = 415 dizygotic Australian adult twin pairs). Using a co-twin control design to separate genetic/environmental confounding. Study 3: Mendelian randomization utilizing data (European ancestry) from genome-wide association studies (n varied between 17,310 and 447,401). Using genetic variants as instrumental variables to study causal inference.

Study 1 did not provide support for bidirectional causal effects between diet/physical activity and symptoms of depression/anxiety. Study 2 did provide support for causal effects between fruit/vegetable intake and symptoms of depression/anxiety, mixed support for causal effects between physical activity and symptoms of depression/anxiety, and no support for causal effects between sweet/savoury snack intake and symptoms of depression/anxiety. Study 3 provides support for a causal effect from increased fruit intake to the increased likelihood of anxiety. No support was found for other pathways. Adjusting the analyses including diet for physical activity (and vice versa) did not change the conclusions in any study.

Triangulating the evidence across the studies did not provide compelling support for causal effects of diet/physical activity on depression/anxiety or vice versa.

Little is known about the dose and pattern of moderate-to-vigorous physical activity (MVPA) to prevent depression. We aimed to assess the prospective association of dose and pattern of accelerometer-derived MVPA with the risk of diagnosed depression.

We included 74,715 adults aged 40-69 years from the UK Biobank cohort who were free of severe disease at baseline and participated in accelerometer measurements (mean age 55.2 years [SD 7.8]; 58% women). MVPA at baseline was derived through 1-week wrist-worn accelerometry. Diagnosed depression was defined by hospitalization with ICD-10 codes F32.0-F32.A. Restricted cubic splines and Cox regression determined the prospective association of dose and pattern of MVPA with the risk of incident depression.

Over a median 7.9-year follow-up, there were 3,089 (4.1%) incident cases of depression. Higher doses of MVPA were curvilinearly associated with lower depression risk, with the largest minute-per-minute added benefits occurring between 5 (HR 0.99 [95% CI 0.96-0.99]) and 280 (HR 0.67 [95% CI 0.60-0.74]) minutes per week (reference: 0 MVPA minutes).

Regardless of pattern, higher doses of MVPA were associated with lower depression risk in a curvilinear manner, with the greatest incremental benefit per minute occurring during the first 4-5 h per week. Optimal benefits occurred around 15 h/week.

Today's fitness bands and smartwatches typically track heart rates (HR) using optical sensors. Large behavioral studies such as the U.K. Biobank use activity trackers without such optical sensors and thus lack HR data, which could reveal valuable health trends for the wider population. In this paper, we present the first dataset of wrist-worn accelerometer recordings and electrocardiogram references in uncontrolled at-home settings to investigate the recent promise of IMU-only HR estimation via ballistocardiograms. Our recordings are from 42 patients during the night, totaling 310 hours. We also introduce a frequency-based method to extract HR via curve tracing from IMU recordings while rejecting motion artifacts. Using our dataset, we analyze existing baselines and show that our method achieves a mean absolute error of 0.88 bpm-76% better than previous approaches and the first to surpass established medical standards for heart rate monitors. Our results validate the potential of IMU-only HR estimation as a key indicator of cardiac activity in existing longitudinal studies to discover novel health insights.

Recent studies suggest immunophenotypes may play a role in asthma, but their causal relationship has not been thoroughly examined.

We used single nucleotide polymorphism (SNP)-derived instrumental variables. Summary data from 731 immune cell profiles and asthma cases were analyzed from genome-wide association studies (GWAS) of European populations. Mendelian Randomization (MR) analyses included inverse variance weighted (IVW), weighted median, and MR-Egger methods. Pleiotropy was assessed using the MR-Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Reverse MR analysis explored bidirectional causation between asthma and immunophenotypes. All statistical analyses were conducted using R software.

MR analysis identified 108 immune signatures potentially contributing to asthma. Two immunophenotypes were significantly associated with asthma risk: CD4+ secreting Treg cells in allergic asthma (ORIVW = 1.078; 95% CI: 1.036-1.122; PIVW = 0.0002) and IgD + CD38- %lymphocyte cells in non-allergic asthma (ORIVW = 1.123; 95% CI: 1.057-1.194; PIVW = 0.0002).

This study highlights the causal associations between specific immunophenotypes and asthma risk, providing new insights into asthma pathogenesis.

Depression and cardiovascular health (CVH) are interconnected, and both are independently associated with mortality. However, the joint effects of depressive symptoms and CVH on mortality remain unclear.

By utilizing the National Health and Nutrition Examination Survey (NHANES) 2007-2018, we included 18,679 adults aged ≥20 years without cardiovascular diseases (CVD). The definition of elevated depressive symptoms was based on the Patient Health Questionnaire-9 (PHQ-9) scores≥10. CVH was evaluated by Life's Essential 8 (LE8) and categorized into low (<50), moderate (50-80), or high (≥80). The joint association of depressive symptoms and CVH with mortality was examined utilizing multivariate Cox proportional hazard models.

Elevated depressive symptoms were associated with higher mortality risks, and CVH could explain 12.7 % and 13.7 % of the associations between depression and all-cause and non-CVD mortality, respectively. No significant interactions were found between CVH and depressive symptoms on mortality. High CVH attenuated the all-cause mortality risk in patients with elevated depressive symptoms (HR, 0.20; 95 % CI: 0.05-0.89). Compared to participants with elevated depressive symptoms and low CVH, those with no elevated depressive symptoms and high CVH had lower risks of all-cause (HR, 0.26; 95 % CI: 0.16-0.43), CVD (HR, 0.20; 95 % CI: 0.07-0.52), non-CVD mortality (HR, 0.28; 95 % CI 0.16-0.50).

Adults with low CVH and elevated depressive symptoms had significantly higher risks of all-cause, CVD, and non-CVD mortality. The finding suggests considering depressive symptoms and CVH jointly in developing targeted strategies to improve survival.

Previous studies have indicated that, in addition to the types of food consumed, eating habits are also associated with the risk of esophageal diseases. Some studies have suggested a possible link between breakfast skipping and esophageal tumors as well as gastroesophageal reflux disease. However, it remains unclear whether breakfast skipping has a causal relationship with esophageal diseases. To address this issue, this study aimed to investigate the potential causal relationship between breakfast skipping and esophageal diseases using a two-sample mendelian randomization (MR) approach.

We obtained data from genome-wide association studies (GWAS) involving 193,860 individuals from the UK Biobank on breakfast skipping. The summary statistics for the esophageal diseases were derived from the IEU open GWAS project. In this two-sample MR analysis, inverse variance weighted was used, supplemented with weighted median, simple mode and weighted mode methods.

The results revealed significant causal relationships between breakfast skipping and esophageal cancer (odds ratio (OR): 5.992, 95 % confidence interval (CI): 1.606-22.350, p = 0.008), Barrett's esophagus (OR: 4.041, 95 % CI: 1.837-8.889, p < 0.001), gastroesophageal reflux disease (OR: 2.463, 95 % CI: 1.995-3.041, p < 0.001), and esophageal varices (OR: 4.454, 95 % CI: 1.785-11.112, p = 0.001). All of the supplementary methods supported the findings.

Our research provides evidence for the association between breakfast skipping and esophageal diseases. Breakfast skipping could be a potential risk factor for esophageal cancer, Barrett's esophagus, gastroesophageal reflux disease and esophageal varices. For high-risk groups prone to these esophageal diseases, emphasizing the importance of regular breakfast and maintaining consistent dietary habits is crucial for esophageal health.

Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs) have been observed to have a potential association, with GBS potentially leading to cardiovascular complications. However, these observational studies may be influenced by confounding factors. This study aimed to assess the causal relationship between GBS and CVDs, including heart failure (HF), atrial fibrillation (AF), and coronary artery disease (CAD), using a two-sample bidirectional Mendelian randomization (MR) analysis. We analyzed four datasets from the UK Biobank, selecting only datasets of European origin according to predetermined criteria to avoid population stratification bias. Datasets for GBS and CVDs were retrieved from the UK Biobank and analyzed using selected instrumental variables (IVs) related to genetic variations. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the reliability of the selected IVs. The analysis results were then visualized to illustrate the causal relationships. The study identified genetic variants as IVs for both GBS and CVDs. MR analysis revealed a significant causal effect of GBS on the increased risk of HF [inverse-variance weighted (IVW), P < 0.05], but no significant causal relationship was found between GBS and AF or CAD. Similarly, no causal effect of CVDs on the occurrence of GBS was observed. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the results. These findings underscore the importance of considering cardiovascular complications, particularly HF, in the clinical management of patients with GBS in European populations.NEW & NOTEWORTHY This study utilizes bidirectional Mendelian randomization to analyze the causal relationships between Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs). It uniquely demonstrates a significant causal link from GBS to an increased risk of heart failure (HF), without similar effects on atrial fibrillation (AF) or coronary artery disease (CAD). No reverse causality from CVDs to GBS was found, highlighting the need for targeted cardiovascular management in patients with GBS.

Physical activities are widely implemented for non-pharmacological intervention to alleviate depressive symptoms. However, there is little evidence supporting their genotype-specific effectiveness in reducing the risk of self-harm in patients with depression.

To assess the associations between physical activity and self-harm behaviour and determine the recommended level of physical activity across the genotypes.

We developed the bidirectional analytical model to investigate the genotype-specific effectiveness on UK Biobank. After the genetic stratification of the depression phenotype cohort using hierarchical clustering, multivariable logistic regression models and Cox proportional hazards models were built to investigate the associations between physical activity and the risk of self-harm behaviour.

A total of 28 923 subjects with depression phenotypes were included in the study. In retrospective cohort analysis, the moderate and highly active groups were at lower risk of self-harm behaviour. In the followed prospective cohort analysis, light-intensity physical activity was associated with a lower risk of hospitalisations due to self-harm behaviour in one genetic cluster (adjusted hazard ratio, 0.28 [95% CI, 0.08-0.96]), which was distinguished by three genetic variants: rs1432639, rs4543289 and rs11209948. Compliance with the guideline-level moderate-to-vigorous physical activities was not significantly related to the risk of self-harm behaviour.

A genotype-specific dose of light-intensity physical activity reduces the risk of self-harm by around a fourth in depressive patients.

Breast cancer is a significant traumatic experience that often leads to chronic stress and mental health challenges. Research has consistently shown that physical activity-especially exercise-can alleviate depressive symptoms; however, the specific biological mechanisms underlying these antidepressant effects remain unclear. In this review, we comprehensively summarize the biological mechanisms of depression and the antidepressant mechanisms of physical activity and explore the biological processes through which exercise exerts its antidepressant effects in breast cancer patients. We focus on the impact of physical activity on inflammation, the endocrine system, glutamate, and other aspects, all of which play crucial roles in the pathophysiology of depression. Moreover, we discuss the heterogeneity of depression in breast cancer patients and the complex interactions between its underlying mechanisms. Additionally, we propose that a deeper understanding of these mechanisms in the breast cancer population can guide the design and implementation of exercise-based interventions that maximize the antidepressant benefits of physical activity. Finally, we summarize the current research and propose future research directions.

To investigate the associations between device-measured and self-reported physical activity (PA) and incident common mental disorders in the general population.

Large-scale prospective cohort study.

Using the UK Biobank data, a validated PA questionnaire was used to estimate self-reported weekly PA in 365 656 participants between 2006 and 2010 while 91 800 participants wore wrist-worn accelerometers for 7 days in 2013-2015 to derive objectively measured PA. All the participants were followed up until 2021.

Incidences of depression and anxiety were ascertained from hospital inpatient records. Cox proportional hazards models and restricted cubic splines were used to assess the associations between subjectively and objectively measured PA and common mental disorders.

During a median follow-up of 12.6 years, 16 589 cases of depression, 13 905 cases of anxiety and 5408 cases of comorbid depression and anxiety were documented in the questionnaire-based cohort. We found J-shaped associations of self-reported PA with incident risk of depression and anxiety, irrespective of PA intensities. The lowest risk for depression occurred at 550, 390, 180 and 560 min/week of light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA) and moderate-to-vigorous PA (MVPA), respectively. During a median follow-up of 6.9 years, a total of 2258 cases of depression, 2166 cases of anxiety and 729 cases of comorbid depression and anxiety were documented in the accelerometer-based cohort. We found L-shaped associations of device-measured MPA and VPA with incident depression and anxiety. MPA was adversely associated with incident depression and anxiety until 660 min/week, after which the associations plateaued. The point of inflection for VPA occurred at 50 min/week, beyond which there was a diminished but continued reduction in the risks of depression and anxiety.

Different patterns of associations between self-reported and device-measured PA and mental health were observed. Future PA guidelines should fully recognise this inconsistency and increasingly employ objectively measured PA standards.

Regular participation in physical activity (PA) reduces all-cause mortality (ACM) in the general population. However, the effects of PA on depressed patients and potential gender-specific responses have not been fully elucidated. In this study, we aimed to investigate the role of PA on new-onset depression and ACM in Chinese adults aged 45 year and older, with particular emphasis on gender differences.

This was a longitudinal cohort study that took place over a nine-year period and featured 2,264 participants drawn from the China Health and Retirement Longitudinal Study (CHARLS). PA levels were categorized into quartiles using metabolic equivalents (MET; minutes/week), and depression was evaluated according to the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) scale. Specific relationships between PA, depression, and mortality were then investigated by applying multivariate logistic regression and Cox proportional hazards models.

Highest quantile levels of PA were correlated with a 37% increase in the risk of new-onset depression in middle-aged (45-59 years) and older adults (>60 years). This association was predominantly influenced by a significant increase in the risk of mild depression (a score of 10-14 on the CESD-10) (odds ratio [OR]: 1.76; 95% confidence interval [CI]: 1.29-2.42, p < 0.001), with a more pronounced effect observed in women (OR: 1.83; 95% CI: 1.26-2.66, p = 0.002). A critical threshold for PA was identified at 4536 MET-minutes/week, beyond which the risk of depression increased significantly (p < 0.05). Conversely, higher levels of PA were linked to a 90% reduction in ACM (HR: 0.10; 95% CI: 0.02-0.44, p = 0.002), with the effect being more pronounced in men.

While PA reduces mortality, excessive activity may increase the risk of mild depression, particularly in women. These findings highlight the need for gender-specific PA guidelines that balance physical and mental health outcomes.

Abdominal aortic aneurysm (AAA) is one of the most dangerous types of vascular diseases worldwide. Metabolic disturbance affects disease risk and provide underlying therapeutic targets. Previous studies have reported an association between metabolic disorders and AAA. However, evidence of a causal relationship between blood metabolites and AAA is still lacking at present.

Using Mendelian randomization (MR), we assessed the causal association between 1,400 serum metabolites and AAA. The inverse variance weighted method (IVW), weighted median, MR-Egger regression, simple mode, as well as weighted mode methods were used for evaluating the causality between blood metabolites and AAA. Pleiotropy and heterogeneity tests were further conducted.

Through strict screening, 17 known metabolites, 7 unknown metabolites and 5 metabolite ratios related to AAA were identified. Among all the metabolites, 24 were found to have negative associations, while 5 exhibited positive associations. The top five metabolites associated with an increased risk of AAA were Oleoyl-linoleoyl-glycerol (18:1/18:2) [2], Glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1(2OH)), Glycochenodeoxycholate 3-sulfate, X-21441 and X-24328. In contrast, the top five metabolites that were linked to a reduced risk of AAA included Uridine to pseudouridine ratio, Octadecanedioate, Phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] ratio, 1-(1-enyl-palmitoyl)-GPE (p-16:0), and 1-stearoyl-GPG (18:0).

Among the 1,400 blood metabolites, we identified 17 known metabolites, 7 unknown metabolites, and 5 metabolite ratios associated with AAA. This MR study may provide a novel significant insight for the screening and prevention of AAA.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), decreases quality of life and causes disability. The underlying processes are not fully understood. This study uses Mendelian randomization (MR) analysis to identify cytokines that may be associated with UC and CD, aiding in early diagnosis and treatment decisions. Methods Genome-wide association study (GWAS) data for inflammatory cytokine levels were obtained from a cohort of 14,824 individuals of European descent. The outcome data were then analyzed using summary-level GWAS data for UC and CD from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The analysis was primarily conducted using inverse-variance weighted (IVW) methods, with MR-Egger and weighted median serving as supplementary analyses. Sensitivity analyses included Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis.The inflammatory cytokines were subjected to additional scrutiny through the application of the Steiger test and reverse Mendelian randomization analysis. Subsequently, multivariable Mendelian randomization (MVMR) was employed to examine the associations of metabolites on UC and CD, in conjunction with linkage disequilibrium score regression (LDSC) and colocalization analysis. After FDR correction, we identified significant genetic associations of two inflammatory proteins (CXCL5 and CXCL9) with UC, and CXCL5 and IL-18R1 with CD. These findings were further validated by MVMR. Colocalization analyses demonstrated substantial genetic overlap between inflammatory proteins and IBD, with CXCL5 showing strong evidence of shared genetic variants with UC, and CXCL9 exhibiting genetic colocalization with CD, suggesting common genetic determinants underlying these inflammatory protein-IBD relationships. The current work presents evidence that presents evidence of significant associations between seven inflammatory protein factors and UC, as well as three inflammatory protein factors and CD. These findings provide novel insights into the biological mechanisms of IBD, and have implications for the screening, prevention, and treatment of IBD.

The network theory posits that depression emerges as the result of individual symptoms triggering each other. Risk factors for depression can impact these between-symptoms interactions through extended networks. The study aimed to model the extended network of depressive symptoms and known depression risk factors - objective cognitive function, intellectual, physical, and social daily activities, and then, compare the observed networks between monozygotic (MZ) and dizygotic (DZ) co-twins.

Twin pairs, 722 MZ and 2200 DZ, aged 40-79, were selected from the Dansh Twin Registry for having complete measures of depressive symptoms (e.g., sadness), cognitive functions (e.g., verbal memory), physical (e.g., brisk walk), intellectual (e.g., reading newspapers) and social activities (e.g., phone calls). Gaussian graphical models were used to estimate and compare the networks first between co-twins and then, between MZ to DZ twin pairs separately.

Specific intellectual, physical and social activities were central in the extended networks of depressive symptoms and, with the exception of processing speed, more central than cognition. The extended networks' structure was more homogeneous between MZ co-twins relative to DZ co-twins. Cognitive nodes were more central in MZ than DZ co-twins.

Cross-sectional design, participants were middle-aged or older, mostly affective (non-somatic) depressive symptoms.

In depression networks, core connecting elements were intellectual, physical and social activities. The interaction between cognition and daily activities seems critical for triggering depressive symptoms. Thus, clinical interventions aimed at preventing depression and associated cognitive deficits should focus on maintenance and/or engagement in stimulating daily activities.

The role of immune cells in type 1 diabetes (T1D) is unclear. The aim of this study was to assess the causal effect of different immune cells on T1D using Mendelian randomization (MR).

A dataset of immune cell phenotypes (numbered from GCST0001391 to GCST0002121) was obtained from the European Bioinformatics Institute, while a T1D dataset (numbered finngen_R10_T1D) was obtained from FinnGen. Single nucleotide polymorphisms meeting the conditions were screened stepwise according to the assumptions of association, independence, and exclusivity. Inverse variance weighted was used as the main method for the MR analysis. MR-Egger was used to assess the horizontal pleiotropy of the results. Cochran's Q and the leave-one-out method were respectively used for the heterogeneity analysis and the sensitivity analysis of the results.

MR analysis showed that effector memory (EM) double-negative (DN) (CD4-CD8-) %T cells [odds ratio (OR) = 1.157, 95% confidence interval (95% CI) = 1.016-1.318, p = 0.028, false discovery rate (FDR) = 0.899], EM CD8br %T cells (OR = 1.049, 95% CI = 1.003-1.098, p = 0.037, FDR = 0.902), CD28 on CD28+CD45RA+CD8br (OR = 1.334, 95% CI = 1.132-1.571, p = 0.001, FDR = 0.044), IgD+CD38dim %lymphocytes (OR = 1.045, 95% CI = 1.002-1.089, p = 0.039, FDR = 0.902), CD80 on monocytes (OR = 1.084, 95% CI = 1.013-1.161, p = 0.020, FDR = 0.834), SSC-A on plasmacytoid dendritic cells (pDCs) (OR = 1.174, 95% CI = 1.004-1.372, p = 0.044, FDR = 0.902), and FSC-A on pDCs (OR = 1.182, 95% CI = 1.011-1.382, p = 0.036, FDR = 0.902) were associated with an increased genetic susceptibility to T1D. Cochran's Q showed that there was heterogeneity for CD28 on the CD28+CD45RA+CD8br results (p = 0.043), whereas there was no heterogeneity for the other results (p ≥ 0.05). The sensitivity analysis showed that the MR analysis results were robust.

The MR analysis demonstrated that seven immune cell phenotypes were associated with an increased genetic susceptibility to T1D. These findings provide a new direction for the pathogenesis of and the drug development for T1D.

Previous clinical studies have suggested an increased risk of tumor development in patients with pulmonary arterial hypertension (PAH). However, it remains unclear whether there is a causal relationship between PAH and tumor occurrence. This study investigates the causal link between PAH and cancer from a genetic perspective using Mendelian randomization (MR).

Genome-wide association study (GWAS) summary data for PAH and various common cancer types were obtained from the GWAS Catalog. Single nucleotide polymorphisms (SNPs) significantly associated with PAH at the genome-wide significance threshold (P < 1 × 10-6) were selected as instrumental variables (IVs). Inverse-variance weighted (IVW) was used as the primary method for MR analysis, with sensitivity analyses including tests for heterogeneity and horizontal pleiotropy.

The results from the IVW analysis indicate that genetically proxied PAH is associated with an increased risk of liver cancer [odd ratio (OR) 1.11, 95% confidence interval (CI) 1.01-1.22, P = 0.025), while showing no significant causal relationship with other common types of tumors (thyroid cancer: OR 0.95, 95% CI 0.86-1.06, P = 0.360; lung cancer: OR 0.95, 95% CI 0.90-1.01, P = 0.129; gastric cancer: OR 0.97, 95% CI 0.93-1.02, P = 0.243; colorectal cancer: OR 1.01, 95% CI 0.98-1.05, P = 0.412). Except for the MR analysis examining the causal effect of PAH on lung cancer (P = 0.049), the remaining MR analyses displayed no significant heterogeneity (P > 0.05). Additionally, the MR-Egger intercept test did not find evidence of horizontal pleiotropy (P > 0.05).

This study highlights that PAH may serve as a potential risk factor for this liver cancer. Future research should aim to elucidate the biological mechanisms at play and explore the potential for early interventions that could mitigate cancer risk in this vulnerable population.

Previous studies reported the effect of physical activity (PA) or sedentary behavior (SB) on increasing occurrence of depression in patients with cardiovascular disease, leading to a higher risk of adverse clinical outcomes. However, the association between the combination of PA and SB and depression in patients with cardiovascular disease remained unstudied.

Patients with cardiovascular disease (aged ≥18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Multivariable logistic regression was used to investigate the association between PA, SB, and depression.

Among the 2585 patients (mean age 64.43 years; 54.65 % male) in this study, the prevalence of depression was 16.40 %. After adjustment for age, gender, race, education level, marital status, poverty income ratio, employment status, smoking, alcohol use, BMI, hypertension, and number of cardiovascular diseases, depression was negatively associated with higher PA (adjusted OR = 0.567, 95 % CI 0.403, 0.799) and positively associated with higher SB (adjusted OR = 1.472, 95 % CI 1.089, 1.990), respectively. The risk of depression associated with higher PA and lower SB was significantly lower (adjusted OR = 0.464, 95 % CI 0.307, 0.702) compared to those with lower PA but higher SB.

This was a cross-sectional study with limited ability to make causal inferences.

Our findings indicate that patients with higher PA and lower SB have a lower risk of depression than those with low PA levels and high SB levels. Moving more and sitting less is a potential preventive measure against depression in patients with cardiovascular disease.

Depression is a major public health problem worldwide and is closely related with systemic inflammatory responses. Additionly, physical activity (PA) is thought to be associated with lower levels of depression and inflammatory markers. This study aimed to elucidate the complex interactions between PA, depression, and inflammatory markers. Based on the National Health and Nutrition Examination Survey (NHANES), various logistic regression were applied to analyze the pairwise correlations among the three. Restrictive cubic splines were constructed to explore the nonlinear relationship between PA and depression. Mediation models were used to identify the mediating role of inflammatory markers. The findings revealed a positive link between depression and inflammatory marker, whereas PA was inversely correlated with both inflammatory marker and depression. Particularly, we noticed the greatest reduction in the risk of depression when the level of PA was between 1200 and 1722 MET-min/week. Besides, we demonstrated that inflammatory markers mediate the potential effects of physical inactivity on depression, ranging from 1.72 % to 6.25 %. In conclusion, PA appear to protect against depression, in which inflammatory markers may play a mediating role. Moreover, we determined the optimal dosage of PA to minimize the likelihood of depression, thereby offering valuable guidance for managing depression.

The relationship between hyponatremia and osteoporosis is controversial, and it remains unclear if there is a causal link between the two. This study employed a 2-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between hyponatremia and osteoporosis. The instrumental variables were derived from genome-wide association studies conducted in European populations. These included hyponatremia (n = 465,348) as the exposure factor, with genetic summary data for bone mineral density (BMD) at the forearm (n = 8134), femoral neck (n = 32,735), lumbar spine (n = 28,498), and heel (n = 265,627) as outcomes. The inverse variance weighted method did not identify any causal effect of hyponatremia on BMD. Additionally, other methods, such as MR-Egger, weighted median, simple mode, and weighted mode, also did not show evidence of a causal relationship between hyponatremia and BMD. Pleiotropy and heterogeneity analyses indicated that the MR findings were robust. There is no significant causal relationship between hyponatremia and osteoporosis. The previously observed associations may be due to confounding factors. It is unlikely that hyponatremia is a causal factor for osteoporosis.

We investigated the relationship between systematic regulators of inflammation and the risk of age-related macular degeneration (AMD), both wet and dry forms, by using bidirectional, two-sample Mendelian randomization (MR).

We performed bidirectional two-sample Mendelian randomization analysis using genome-wide study (GWAS) data for 91 plasma proteins from 14,824 individuals of European descent across 11 study groups. Next, we utilized data from the FinnGen consortium to study AMD using the inverse- variance-weighted approach for Mendelian randomization. Additional analyses involved MR-Egger, Weighted median, Weighted mode, MR-PRESSO, and MR- Steiger filtering techniques.

We identified 16 cytokines associated AMD outcomes and post FDR correction, higher levels of fibroblast growth factor 19 and leukemia inhibitory factor receptor were associated with decreased risk for AMD, while higher levels of tumour necrosis factor ligand superfamily member 14 were associated with increased risk for AMD. Additionally, higher levels of interleukin-10 receptor subunit alpha were associated with decreased risk for wet AMD, higher levels of leukemia inhibitory factor receptor were associated with decreased risk for dry AMD, and higher levels of signaling lymphocytic activation molecule were associated with increased risk for dry AMD. Genetic susceptibility to AMD was associated with elevated levels of TNF-related activation-induced cytokines (TNFSF11), and genetic susceptibility to wet AMD was associated with elevated levels of TNFSF11, interleukin-18 receptor 1 (IL18R1), and CUB domain-containing protein 1 (CDCP1).

This research enhances our understanding of systemic inflammation in AMD, providing insights into etiology, diagnosis, and treatment of AMD and its forms.

The relationship between migraine and Parkinson's disease (PD) remains controversial. We aimed to investigate the causal and genetic associations between migraine and PD.

Genetic data for migraine [any migraine (AM), migraine without aura (MO), and migraine with aura (MA)] and PD were sourced from the latest genome-wide meta-analyses conducted by the International Headache Genetics Consortium and the International Parkinson's Disease Genomics Consortium, respectively. Various analyses were performed to evaluate the potential causal associations and explore genetic correlations between these conditions.

The analyses indicated that AM (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.91-1.14; p = 0.785), MO (OR 0.94, 95% CI 0.84-1.07; p = 0.358), and MA (OR 1.01, 95% CI 0.95-1.06; p = 0.846) were not significantly associated with the risk of PD. Similarly, reverse analyses also demonstrated no significant causality between PD and the risks of migraine or its subtypes. After adjusting for coronary heart disease, AM (OR 0.99, 95% CI 0.90-1.10; p = 0.897), MO (OR 0.94, 95% CI 0.86-1.03; p = 0.207), and MA (OR 1.00, 95% CI 0.93-1.07; p = 0.902) remained unrelated to PD risk. Likewise, PD was found to be unassociated with AM (OR 0.96, 95% CI 0.92-1.02; p = 0.168), MO (OR 0.95, 95% CI 0.86-1.05; p = 0.287), and MA (OR 1.02, 95% CI 0.93-1.13; p = 0.669). These null findings persisted even when adjusting for hypertension. Apart from above causal inference results, no significant genetic correlation was found between AM (rg = -0.06, p = 0.127), MA (rg = -0.05, p = 0.516), or MO (rg = -0.06, p = 0.492) and PD, and no correlations were observed across specific genomic regions. Additionally, no shared heritability was observed between PD and migraine, or its subtypes, in tissue expression.

Our study suggests that there is no significant causal association or genetic correlation between migraine and PD from a genetic perspective.

There is growing interest in lifestyle interventions as stand-alone and add-on therapies in mental health care due to their potential benefits for both physical and mental health outcomes. We evaluated lifestyle interventions focusing on physical activity, diet, and sleep in adults with severe mental illness (SMI) and the evidence for their effectiveness. To this end, we conducted a meta-review and searched major electronic databases for articles published prior to 09/2022 and updated our search in 03/2024. We identified 89 relevant systematic reviews and assessed their quality using the SIGN checklist. Based on the findings of our meta-review and on clinical expertise of the authors, we formulated seven recommendations. In brief, evidence supports the application of lifestyle interventions that combine behavioural change techniques, dietary modification, and physical activity to reduce weight and improve cardiovascular health parameters in adults with SMI. Furthermore, physical activity should be used as an adjunct treatment to improve mental health in adults with SMI, including psychotic symptoms and cognition in adults with schizophrenia or depressive symptoms in adults with major depression. To ameliorate sleep quality, cognitive behavioural informed interventions can be considered. Additionally, we provide an overview of key gaps in the current literature. Future studies should integrate both mental and physical health outcomes to reflect the multi-faceted benefits of lifestyle interventions. Moreover, our meta-review highlighted a relative dearth of evidence relating to interventions in adults with bipolar disorder and to nutritional and sleep interventions. Future research could help establish lifestyle interventions as a core component of mental health care.