This cross-sectional study examined the associations between waking movement behaviour composition and depressive symptoms, self-rated health (SRH) and eating-disorder (ED)-related symptomatology (SCOFF) in university students using compositional data analysis (CoDA) and isotemporal substitution modelling. Data were collected through an anonymous web-based survey among students enrolled at the University of Milan, Italy. The analytical sample included 2636 participants. International Physical Activity Questionnaire (IPAQ) was used to measure daily time spent in moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and sedentary behaviour (SB) and analysed as a three-part composition. Outcomes included depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), SRH and SCOFF score. In adjusted compositional regression models, a higher relative proportion of MVPA was associated with lower depressive symptoms (β = -0.39, 95% confidence interval [CI]: -0.53 to -0.24) and higher SRH (β = 0.11, 95% CI: 0.08-0.13), whereas a higher relative proportion of SB was associated with higher depressive symptoms (β = 0.42, 95% CI: 0.21-0.64) and lower SRH (β = -0.11, 95% CI: -0.14 to -0.07). LPA was not significantly associated with outcomes. Isotemporal substitution analyses showed that reallocating 15 min from SB to MVPA was associated with lower PHQ-9 scores (-0.114, 95% CI: -0.156 to -0.072), higher SRH (0.031, 95% CI: 0.024-0.038) and SCOFF score (β = 0.04, 95% CI: 0.00-0.07). These findings suggest that, within the daily movement composition, increasing a greater relative allocation of time to MVPA at the expense of sedentary time is associated with modestly more favourable mental and perceived health in university students.
Background:Body size across the life course has been associated with long-term mental health outcomes, yet most previous studies have examined body size at a single developmental stage. Whether changes in relative body size from childhood to adulthood represent a distinct life-course marker of vulnerability to later depression and anxiety remains insufficiently understood. We examined the associations between child-to-adult body size changes and the risk of depression and anxiety and explored whether lifestyle factors and chronic diseases partly explained these associations. Methods:This study included 447,821 participants from the UK Biobank. Childhood body size at age 10 years was retrospectively self-reported as relative body size, and adult body size was assessed using measured body mass index (BMI) at baseline. Depression and anxiety were identified from electronic health records questionnaires, including the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7. Cox proportional hazards models were used to estimate associations with incident diagnoses, and mixed-effects linear regression models were used to examine symptom severity scores. Exploratory mediation analyses were conducted to assess the extent to which lifestyle factors and chronic diseases, including type 2 diabetes (T2D), hypertension and cardiovascular disease (CVD), statistically accounted for the observed associations. Results:In the fully adjusted models, childLow-adultHigh group had the highest risk of major depression (HR: 1.90, 95% CI: 1.79-2.01) and anxiety (HR: 1.58, 95% CI: 1.48-1.68) compared with the childAverage-adultAverage group. Unhealthy lifestyle factors and chronic diseases together statistically accounted for 21.9% of the association between the childLow-adultHigh group and major depression and 22.2% of the association between the childLow-adultHigh group and anxiety. Conclusions:Distinct body size changes from childhood to adulthood are associated with differential risks of depression and anxiety. Individuals transitioning from childhood leanness to adult heaviness may represent a particularly vulnerable life-course group. These findings support the importance of life-course approaches to understanding mental health vulnerability and identifying opportunities for early prevention.
Background:Sensory processing difficulties are increasingly recognized in major depressive disorder (MDD), with patients often exhibiting heightened sensitivity, avoidance, and low registration. However, the temporal stability of these patterns-trait vs. state-remains unclear. Methods:In this longitudinal study, 45 adult inpatients with MDD were assessed using the Adolescent/Adult Sensory Profile (AASP) at admission and 3 months later; 34 completed both assessments. Clinical variables included depression (Hamilton Depression Rating Scale [HDRS-17]), anxiety (Hamilton Anxiety Rating Scale [HARS]), anhedonia (Snaith-Hamilton Pleasure Scale [SHAPS]), self-esteem (Rosenberg Self-Esteem Inventory [RSEI]), and psychomotor retardation (Clinical Outcomes in Routine Evaluation [CORE]). Nonparametric tests examined sensory changes and associations with clinical outcomes. Results:At follow-up, 61.8% of participants showed clinical improvement and 44.1% achieved remission. Significant decreases in low registration and sensory sensitivity, along with increased sensation seeking, indicated that sensory processing is dynamic and partially state-dependent. Sensory avoidance remained stable and was more pronounced in recurrent MDD. Patients with clinical improvement or remission had sensory profiles closer to normative ranges. Higher sensitivity and avoidance correlated with more severe depression, anxiety, and lower self-esteem, while greater sensation seeking was associated with better outcomes. Conclusions:Sensory processing profiles in MDD are state-dependent and linked to clinical changes. These findings support the relevance of sensory traits as potential clinical markers and therapeutic targets. Personalized interventions addressing sensory processing may contribute to improved treatment outcomes. Further longitudinal and multimodal research is needed to clarify their predictive value. Trial Registration: ClinicalTrials.gov identifier: NCT05686668.
Background/Objective:Major depressive disorder (MDD) exhibits significant heterogeneity, and identifying these distinct biological subtypes aids clinical intervention. In this study, we employed functional gradient and Hydra clustering methods to distinguish subtypes of depression. Method:Imaging data were derived from a large-scale, multicenter MDD imaging database, comprising 1067 patients with MDD and 907 healthy controls (HCs). Based on the principal functional gradient, the Hydra method was employed to distinguish subtypes of MDD. We employed the Mann-Whitney U-test to compare functional gradient abnormalities across different subtypes of MDD while simultaneously conducting imaging transcriptomics analysis. Results:Using principal functional gradients, we identified two subtypes of MDD. Compared with HCs, subtype 1 exhibited abnormal functional gradient values in the dorsal attention network (DAN), ventral attention network (VAN), limbic network (LIB), frontoparietal network (FTP), and default mode network (DMN); subtype 2 exhibited abnormal functional gradient values in the visual network (VIS), somatosensory network (SMT), DAN, VAN, and DMN. Transcriptomics revealed that subtype 1 functional gradient abnormalities were significantly correlated with theory mind, 5-hydroxytryptamine (5-HT) 1B; subtype 2 functional gradient abnormalities were significantly correlated with motor function, dopamine D2 receptor, and norepinephrine transporter (NET). Conclusions:Our research deepens the understanding of the biological diversity of MDD, providing a biologically grounded framework for stratifying patients, which may inform the future design of hypothesis-driven clinical trials targeting specific cognitive or sensorimotor circuits.
Background:In Bangladesh, women experience common mental health conditions like depression and anxiety at twice the rate of men, yet they are only half as likely to seek treatment. There were instances of misdiagnosis reported among married women. This study aims to assess the prevalence, key determinants and diagnostic accuracy of anxiety and depression among married women in Bangladesh. Methodology:We used the largest cross-sectional nationally representative Bangladesh Demographic and Health Survey (BDHS) 2022 that sampled 18,605 married women, aged 15-49 years. We utilised complex survey-adjusted binary and multinomial logistic regression models to explore the association between mental health diagnoses and sociodemographic factors. Results:One in three women reported symptoms of anxiety and depression without a clinical diagnosis. Significant regional variation was observed, with women in Dhaka, Mymensingh and Rajshahi less likely to be symptomatic but undiagnosed. Protective factors included higher education, internet access, and household wealth, while media exposure, mobile phone ownership, and attitudes accepting violence increased risk. Women accepting violence had 1.18 times (95% CI = 1.07-1.30) higher odds of being symptomatic but undiagnosed. Those involved in household decision-making had 26% (95% CI = 1.14-1.40) higher odds compared to women who were correctly identified. In contrast, women with secondary and higher education had 17% (95% CI = 0.73-0.95) and 20% (95% CI = 0.66-0.97) lower odds, respectively. Conclusion:Targeted interventions through health literacy interventions are needed in regions with higher rates of symptomatic but undiagnosed cases. Awareness campaigns should also address the harmful effects of media exposure, limited digital access and social norms that normalise violence.
Objectives:Mixed features in major depressive disorder (MDD)-the presence of manic symptoms during major depressive episodes (MDEs)-are associated with adverse clinical outcomes. We investigated the prevalence and clinical correlates of mixed features among Korean women with recurrent MDD. Method:Data (n = 3000) were drawn from the Korean Mood Disorder Genetic Study-Depression, a nationwide case-control study recruiting women aged ≥30 years with recurrent MDD from 47 hospitals across South Korea. Structured clinical interviews assessing depressive symptoms, family history, comorbidities, and psychosocial functioning were administered. Mixed features during MDEs were defined per Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Generalized linear models (GLMs) examined associations between mixed features and clinical correlates. Results:The worst-MDE-based prevalence of mixed features was 4.6%. A family history of manic episodes (odds ratio [OR] = 3.36, 95% confidence interval [CI]: 1.67-6.36) and of MDEs (OR = 1.90, 95% CI: 1.41-2.55) was significantly associated with mixed features. Five worst-MDE symptoms were independently associated with mixed features: increased weight (OR = 2.19, 95% CI: 1.16-4.09), late insomnia (OR = 1.84, 95% CI: 1.07-3.41), slow or mixed thoughts (OR = 1.93, 95% CI: 1.18-3.33), suicidal ideation (OR = 1.96, 95% CI: 1.04-3.94), and diurnal mood variation (OR = 1.94, 95% CI: 1.34-2.81). Mixed features were associated with mood-stabilizer use (lifetime use OR = 2.21, 95% CI: 1.38-3.42; current use OR = 2.53, 95% CI: 1.58-3.92), panic disorder (OR = 2.10, 95% CI: 1.46-2.99), premenstrual syndrome symptoms (rate ratio [RR] = 1.22, 95% CI: 1.08-1.37), and damage by suicide attempts (RR = 1.66, 95% CI: 1.17-2.07). Conclusions:Although less prevalent in this clinically ascertained sample than in Western samples, mixed features in recurrent MDD exhibit distinct clinical patterns. This finding underscores the importance of screening for mixed features, particularly when associated depressive symptoms are present, to inform early detection and treatment planning.
Background:Major depressive disorder (MDD) has become one of the diseases that seriously affects the quality of life and social function of patients. Electroconvulsive therapy (ECT) is an important method for treating mental disorders. This study aims to conduct a comparison of symptomatic improvement in patients with MDD across different age groups following ECT, thereby providing more precise and personalized treatment plans. Methods:PubMed, Cochrane Library, CNKI, Wanfang, and other databases were searched for related studies from self-built databases until February 2025. The retrieved studies were then subjected to a meta-analysis using R software. Based on the assessment of heterogeneity across studies, either a fixed-effect model or a random-effect model was selected for data synthesis. Results:A total of 15 eligible articles were included in this meta-analysis, involving 1617 patients with MDD. The results indicated ECT could reduce the scores of the Hamilton Depression Rating Scale (HAMD), Montgomery-Åsberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HAMA). Additionally, it could increase the scores of the Mini-Mental State Examination (MMSE). However, no statistical significance was observed on the subscales of the Wechsler Memory Scale (WMS). Subgroup analysis and meta-regression revealed that the older patients (>60 years old) may benefit more significantly in improving depressive symptoms (HAMD and MADRS) and WMS recognition memory. No significant age-related differences are observed in HAMA, MMSE, or other WMS subtests. Conclusions:ECT demonstrates therapeutic effects across all age groups of patients with MDD. The older group seemed to benefit more from this treatment modality compared to other age groups. These findings contribute to a better understanding of the differential effects of ECT in patients with MDD of different ages, which may guide clinical decision-making.
Background:Veterinarians have been identified as a high-risk occupational group for mental health problems; however, evidence regarding their mental health status in Türkiye remains limited. This study aimed to examine the prevalence of depression, anxiety, stress, and resilience among veterinarians in Türkiye. Methods:A cross-sectional study was conducted with 821 veterinarians (Mage = 34.94, SD = 8.60; range 19-65) working in both public and private sectors in Türkiye. Participants were recruited using a stratified sampling method based on sex, employment sector, and geographical region. Data were collected using the Depression, Anxiety, and Stress Scale (DASS-21) and the Brief Resilience Scale (BRS). Independent samples t-tests, Pearson correlation analyses, and chi-square tests were used to analyze the data. Results:The findings indicated that 34% of participants reported depression, 35% anxiety, and 39% severe or extremely severe stress levels. Approximately 35% of veterinarians were found to have low resilience. Female veterinarians reported significantly higher levels of depression, anxiety, and stress, as well as lower resilience, compared to males. In addition, veterinarians working in the public sector exhibited significantly lower levels of depression, anxiety, and stress than those working in the private sector. Conclusion:The results indicate that mental health problems are prevalent among veterinarians in Türkiye and vary across demographic and occupational groups. These findings contribute to the limited evidence base on veterinary mental health in middle-income country contexts.
Executive functions (EFs) and parental styles are key determinants of adolescent mental health. This study investigates the mediating role of EFs in the relationship between parenting styles (communicative, hostile, and neglectful) and anxiety and depression symptoms in a sample of 165 adolescents (50.9% boys and 49.1% girls) from 12 to 16 years old (mean age 13.29) from schools with varying socioeconomic vulnerability levels. Participants completed the Child's Report of Parental Behavior Inventory, the Behavior Rating Inventory of Executive Function 2 and the Revised Child Anxiety and Depression Scale. The results show that adolescents in high-vulnerability schools exhibit significantly higher anxiety and depression symptoms and perceive lower parental communication from both mothers and fathers compared to those in low-vulnerability schools. No significant differences were observed in EFs difficulties based on school vulnerability. Regression analyses indicate that parental communication predicts lower levels of anxiety and depression symptoms, whereas paternal neglect emerges as a specific risk predictor. Mediation models reveal that EFs deficits, specifically in cognitive flexibility and working memory, serve as the primary mechanism linking parenting styles to emotional adjustment. These findings underscore the importance of parental communication as a secure environment that may foster not only cognitive development but also mentalization (or reflective functioning). We conclude that school-based interventions should prioritize EFs training as an equity-based tool to protect the well-being of adolescents in high-vulnerability settings.
Background:Suicide-loss survivors (SLSs) experience substantial and often enduring psychological burden. These difficulties are compounded by public stigma, underscoring the need for scalable approaches to shift attitudes at the population level. In this study, we examined whether brief survivor-narrative videos can reduce public stigma of SLSs. Methods:In a randomized controlled trial, 1351 adults (18-50) completed baseline measures and were allocated to view either a brief SLS narrative or a psychoeducational control. Public stigma toward SLSs and trait impressions were assessed at baseline and postexposure. Results:Relative to control, the SLS video arm showed clear improvements immediately and at 30 days: stigma scores were lower and trait impressions more favorable, with attenuation over time. Item-level analyses indicated sizable immediate reductions for "Disconnected" (-24%) and "Cowardly" (-16%), and smaller but significant decreases for "Immoral" and "Irresponsible" (-12% each). Conclusions:Brief survivor-narrative videos can shift public attitudes toward SLSs and maintain part of that change over 1 month. As a low-cost, scalable complement to postvention, brief video contact offers a practical lever to improve the social climate surrounding SLSs. Deployed widely and reinforced over time, it can move communities from blame to empathy, strengthen everyday support, and advance survivors' recovery.
Background:Evidence suggests that people with glaucoma may experience more depressive symptoms than those without glaucoma, but prior estimates have been limited by heterogeneous ascertainment and insufficient separation of comparative, prevalence, and longitudinal evidence. Methods:We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, Wanfang, VIP, CNKI, ChiCTR, and ClinicalTrials.gov to March 27, 2026. Eligible studies reported depression outcomes among individuals with glaucoma; studies included in the primary comparative analysis additionally required a non-glaucoma comparison group. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale (NOS) for cohort/case-control studies and Joanna Briggs Institute (JBI) tools for cross-sectional studies. Random-effects meta-analyses used restricted maximum likelihood (REML) as the primary estimator; DerSimonian-Laird models were sensitivity analyses. Certainty of evidence was assessed using the GRADE framework adapted for observational evidence. Results:Forty-nine studies were included qualitatively. Sixteen studies including 14,030 glaucoma participants and 4,472,723 controls contributed to the primary odds ratio meta-analysis. Glaucoma was associated with higher odds of depression (OR, 2.80; 95% CI, 1.66-4.74; I 2 = 95.95%; approximate prediction interval 0.32-24.47). Results remained significant across sensitivity analyses excluding self-reported glaucoma studies, unclear glaucoma ascertainment, and a very large database study. Thirty-eight studies including 21,705 patients with glaucoma contributed to the single-group prevalence meta-analysis; pooled depression prevalence was 26.03% (95% CI, 21.10%-31.64%; prediction interval 5.98%-66.04%). Longitudinal evidence was limited and heterogeneous; one UK Biobank cohort suggested a longitudinal association with incident hospitalized depression among participants with glaucoma (HR, 1.54; 95% CI, 1.01-2.34). GRADE certainty was very low for the comparative, prevalence, and longitudinal evidence domains. Conclusions:Very low-certainty observational evidence suggests that depression or depressive symptoms are more common among individuals with glaucoma; however, whether glaucoma precedes, contributes to, or results from depressive symptoms remains uncertain. The observed association may reflect complex bidirectional relationships between glaucoma-related visual burden and depressive symptoms. Ophthalmic care should incorporate pragmatic depression awareness and referral pathways, while future longitudinal studies should use standardized glaucoma and depression ascertainment with adequate adjustment for visual, clinical, and socioeconomic confounders.
Antenatal depression affects a substantial proportion of pregnant women and is associated with adverse maternal and infant outcomes, particularly in settings where specialist mental health services are limited. The purpose of this narrative review was to synthesize evidence on the effectiveness and implementation feasibility of nonpharmacological interventions for antenatal depression in low-resource settings, with particular attention to task sharing, cultural adaptation, and relevance to Palestine. A targeted search of PubMed, ScienceDirect, SpringerLink, JMIR Publications, Google Scholar, and an Arabic-language journal was conducted to 30 September 2025. Eligible studies included pregnant women with depressive disorders or clinically relevant depressive symptoms, as well as prevention-oriented antenatal samples in which depressive symptoms were a prespecified outcome. Eligible publications evaluated nonpharmacological interventions using randomized, quasi-experimental, or prospective pre-post designs; linked reports of pregnancy or neonatal outcomes from otherwise eligible antenatal intervention programs were also considered. Twenty-two studies met the inclusion criteria. Generally favorable findings were reported for cognitive behavioral therapy (CBT)- and interpersonal psychotherapy (IPT)-based interventions delivered in individual, group, task-shared, and brief clinic-based formats, although the strength and consistency of evidence varied by study design and population. Favorable findings were also reported for depression-specific acupuncture, brief mindfulness and mind-body programs, nurse-supported counseling, and culturally or spiritually integrated approaches, although the strength of inference varied by study design. Supervised digital formats and task-shared models involving primary health workers, nurses, and midwives showed promise for extending care in constrained systems, whereas unguided self-help approaches produced less consistent findings. Implementation reporting was uneven: service integration, task sharing, brief delivery, and supervised formats supported preliminary feasibility, whereas formal measures of acceptability, fidelity, cost, population reach, and sustainability were infrequently reported. The review identified several potentially implementable nonpharmacological options for antenatal depression in low-resource settings, particularly brief psychological therapies, task-shared models, selected supervised mindfulness formats, nurse-supported counseling, and culturally adapted programs. However, locally codesigned pragmatic studies are required before broad implementation in Palestine and similar humanitarian or resource-constrained settings.
Background:Depressive symptoms (DSs) are highly prevalent among medical students and may adversely affect both student well-being and future healthcare quality. Although personality traits (PTs) are closely associated with mental health, the psychological processes underlying these associations remain incompletely understood. This study examined the associations between the five PT dimensions and DS and explored whether psychological capital (PsyCap) and perceived stress (PS) statistically mediated these associations. Methods:A multicenter cross-sectional survey was conducted among 583 third-year undergraduate clinical medicine students from three medical universities in China. Standardized questionnaires were administered to assess PTs, PsyCap, PS, and DS. Correlation, regression, and sequential mediation analyses were performed. Results:Correlation analyses showed that neuroticism was negatively correlated with PsyCap and positively correlated with PS and DS, whereas extraversion, openness to experience, agreeableness, and conscientiousness demonstrated the opposite pattern (all p < 0.001). Regression analyses indicated that neuroticism, openness to experience, agreeableness, and conscientiousness were significantly associated with DS (β = 0.39, -0.14, -0.15, -0.10, respectively, all p < 0.001), whereas the direct association between extraversion and DS was not statistically significant (β = -0.05). Mediation analyses supported statistically significant indirect associations through PsyCap alone, PS alone, and the proposed sequential pathway through PsyCap and PS. Among the five PT dimensions, the association between extraversion and DS was primarily reflected through the indirect pathways. Conclusion:The findings suggest that PTs may be associated with DS through psychological resources and stress appraisal. By integrating PsyCap and PS into a sequential mediation framework, this study provides an expanded perspective on the psychological processes linking PTs and DS among medical students. Given the cross-sectional design, the proposed mediation pathways should be interpreted as statistical associations rather than causal relationships. Future longitudinal and intervention studies are needed to further evaluate these associations.
Background:Despite being a modifiable risk factor for cognitive decline, the influence of depressive symptoms on cognitive decline lacks a systematic assessment of its cumulative exposure intensity, temporal dimensions, and dynamic change. Aim:To systematically evaluate the multidimensional associations of depressive symptom exposure-including cumulative exposure, burden, duration, and dynamic change patterns-with incident cognitive decline, by adopting an analytical framework that integrates "static accumulation and dynamic evolution." Methods:Among 8847 Health and Retirement Study (HRS) participants free of cognitive decline at baseline, cumulative depressive symptoms were quantified as the area under the curve (AUC) across 2012-2016 waves. A cut-point was identified by maximizing the log-rank statistic for cognitive decline risk within a clinically relevant range (2.5-3.5) and used to define cumulative burden and high-exposure duration. Dynamic symptom patterns across three waves were identified, and their interaction with cumulative burden was examined. Multivariable Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cognitive decline risk associated with these exposure metrics. Results:During 3.67 median follow-up years, 2311 incident cognitive decline cases occurred. Cognitive decline risk rose with escalating cumulative depressive exposure: the highest tertile (HR 1.42; 1.28-1.58), cumulative burden ≥0 (HR 1.34; 1.21-1.49), longest duration (HR 1.29; 1.12-1.48), and a progressively worsening trend (HR 1.52; 1.25-1.84) all significantly increased risk. Conclusions:Our findings demonstrate that the effect of depressive symptoms on cognitive decline is cumulative, time-dependent, and dynamic. These results emphasize that sustaining a stable, low-severity depressive symptom profile is essential for lifelong cognitive health.
Background:Social anxiety and avoidance behaviors are prevalent among breast cancer patients, yet their interrelationships with protective factors such as spiritual well-being remain poorly understood. Network analysis offers a novel approach to identify central and bridge nodes that may serve as key targets for psychosocial intervention. Methods:We conducted a cross-sectional study of 302 female breast cancer patients from a tertiary hospital in China. Participants completed the Social Anxiety Scale (SAS_1), Social Avoidance Scale (SAS_2), and the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp). A network model was constructed to examine the interrelationships among these constructs, with centrality and bridge centrality indices used to identify influential nodes. Results:Spiritual well-being-particularly items such as "strength from faith" and "confidence in recovery"-showed the highest strength centrality, indicating its central role in the psychological adaptation network. Social avoidance emerged as the strongest bridge node, connecting spiritual well-being with social anxiety. Surgical approach did not significantly alter the global network structure, but subgroup analyses revealed distinct node-level bridge strengths, suggesting differential psychological adaptation pathways. Conclusion:Spiritual well-being occupies a central position in the psychological network of breast cancer patients, and social avoidance shows the strongest bridging function between spiritual resources and emotional symptoms. These findings support the integration of spiritual assessment and targeted avoidance-reduction strategies into supportive care. Future research should validate these networks in larger samples and develop node-specific interventions to improve psychological adjustment.
Background:Several lines of evidence suggest that vitamin B6 has potential as an antidepressant. It plays a crucial coenzyme role in the synthesis of the neurotransmitters serotonin, gamma-aminobutyric acid (GABA) and dopamine, which are central to mood regulation, and it has been shown that increasing availably of vitamin B6 above normal levels increases concentrations of serotonin and GABA. Furthermore, epidemiological evidence points to vitamin B6 deficiency as a risk factor for depression, and to high vitamin B6 levels as protective. Therefore, we asked whether taking 100 mg vitamin B6 as pyridoxine daily for 1 month would reduce depression symptoms, measured with the Depression, Anxiety and Stress Scales (DASS) questionnaire, which also assesses anxiety and stress. Methods:We recruited 267 participants from the general population (215 female) and double blind randomised them to receive either placebo, vitamin B6 or vitamin B12 (1000 µg). Using baseline DASS scores, we divided participants into a group classified as having mild or more severe depression symptoms at baseline (N = 58) and a larger group classified as non-depressed. Results:Only within the former group, vitamin B6 produced a selective reduction in depression symptoms compared to placebo or vitamin B12 with a very large effect size (partial η 2 = 0.20). We also found evidence that participants whose DASS depression scores narrowly failed to meet criterion for moderate depression (N = 52) experienced a slightly smaller but still statistically substantial reduction in symptoms (partial η 2 = 0.17). We repeated the analysis procedure for anxiety and stress scores but found no significant effects. Conclusions:We have shown that high-dose vitamin B6 has therapeutic potential for depression, and large-scale clinical trials with patients should now be conducted to determine whether these findings from our mostly female sample generalise to males, to quantify the dose-response relationship, and to evaluate its potential as an adjunct to existing treatments versus monotherapy, and to elucidate which factors, for example, presence of inflammation, predict responsiveness to the intervention.
Insufficient responses to available treatments for major depressive disorder (MDD) underscores the necessity for innovative therapeutic strategies. This study investigated the efficacy of adjunctive rosiglitazone, an antidiabetic agent with neuroprotective and anti-inflammatory effects, for MDD. In this 6-week randomized, parallel-group, double-blind, placebo-controlled clinical trial, patients with MDD were assigned to receive sertraline along with either rosiglitazone 2 mg or a matched placebo q12 h. Participants were evaluated using the Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4, and 6. The difference in its score changes to the endpoint was the primary outcome. Side effects were documented as well. The participants had comparable baseline characteristics. A significant time -treatment interaction effect was observed for HDRS scores ( η P 2 = 0.052), with the rosiglitazone group experiencing significantly greater reductions at weeks 2 (Cohen's d = 0.507), 4 (Cohen's d = 0.556), and 6 (Cohen's d = 0.541) compared to the placebo group. Additionally, the rosiglitazone group demonstrated significantly higher response rates until weeks 4 (50.0% vs. 24.2%) and 6 (84.4% versus 51.5%). By week 6, the remission rate was nonsignificantly higher in the rosiglitazone group (18.8%) than in the placebo group (9.1%). Side effect frequencies were comparable. In conclusion, rosiglitazone was beneficial for depressive symptoms of patients with MDD safely and tolerably. Further long-term, large-scale studies are recommended to confirm this evidence. Trial Registration: ClinicalTrials.gov identifier: IRCT20090117001556N152.
Background:While antidepressant side effects are often expected to diminish with continued treatment, empirical evidence remains limited. This study investigates co-trajectories of depressive severity with side-effect burden (SEB) and associated factors in patients with major depressive disorder (MDD). Methods:We analyzed longitudinal data from 1377 MDD outpatients across three Chinese multicenter studies (2015-2022), with assessments at baseline, weeks 2, 4, 8, 12, and 24. Depression severity was measured using the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16). At the same time, SEB was quantified using the frequency, intensity, and burden of side effects rating (FIBSER). Dual-trajectory modeling was used to identify distinct SEB and depression severity trajectories, with linear mixed-effects models comparing depression changes across SEB groups. Results:Four SEB trajectories were identified: no SEB (41.5%), early-onset SEB (29.1%), late-onset SEB (14.7%), and persistent SEB (13.9%). Depressive severity followed three trajectories: mild-responsive (66.6%), moderate-progressive (18.7%), and chronic-severe (14.7%). Persistent SEB was associated with higher baseline depression severity (OR = 1.13, 95% CI: 1.08-1.17), antidepressant combination (OR = 3.7, 95% CI: 1.52- 9.02), and poorer treatment outcomes. 7.3% exhibited concurrent chronic-severe depressive severity and persistent SEB. Female (OR = 1.95, 95% CI: 1.11-3.42), younger age (OR = 5.02, 95% CI: 2.63-9.55), higher education (high school: OR = 2.5, 95% CI: 1.12-5.36; bachelor and above: OR = 2.68, 95% CI: 1.24-5.82), and combination antidepressant (OR = 8.27, 95% CI: 2.69-25.45) were significant risk factors for concurrent severe symptoms and persistent SEB. Conclusion:Persistent antidepressant side effects coevolve with unfavorable depression trajectories over 6 months. Clinicians should prioritize early monitoring and tailored interventions for high-risk subgroups, particularly those with severe baseline symptoms or on combination therapy. These findings underscore the importance of continuous monitoring and personalized interventions to manage antidepressant side effects effectively.
The comorbidity of mood disorders (MDs), represented by depression and anxiety, with chronic somatic diseases (CDs), particularly cardiometabolic conditions, poses a significant global public health challenge, markedly increasing the risk of adverse prognoses and all-cause mortality. Epidemiological studies indicate that ~36% of patients with multimorbidity exhibit psychosomatic comorbidity, with higher risk populations concentrated among females, older adults, and socioeconomically disadvantaged individuals. This review systematically analyzes the epidemiological distribution patterns of MD-CD comorbidity, with the strongest emphasis on cardiometabolic diseases-diabetes, metabolic syndrome (MetS), obesity, hypertension (HTA), and cardiovascular disease (CVD)-for which the mechanistic data are most developed, while also addressing osteoarthritis, psoriasis, inflammatory bowel disease (IBD), cancer, and neurological disorders. By integrating molecular mechanisms with clinical evidence, we highlight core pathological pathways and critically evaluate the strength of evidence supporting each: hypothalamic-pituitary-adrenal (HPA) axis dysfunction and insulin resistance (IR), substantiated by clinical data and Mendelian randomization; NLRP3 inflammasome-mediated neuroinflammation as a transdiagnostic inflammatory node; gut-brain axis dysregulation involving bile acid-GLP-1 signaling and gut-derived metabolites such as trimethylamine N-oxide (TMAO); and the kynurenine pathway (KP) as a branched metabolite axis with organ-specific consequences. Sex-specific mechanisms, particularly estrogen-regulated neuroendocrine and metabolic pathways, are identified as consistent biological modifiers of this comorbidity. A bidirectional vicious cycle underpins MD-CD comorbidity: metabolic abnormalities exacerbate limbic system dysfunction via HPA-axis hyperactivity, neuroinflammatory cascades, and disrupted gut-brain signaling, while MDs aggravate metabolic dysregulation through neuroendocrine disturbances and reduced treatment adherence.
Background:Adolescent major depressive disorder (MDD) is clinically heterogeneous, with sleep disturbance often emerging as a prominent but variably expressed symptom dimension. This study aimed to identify latent symptom profiles in drug-naïve adolescents with MDD and examine their associations with recorded trauma/stressor exposure and neuroendocrine markers. Methods:This cross-sectional study included 711 drug-naïve adolescents with MDD. Latent profile analysis (LPA) was conducted using 16 symptom indicators derived from the Hamilton depression rating scale (HDRS), Hamilton anxiety rating scale (HAMA), and Pittsburgh sleep quality index (PSQI). Multinomial logistic regression examined associations of recorded trauma/stressor exposure and neuroendocrine markers with profile membership. Results:A three-profile solution was retained: low overall symptoms (Profile 1; n = 200, 28.1%), PSQI-elevated subjective sleep disturbance (Profile 2; n = 215, 30.2%), and high overall symptoms (Profile 3; n = 296, 41.6%). Recorded family trauma/stressor exposure and violent incident exposure were associated with higher odds of Profile 3 membership relative to Profile 1, and these associations remained significant after neuroendocrine markers were added. Higher standardized testosterone (T) showed a modest association with Profile 3 membership, whereas FT3 showed only a marginal association. However, adding neuroendocrine markers did not significantly improve model fit beyond trauma-related variables. Conclusion:LPA identified three clinically interpretable symptom profiles in adolescent MDD, including a profile characterized primarily by elevated PSQI-assessed subjective sleep disturbance. Recorded trauma/stressor exposure was associated with the high overall symptom profile, whereas neuroendocrine markers showed limited incremental value. These findings highlight multidimensional symptom profiling and trauma assessment in adolescent depression, while suggesting that neuroendocrine findings should be considered exploratory.
