Risk Of Major Depressive Disorder Research Articles

Exploring the association between urticaria subtypes, anxiety, and depression and potential role of gut microbiota.

Exploring the association between urticaria subtypes, anxiety, and depression and potential role of gut microbiota.

NRXN3-NLGN1 complex influences the development of depression induced by maternal separation in rats.

NRXN3-NLGN1 complex influences the development of depression induced by maternal separation in rats.

The human cerebral cortex morphology in neuropsychiatric disorders: A causal inference based on Mendelian Randomization.

The human cerebral cortex morphology in neuropsychiatric disorders: A causal inference based on Mendelian Randomization.

107-OR: Impact of Microvascular Complications on Severe Mental Illness Risk in Patients with Type 2 Diabetes—A Nationwide Cohort Study in Taiwan

Introduction and Objective: This study aimed to evaluate the likelihood of developing severe mental illnesses (SMI) —including schizophrenia, bipolar disorder, and major depressive disorder (MDD) among type 2 diabetes (T2D) patients with and without microvascular complications. Methods: We analyzed data from Taiwan National Health Insurance Research Database, and 394,659 matched pairs of microvascular and non-microvascular patients were selected. Multivariable Cox proportional hazards models and Kaplan-Meier method were used for assessment. Results: T2D patients with microvascular complications had a significantly higher risk of SMI. Schizophrenia risk increased with one microvascular disease [aHR (95% CI) 1.11 (1.01, 1.22)], two [1.38 (1.08, 1.76)], and three [aHR (95% CI) 2.29 (1.06, 4.97)]. Bipolar disorder risk was elevated with one microvascular complication [1.17 (1.09, 1.25)], and two [1.27 (1.06, 1.52)]. Risk of MDD increased with one microvascular disease [1.20 (1.18, 1.23)], two [1.41 (1.32, 1.50)], and three [1.53 (1.26, 1.86)]. Diabetic neuropathy has a stronger association with SMI compared to diabetic nephropathy and retinopathy. Conclusion: This nationwide cohort study showed that T2D patients with microvascular complications are at a heightened risk of developing SMI compared to those without microvascular disease. Disclosure Y. Yen: None. W. Cheng: None. F. Yen: None. H. Lin: None. C. Hwu: None. C. Hsu: None. Funding Taiwan Ministry of Health and Welfare Clinical Trial Center (NSTC 113-2321-B-039-006); China Medical University Hospital (DMR-111-105; DMR-112-087; DMR-113-009; DMR-113-156); Taipei Veterans General Hospital (V111C-188, V112C-164, V113C-166); National Science and Technology Council, R.O.C. (MOST 110-2314-B-075-027-MY3)

Prospective prediction of first onset of major depressive disorder in midlife using machine learning.

In this paper we leverage machine learning (ML) models to prospectively predict the first onset of Major Depressive Disorder (MDD), one of the most common and disabling mental health conditions. While such prediction models hold potential for enabling early interventions, few studies have applied ML approaches to this task, and those that have are heterogeneous in nature. Moreover, the clinical utility of these predictive models remains largely unexamined. Data stemmed from CoLaus|PsyCoLaus, a population-based cohort study. In total, 1350 participants, age 35-66 years without lifetime MDD at baseline participated in the physical and psychiatric baseline and at least one psychiatric follow-up evaluation. Models based on logistic regression, elastic net, random forests, and XGBoost were trained using an extensive array of psychosocial, environmental, biological, and genetic predictors. Discriminative performance, calibration, clinical utility, and individual predictor contributions were assessed using nested cross-validation. Discriminative performance was comparable between models (areas under the precision-recall curve between 0.36 and 0.38; areas under the receiver operating characteristic curve between 0.65 and 0.68). Decision curve analysis suggested clinical utility of logistic regression, elastic net, and random forests for threshold probabilities between 10% and 40%. Across all models, neuroticism, sex, and age were the most important predictors. Although the prediction models achieved discriminative performance levels above chance, further refinement is necessary. The addition of biological and genetic predictors did not elevate performance markedly. Additional research seems warranted given the limited number and heterogeneous nature of existing studies, the burden associated with MDD, and the potential to improve overall outcomes for people at risk for MDD.

Medical conditions and the risk of subsequent major depressive disorder: a nationwide, register-based, retrospective cohort study.

Medical conditions and the risk of subsequent major depressive disorder: a nationwide, register-based, retrospective cohort study.

Autoimmune thyroid disease is a risk factor for mood disorders, a Mendelian randomization study.

Autoimmune thyroid disease is a risk factor for mood disorders, a Mendelian randomization study.

The role of the brain-bone axis in skeletal degenerative diseases and psychiatric disorders, A genome-wide pleiotropic analysis.

The role of the brain-bone axis in skeletal degenerative diseases and psychiatric disorders, A genome-wide pleiotropic analysis.

Mediating effects of gastroesophageal reflux disease and smoking behavior on the relationship between depression and chronic obstructive pulmonary disease: Trans-ethnic Mendelian randomization study.

Mediating effects of gastroesophageal reflux disease and smoking behavior on the relationship between depression and chronic obstructive pulmonary disease: Trans-ethnic Mendelian randomization study.

Major-depressive-disorder-associated dysregulation of ZBTB7A in orbitofrontal cortex promotes astrocyte-mediated stress susceptibility.

Major-depressive-disorder-associated dysregulation of ZBTB7A in orbitofrontal cortex promotes astrocyte-mediated stress susceptibility.

Serum vitamin levels and major depressive disorder: Age-dependent associations in the US adult population

This study used National Health and Nutrition Examination Survey (NHANES) data to explore the potential association of serum vitamins with major depressive disorder (MDD) among US adults, as well as the potential moderating role of age. This study screened eligible individuals aged ≥ 20 years from NHANES 2005 to 2006 and 2017 to 2018 cycle in the US. Multivariate-adjusted logistic regression models were used to explore the relationship between 5 serum vitamins and MDD. We built 3 models to adjust the potential confounders of 13 factors (age, gender, ethnicity, FIPR, education, hypertension, high cholesterol, diabetes, body mass index, sleep time, dietary quality, physical activity and alcohol consumption) on the outcome. Interaction analysis was performed to explore the moderating effects of age on such association. A total of 4278 participants were included, including 3133 (73.23%) individuals aged < 60 years and 1145 (26.76%) individuals ≥ 60 years. In Age < 60 years group, 229 (7.3%) participants had depressive symptoms. We only observed a negative association between vitamin D (VD) and depressive symptoms (OR = 0.986; 95% CI = 0.973–0.998). Among participants ≥ 60 years old, about 82 (7.71%) of the participation had depressive symptoms. Negative associations with the risk of MDD were found for vitamin A (VA) (OR = 0.212, 95% CI = 0.087–0.512) and VD (OR = 0.853, 95% CI = 0.798–0.912). In addition, we found there were significant interactions between both VA, vitamin E and age on depressive symptom (P = .027, P = .006, respectively). This study investigated the association between serum vitamins and major depression through analysis. The result showed that VD was negatively associated with severe depression in younger patients, while VA and vitamin E were negatively associated with severe depression in older patients. This study provides a new perspective for individualized treatment and intervention of age stratification in severe depression.

Biological aging acceleration in major depressive disorder: a multi-omics, multi-modal analyses

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels—including the brain—in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer’s disease, related dementia, and mortality among individuals with MDD in the UK Biobank. Evidence of depressive episode remission attenuated the association between MDD and systemic and brain proteomic aging acceleration. Finally, Mendelian randomization analyses revealed a causal effect of MDD on systemic and brain proteomic aging acceleration. Our results suggest a strong bidirectional association between MDD and biological aging acceleration. Biological aging acceleration, assessed by proteomic systemic and organ-specific clocks, can serve as a novel therapeutic target for treating MDD and for mitigating the long-term risks of adverse health outcomes associated with this condition.

MiR-34a rs2666433 and cognitive function in major depressive disorder: a clinical correlation analysis

Background Genetic factors play a crucial role in the development of major depressive disorder (MDD). Objectives This study aimed to investigate the association between the microRNA (miR)-34a rs266643 polymorphism and MDD, as well as its impact on cognitive function. Materials and methods Clinical data and blood samples were collected from 302 MDD patients and 306 healthy controls who met the predefined inclusion and exclusion criteria. The severity of MDD in patients was assessed using the Hamilton Rating Scale for Depression (HRSD). Cognitive function in MDD patients was evaluated using the Mini-Mental State Examination (MMSE), Stroop Color-Word Test (Stroop-C and Stroop-CW), and Montreal Cognitive Assessment (MoCA). Gene typing was performed using the Sanger sequencing method, while the relative expression level of miR-34a was quantified by RT-qPCR. Results The MDD group exhibited a significantly higher miR-34a expression fold change compared to the control group (p < 0.001). Among the genotypes, the AA genotype demonstrated the highest expression, followed by GA, with both being significantly greater than GG. The expression of miR-34a was positively correlated with HRSD, Stroop-C, and Stroop-CW scores but negatively correlated with MMSE and MoCA scores (p < 0.001). Carrying the A allele (OR = 1.468, p = 0.002) or the AA genotype (OR = 2.382, p = 0.001) was associated with an increased risk of MDD. Furthermore, patients with the AA genotype exhibited significantly poorer cognitive function compared to other genotypes. Conclusion The gene polymorphism of miR-34a rs2666433 was significantly associated with the severity of MDD as well as cognitive function.

INVESTIGATING THE GENETICS OF DEPRESSION IN A MULTIANCESTRAL COHORT OF CHILDREN AND ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

PV161 / #509Poster Topic:AS18 - Pediatric SLEBackground/PurposePatients with childhood-onset systemic lupus erythematosus (cSLE) have a higher prevalence of depression compared to healthy peers. Patients with cSLE also have a 10% greater risk of major depressive disorder (MDD) compared to those with adult-onset SLE (39% vs. 29%). Genetics plays a role in mood disorders and SLE susceptibility. Genome-wide association studies (GWAS) have identified &gt;100 genetic risk variants for each of depression and SLE. The cumulative effects of these variants can be combined into polygenic risk scores (PRS). Our study aims to test the association between genetic risk variants for (1) SLE and (2) MDD with depression, in a multiancestral cohort of children and adolescents with SLE.MethodsWe included patients followed in a tertiary care Lupus clinic from January 1, 2000, to December 31, 2023. All patients met ≥4 American College of Rheumatology (ACR) and/or Systemic Lupus International Collaborative Clinics (SLICC) criteria for SLE with data prospectively collected in a dedicated lupus database. Patients were genotyped on an Illumina multiethnic array, with un-genotyped single nucleotide polymorphisms (SNPs) imputed using TopMed as a referent. Ancestry was genetically inferred using principal components (PCs) and ADMIXTURE. We calculated weighted, additive PRSs for: 1) SLE (HLA and non-HLA) and 2) MDD using risk SNPs from the largest GWAS to date. We identified patients with depression as those with a depression diagnosis and/or persistent depressive symptoms over a course of at least 2 months prior to or following SLE diagnosis. We tested the association between each PRS and depression in univariate and multivariable-adjusted logistic regression models, adjusted for sex and 5 PCs (P&lt;0.017). We additionally carried out a sensitivity analysis focusing only on patients with a clinical depression diagnosis.ResultsOur study included 491 patients, 84% were female, with a median age of SLE diagnosis of 14 years (IQR: 11-15). There were 64 (13%) patients with a depression diagnosis, 130 (26%) with a depression diagnosis and/or persistent depressive symptoms. The majority of patients were of European (29%) and East Asian (27%) ancestry (Table 1). We did not observe a significant association between PRSs for either SLE (HLA and non-HLA) or MDD and depression (Table 2). Regarding SLE clinical features, the most common was arthritis (68%), followed by lupus nephritis (39%) and neuropsychiatric SLE (NPSLE; 25%). NPSLE was significantly associated with depression in univariate and multivariable-adjusted models (OR 2.37, 95% CI 1.51-3.73;P=0.0002). Sensitivity analyses demonstrated similar associations between the PRSs and clinical depression.Table 1:Demographic characteristics and clinical and laboratory featares of cohort (n=491)Table 2:Univariate and multivariable logistic regression results (n=491)ConclusionsIn a multiancestral cohort of children and adolescents with SLE, we did not observe a significant association between genetic loci for SLE and MDD and depression. This may be due to the limited generalizability of European SLE and MDD risk loci to a multiancestral population. Our cohort is comparable to prior studies of mood in cSLE as we found a significant association between NPSLE and depression. Future work will examine anxiety.

Effects of neuroticism on suicide risk in major depressive disorder and bipolar disorder

BackgroundSuicide is the primary cause of death in patients with major depressive disorder (MDD) or bipolar disorder (BD). Among various personality traits, neuroticism is particularly relevant to suicide risk. However, its role in MDD and BD has not been examined sufficiently. This study characterized neuroticism in patients with MDD or BD, and analyzed the association between neuroticism and suicide risk in these patients.MethodsThis study collected demographic information and personality traits of MDD and BD patients. Group differences were assessed using t-tests, chi-square tests, and Mann-Whitney U tests. To identify factors associated with suicide risk, correlation analysis was first conducted, followed by bivariate and generalized ordered logistic regression for significant variables, including neuroticism. Sensitivity analyses were performed by progressively excluding potential confounders to evaluate the robustness of neuroticism’s effect. Additionally, simple mediation analyses using a bootstrap approach were conducted to examine whether depressive symptoms mediated the association between neuroticism and suicide risk in MDD and BD separately. A two-tailed P < 0.05 was considered statistically significant.ResultsThe study population comprised 88 MDD patients and 90 BD patients. Lifetime suicide risk was present in 39.3% of the study population. In the entire sample, neuroticism was significantly associated with both lifetime (r = 0.18, P = 0.018) and current suicide risk (r = 0.17, P = 0.024). In patients with MDD, through mediation analysis, neuroticism predicted both depressive symptom severity (B = 0.25, P < 0.001) and current suicide risk (B = 0.02, P = 0.022), while also indirectly influencing current suicide risk through depressive symptoms (B = 0.01, 95% CI = 0.01–0.02). In BD patients, neuroticism predicted depressive symptoms (B = 0.13, P = 0.002) but not current suicide risk (B < 0.01, P = 0.714), while depressive symptoms fully mediated this relationship (B = 0.06, P < 0.001).ConclusionNeuroticism plays a significant role in influencing suicide risk among MDD and BD, through its effect on depressive symptoms. Interventions for neuroticism can reduce depressive symptoms and suicide risk. This highlights the necessity of identification and management of neuroticism in suicide prevention strategies.

Protective Role of Regular Physical Activity on Mental Health During the COVID-19 Pandemic.

Understanding the impacts of lifestyle on mental health has become crucial. This study analyzed whether regular physical activity influences mental health indicators related to major depressive disorder, generalized anxiety, and COVID-19-related anxiety and obsession among Brazilian adults during the pandemic. Additionally, social adjustment and health and disability were assessed to measure broader impacts of physical activity on daily functioning and quality of life during the COVID-19 pandemic, an anxiogenic period. Participants completed sociodemographic, physical activity, and clinical surveys, along with standardized mental health scales: the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), the Brazilian version of the Coronavirus Anxiety Scale (CAS-BR), the COVID-19 Obsession Scale (PB-OCS), the Work and Social Adjustment Scale (WSAS), and the WHO Disability Assessment Schedule (WHODAS 2.0). Descriptive analysis characterized the sample, while univariate, bivariate, and multivariate analyses of variance were conducted to explore the influence of physical activity and sex on mental health outcomes. The results indicated that women exhibited poorer mental health outcomes than men across most measures. Engaging in regular physical activity significantly reduced the risk of major depressive disorder in both women and men. Additionally, physically active women-but not men-had a lower likelihood of generalized anxiety and social adjustment impairments. Furthermore, individuals with longer engagement in physical activity (> 5 years) experienced greater mental health benefits compared to those with shorter engagement (< 5 years), particularly for depressive symptoms and generalized anxiety. This study highlights the protective effects of regular physical activity on mental health, with sex-specific differences in its impact. Long-term engagement in physical activity provides greater mental health benefits, reinforcing the importance of promoting sustained participation rather than short-term engagement.

Association of PBRM1 rs2251219 with major depressive disorder and biochemical variables in a Taiwanese cohort.

Association of PBRM1 rs2251219 with major depressive disorder and biochemical variables in a Taiwanese cohort.

Optimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans

Objectives Major depressive disorder (MDD) is a leading cause of disability, and chronic inflammation is a contributing factor to its onset and progression. This study examined the relationship between genetic predisposition to inflammation and MDD risk in a nationally representative sample of U.S. military veterans, as well as psychosocial moderators of this association. Methods A composite polygenic risk score (PRS) for inflammatory biomarkers was derived from the UK Biobank and examined in relation to a positive MDD screen in 1,660 European-American veterans. The analysis adjusted for known correlates of inflammation and MDD, including medical conditions and cumulative trauma burden. Results Each standard deviation increase in the inflammatory PRS was associated with more than two-fold increased odds of screening positive for MDD (OR = 2.51, 95% CI = 1.39–4.54). Interaction analyses revealed that optimism moderated this association; among those in the highest PRS tertile, individuals with high optimism were more than 30 times less likely to screen positive for MDD compared to those with low optimism (0.7% vs. 22.6%). Pathway-based analyses identified enrichment of immune- and brain-related gene sets, highlighting potential biological mechanisms linking inflammation and MDD. Conclusions Findings suggest genetic risk for inflammation contributes to MDD vulnerability and that optimism may buffer this risk.

Separating the effects of childhood and adult obesity on depression, subjective well-being, and suicide attempt: a Mendelian randomization study.

Observational studies have linked obesity, both in childhood and adulthood, with higher risks of depression, reduced subjective well-being (SWB), and suicide attempts (SA). However, the causality remains unclear. This study aimed to investigate the causal effects of childhood and adult obesity on depression, SWB, and SA. A bidirectional two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data to examine the causal effects of body mass index (BMI) on depression, SWB, and SA. The inverse variance weighted method was used for primary analysis. Univariable and multivariable MR were employed to assess the total and independent effects of early life and adult body size. Cochran's Q test and MR-Egger intercept were applied to evaluate heterogeneity and pleiotropy. Genetically predicted BMI was significantly associated with an increased risk of major depressive disorder (MDD: OR = 1.13, 95%CI = 1.06-1.22, p = 6.1 × 10⁻⁴), SA-ISGC (OR = 1.17, 95%CI = 1.08-1.27, p = 1.9 × 10⁻⁴), and SA-iPSYCH (OR = 1.31, 95%CI = 1.12-1.54, p = 6.2 × 10⁻⁴). No significant causal effects of MDD, SWB, or SA on BMI were found. Early-life body size showed no direct effect on MDD or SA. However, adult body size was directly linked to increased risks of MDD (OR = 1.32, 95%CI = 1.13-1.55, p = 4.7 × 10⁻⁴), SA-ISGC (OR = 1.24, 95%CI = 1.03-1.47, p = 0.022), and SA-iPSYCH (OR = 1.80, 95%CI = 1.29-2.50, p = 5.6 × 10⁻⁴). This study provides robust evidence supporting a causal link between obesity and an increased risk of both depression and SA, with adult body size exerting a more direct impact on these outcomes than early-life body size.

Self-reported and actimetry-based cluster analysis of mood rhythmicity profiles in adolescents with and at risk for Major Depressive Disorder

ABSTRACT Greater self-perceived rhythmicity of mood-related symptoms and behaviors has been associated with depressive symptoms in the general public. We aimed to evaluate differences in adolescents at risk for or with a diagnosis of major depressive disorder (MDD) regarding perception of symptom rhythmicity and actimetry parameters. In this cross-sectional study, 96 adolescents were stratified into three groups based on either a diagnosis of MDD or on a composite score for the risk of developing depression: MDD, high risk (HR), and low risk (LR). Participants completed questionnaires regarding depressive symptoms (Mood and Feelings Questionnaire for adolescents) and self-perceived mood rhythmicity (Mood Rhythm Instrument for Youth – MRhI-Y). Actimetry data were collected for 10 continuous days and Non-Parametric Circadian Rhythm Analyses were performed. The MDD group reported higher MRhI-Y total scores, particularly in affective symptoms compared to both other groups. In spite of actimetry variables that did not correlate with MRhI-Y total scores, cluster analysis using MRhI-Y and actimetry revealed three distinct profiles corresponding to all groups. Identifying rhythmicity in mood-related behaviors in adolescents may help distinguish different groups at-risk for MDD and in a current depressive episode. Understanding these patterns could inform early interventions, potentially preventing the onset of the disorder in susceptible individuals.