Risk Of Major Depressive Disorder Research Articles

Estradiol effects on an emotional interference task in adolescents with current and remitted depression

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.

Abnormal spontaneous activity of regions related to mood regulation mediates the effect of childhood emotional neglect on major depressive disorder

This study investigated the mediating factors between childhood emotional neglect (EN) and major depressive disorder (MDD) and whether combining multi-indicator could help diagnose MDD. Regional homogeneity (ReHo) and clinical features were compared between 33 MDD patients and 36 healthy controls (HC). Mediation analysis was employed to explore whether social support or ReHo mediates the association between EN and MDD. The linear discriminant analysis model was constructed with EN, social support, and ReHo, and applied to distinguish MDD from HC in both primary and replication cohorts. We found that MDD patients experienced severer EN and poorer social support, and exhibited lower ReHo in the left middle occipital gyrus and bilateral postcentral gyrus, and higher ReHo in the right cerebellum crus1. EN could affect MDD directly and indirectly through ReHo in these discrepant brain regions and social support. Combining ReHo values of these four distinct brain regions, EN, and objective support could classify MDD patients from HC, and the 10-fold cross-validation accuracy within-study replication and in the independent cohort was 83.78 % ± 1.49 % and 82.72 % ± 2.22 %, respectively. These findings suggested that childhood EN, social support, and emotional-related regions’ ReHo were associated with risks of MDD, providing new insights into the pathological mechanisms underlying MDD.

Heightened neural activity and functional connectivity responses to social rejection in female adolescents at risk for depression: Testing the Social Signal Transduction Theory of Depression

BackgroundAlthough social rejection is among the strongest proximal precipitants of major depressive disorder (MDD), little is known about the underlying neurobiological mechanisms and whether neural sensitivity to social rejection may help explain differences in MDD risk. To address this issue, we tested whether neural responses to social threat differed in female adolescents at high vs. low maternal risk for MDD. MethodFemale adolescents with (high-risk; n = 22, Mage = 14.68) and without (low-risk; n = 30, Mage = 15.07) a maternal history of depression were experimentally exposed to negative and neutral social evaluation while undergoing an fMRI scan. Neural responses were assessed by event-related activity and functional connectivity, as well as multivoxel pattern analysis. Activity and functional connectivity analyses focused on a priori-selected regions of interest implicated in self-referential processing and emotion regulation. ResultsCompared to low-risk female adolescents, high-risk female adolescents exhibited greater increases in self-reported depression and social disconnection following social evaluation. Moreover, compared to low-risk female adolescents, high-risk female adolescents exhibited greater amygdala responses to negative social evaluation and a differential pattern of functional connectivity in brain regions related to emotion regulation, self-referential processing, and negative affect. Additionally, these markers of neural threat reactivity were related to depressive symptoms. LimitationsA cross-sectional study design and relatively small, Western sample. ConclusionsThese results suggest that exaggerated neural reactivity to social threat—and an atypical pattern of related functional connectivity—is evident in individuals with a preclinical risk factor for depression. Targeting such responding may thus be a fruitful strategy for preventing depression in at-risk youth.

Causality between sarcopenia-related traits and major depressive disorder: A bi-directional, two-sample Mendelian randomized study.

Observational studies have demonstrated an association between sarcopenia and depression. However, these studies may be influenced by confounding factors, and the causal relationship between sarcopenia and major depressive disorder (MDD) remains unclear. This study aimed to apply the Mendelian randomization (MR) method to address confounding factors and assess the causal effect of sarcopenia on MDD. A two-way, two-sample MR method was employed in this study. Instrumental variables of genome-wide significance level were obtained from the open large-scale genome-wide association study summary data. MR analysis was conducted using inverse variance weighted, MR-Egger, and weighted median methods. The reliability of the results was verified using the heterogeneity test, pleiotropy test, and leave-one-out method for sensitivity analysis. Grip strength (right-hand grip strength: odds ratio [OR] = 0.880, 95% confidence interval [CI] 0.786-0.987, P = .027; left-hand grip strength: OR = 0.814, 95% CI 0.725-0.913, P < .001) and usual walking pace (OR = 0.673, 95% CI 0.506-0.896, P = .007) exhibited a direct causal effect on MDD. MDD had a significant causal effect on appendicular lean mass (β = -0.065, 95% CI -0.110, -0.019, P = .005). There was a causal relationship between sarcopenia-related traits and MDD. Loss of muscle strength, rather than skeletal muscle mass, is correlated with an increased risk of MDD. Furthermore, individuals with MDD are more likely to experience loss of skeletal muscle mass.

Sequential autoencoders for feature engineering and pretraining in major depressive disorder risk prediction.

We evaluated autoencoders as a feature engineering and pretraining technique to improve major depressive disorder (MDD) prognostic risk prediction. Autoencoders can represent temporal feature relationships not identified by aggregate features. The predictive performance of autoencoders of multiple sequential structures was evaluated as feature engineering and pretraining strategies on an array of prediction tasks and compared to a restricted Boltzmann machine (RBM) and random forests as a benchmark. We study MDD patients from Vanderbilt University Medical Center. Autoencoder models with Attention and long-short-term memory (LSTM) layers were trained to create latent representations of the input data. Predictive performance was evaluated temporally by fitting random forest models to predict future outcomes with engineered features as input and using autoencoder weights to initialize neural network layers. We evaluated area under the precision-recall curve (AUPRC) trends and variation over the study population's treatment course. The pretrained LSTM model improved predictive performance over pretrained Attention models and benchmarks in 3 of 4 outcomes including self-harm/suicide attempt (AUPRCs, LSTM pretrained = 0.012, Attention pretrained = 0.010, RBM = 0.009, random forest = 0.005). The use of autoencoders for feature engineering had varied results, with benchmarks outperforming LSTM and Attention encodings on the self-harm/suicide attempt outcome (AUPRCs, LSTM encodings = 0.003, Attention encodings = 0.004, RBM = 0.009, random forest = 0.005). Improvement in prediction resulting from pretraining has the potential for increased clinical impact of MDD risk models. We did not find evidence that the use of temporal feature encodings was additive to predictive performance in the study population. This suggests that predictive information retained by model weights may be lost during encoding. LSTM pretrained model predictive performance is shown to be clinically useful and improves over state-of-the-art predictors in the MDD phenotype. LSTM model performance warrants consideration of use in future related studies. LSTM models with pretrained weights from autoencoders were able to outperform the benchmark and a pretrained Attention model. Future researchers developing risk models in MDD may benefit from the use of LSTM autoencoder pretrained weights.

Obesity and sarcopenic obesity characterized by low-grade inflammation are associated with increased risk for major depression in women.

We aimed to determine women's risk of major depressive disorder (MDD) in relation to obesity phenotypes characterized by levels of circulating high-sensitivity C-reactive protein (hsCRP). This population-based retrospective cohort study comprised 808 women (ages 20-84 y) recruited 1994-1997 and followed for a median 16.1 y (IQR 11.9-16.8). At baseline, body fat and lean tissue mass were measured by whole body dual-energy x-ray absorptiometry (DXA). Obesity was identified as high fat mass index (>12.9 kg/m2), body fat percentage (≥35%) and body mass index (≥30 kg/m2); sarcopenic obesity referred to a high ratio fat mass/fat-free mass (≥0.80). Systemic inflammation was operationalized as serum hsCRP concentration in the upper tertile (>2.99 mg/L). Obesity phenotypes were: non-obese + lowCRP, non-obese + highCRP, obese + lowCRP, and obese + highCRP. During follow-up, the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) was used to identify lifetime history of MDD and age of onset. Poisson regression models were used to estimate the MDD rate for each obesity phenotype during follow-up. Demographic, health and lifestyle factors were tested as potential confounders. During 11,869 p-y of follow-up, 161 (19.9%) women experienced an MDD episode. For obesity phenotypes based on fat mass index, models adjusted for baseline age and prior MDD, and non-obese + lowCRP as reference, RR for non-obese + highCRP was 1.21 (95% CI 0.80, 1.82), obese + lowCRP 1.46 (0.86, 2.47) and obese + highCRP 1.56 (1.03, 2.37). Patterns were similar for obesity by body fat percentage, body mass index and sarcopenic obesity. Consistently across different obesity definitions, this longitudinal study reports that women with both obesity and systemic inflammation are at increased risk of subsequent MDD. Future research should examine whether tackling this metabolically unhealthy obesity type - through, for example, lifestyle or medication approaches - can reduce depression risk.

Living in Proximity to Petrochemical Industrial Parks and Risk of Major Depression Disorder in Adults

Living in Proximity to Petrochemical Industrial Parks and Risk of Major Depression Disorder in Adults

The association between the Short Physical Performance Battery and longitudinal trajectories of depressive symptoms among Chinese older adults.

In this study, the long-term trajectories of depressive symptoms in a 7-year prospective survey cohort of Chinese older adults were explored. Additionally, the study examined whether there was an independent association between scores on the Short Physical Performance Battery (SPPB) and the different trajectories of depressive symptoms. A total of 2177 elderly individuals had their depressive symptoms assessed based on the Center for Epidemiological Studies-Depression (CES-D) scale in the years 2011, 2013, 2015, and 2018. In addition, their demographic characteristics, chronic diseases, and lifestyle factors were also assessed. The trajectories of depressive symptoms were analysed using the group-based trajectories analysis model. Furthermore, the relationship between the objectively measured SPPB scores and the long-term trajectory of depressive symptoms was explored using multinomial logistic regression. The group-based trajectory analysis model categorized the trajectories of depressive symptoms across four waves into four groups: persistent low depressive symptoms, increasing depressive symptoms, decreased depressive symptoms, and persistent high depressive symptoms. After controlling for confounding factors, it was observed that a higher baseline SPPB score was associated with an increased likelihood of persistent high depressive symptoms, OR (95% CI) = 0.724 (0.644, 0.814), for the persistent high depressive symptoms versus the persistent low depressive symptoms. Low levels of SPPB score are associated with persistent high depressive symptoms in older adults. Conversely, improving physical performance as measured by the SPPB can help reduce the risk of major depressive disorder and persistent depressive disorder in the elderly.

Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.

Association of psoriasis with depression, anxiety, and suicidality: A bidirectional two-sample Mendelian randomization study.

Psoriasis is a chronic, refractory inflammatory skin disease, with a high prevalence of psychiatric comorbidities, including depression, anxiety, and even suicidality, which may in turn initiate or exacerbate skin inflammation. However, the causal relationships between these comorbidities remain unclear. To investigate the cause-effect relationships between psoriasis and mental disorders including depression, anxiety, and suicidality, we conducted a bidirectional two-sample Mendelian randomization (MR) study utilizing summary statistics from the most comprehensive genome-wide association studies of psoriasis (n = 306 123), broad depression (n = 500 199), major depressive disorder (n = 173 005), anxiety (n = 17 310), and suicide attempts (n = 50 264). Using the random-effects inverse-variance weighted method as primary method, the forward MR analyses indicated that psoriasis was significantly associated with higher odds of broad depression (odds ratio [OR] 1.030, 95% confidence interval [CI] 1.010-1.051, P = 0.003) and suggestively associated with an increased risk of major depressive disorder (OR 1.054, 95% CI 1.002-1.109, P = 0.040), but not with the risk of anxiety (P = 0.160) or suicide attempts (P = 0.648). In reverse MR analyses, significant causal impact of broad depression (OR 1.363, 95% CI 1.103-1.684, P = 0.004) and major depressive disorder (OR 1.890, 95% CI 1.285-2.781, P = 0.001), but not anxiety (P = 0.787) and suicide attempts (P = 0.961) on psoriasis risk was observed. In addition, the results of primary analysis are consistent across sensitivity analyses, albeit the MR-Egger regression model produced wide CIs and negative results in several analyses. In conclusion, this MR study indicates a bidirectional causal relationship between psoriasis and depression that was previously unrecognized, which highlights the significance of screening for depression in psoriasis patients and initiating appropriate interventions. Further studies are required to elucidate the pathophysiology of the bidirectional causal relationship between these two conditions.

Mendelian randomization of the causal relationship between ω-3 polyunsaturated fatty acids and major depression

A two-sample Mendelian randomization method was used to explore the causal relationship between ω-3 polyunsaturated fatty acids and the risk of major depressive disorder. Using a large-scale genome-wide association study database, a series of quality control steps were taken to select qualified SNPs that were strongly associated with exposure. To make the conclusion more robust and reliable, inverse variance weighting, MR-Egger regression, weighted median, robustly adjusted profile scores, and pleiotropic residual and outlier tests were used based on different assumptions of two-sample Mendelian randomization five method for causal estimation. The causal relationship between ω-3 PUFA and the risk of MDD was studied with OR value and 95%CI as evaluation indicators. To assess horizontal pleiotropy, heterogeneity, and stability, MR-Egger intercept tests, Cochran&apos; Q and I~2 statistics, and "leave-one-out" sensitivity analyzes were performed. In addition, other datasets are used to check the result of the original dataset. A total of 66 SNP sites were included in the original data set as instrumental variables. The result of MR-PRESSO showed that there was no causal association between ω-3 PUFA and RA(OR=0.973, 95%CI 0.920-1.028, P=0.332). And the random effect IVW(OR=0.973, 95% CI 0.920-1.028, P=0.329), MR-Egger(OR=0.995, 95% CI 0.899-1.100, P=0.920), weighted median(OR=0.988, 95% CI 0.918-1.063, P=0.248) and MR-RAPS(OR=0.972, 95% CI 0.927-1.020, P=0.247) the causal estimation result of the four method tended to be consistent with the MR-PRESSO method, the result were robust. The validation set was consistent with the original data set in the estimation of the causal effect of ω-3 PUFA and MDD, and there was no causal relationship between the two. MR-Egger intercept test, original data set(intercept=-0.002, P=0.599) and validation set(intercept=0.012, P=0.628) indicated that the causal analysis result were less likely to be influenced by gene-level pleiotropy big. The result of two-sample Mendelian randomization analysis showed that there was no causal relationship between ω-3 PUFA and the risk of MDD.

Identifying the mediating role of socioeconomic status on the relationship between schizophrenia and major depressive disorder: a Mendelian randomisation analysis

Depressive disorder prevalence in patients with schizophrenia has been reported to be 40%. People with low socioeconomic status (SES) are more likely to suffer from schizophrenia and major depressive disorder (MDD). However, the causal relationship between schizophrenia and depression and the potential mediating role of SES remains unclear. Two-sample Mendelian randomization (MR) analyses were conducted to explore the bidirectional causal relationship between schizophrenia and MDD with the largest sample size of European ancestry from public genome-wide association studies (sample size ranged from 130,644 to 480,359). Inverse variance weighted (IVW) method was used as the primary analysis, and several canonical MR methods were used as validation analyses. The mediating role of SES (educational years, household income, employment status, and Townsend deprivation index) was estimated by the two-step MR method. MR analyses showed that genetically predicted schizophrenia was associated with an increased risk of MDD (IVW odds ratio [OR] = 1.137 [95% CI 1.095, 1.181]). Reversely, MDD was also associated with an increased risk of schizophrenia (IVW OR = 1.323 [95% CI 1.118, 1.565]). The mediation analysis via the two-step MR method revealed that the causal effect of schizophrenia on MDD was partly mediated by the Townsend deprivation index with a proportion of 10.27%, but no significant mediation effect was found of SES on the causal effect of MDD on schizophrenia. These results suggest a robust bidirectional causal effect between schizophrenia and MDD. Patients with schizophrenia could benefit from the early and effective intervention of the Townsend deprivation index.

BDNF rs962369 Is Associated with Major Depressive Disorder.

This study enrolled 291 patients diagnosed with depression and schizophrenia (F32, F33, and F20 according to ICD-10) and 227 ethnicity-matched control subjects. We analyzed the distribution of BDNF rs6265 and BDNF rs962369 genotypes, finding no significant associations between these and schizophrenia. We revealed a significant increase in the risk of single-episode major depression disorder (MDD) for rs962369 minor allele homozygotes (CC vs. TT+TC), an association that persisted after adjusting for age and sex (OR 3.47; 95% CI 1.36-8.85; p = 0.009). Furthermore, rs962369 genotype was significantly associated with an increased risk of recurrent MDD in a log-additive model (OR per C-allele 1.65; 95% CI 1.11-2.45; p = 0.013). A comparative analysis between MDD subtypes and between MDD subtypes and schizophrenia showed no significant differences for BDNF rs6265. Notably, the frequency of minor allele C of BDNF rs962369 varied across subgroups, with the highest frequency in patients with recurrent MDD (0.32) and the lowest in schizophrenia patients (0.20). The presence of genotypes with at least one minor allele C was significantly higher in the recurrent MDD patient group compared to the schizophrenia group. In conclusion, the BDNF rs962369 variant was associated with MDD but not with schizophrenia.

Genetic correlations between suicide attempts and psychiatric and intermediate phenotypes adjusting for mental disorders.

Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders. To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes. Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased. These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.

Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization

BackgroundCaffeine exposure modifies the turnover of monoamine neurotransmitters, which play a role in several neuropsychiatric disorders. We conducted a Mendelian randomization study to investigate whether higher plasma caffeine levels are causally associated with the risk of anorexia nervosa, bipolar disorder, major depressive disorder (MDD), and schizophrenia.MethodsSummary-level data on the neuropsychiatric disorders were obtained from large-scale genome-wide association studies (GWASs) of European ancestry participants (n = 72,517 to 807,553) and meta-analyzed with the corresponding data from the FinnGen study (n = 356,077). Summary-level data on plasma caffeine were extracted from a GWAS meta-analysis of 9876 European ancestry individuals. The Mendelian randomization analyses estimated the Wald ratio for each genetic variant and meta-analyzed the variant-specific estimates using multiplicative random effects meta-analysis.ResultsAfter correcting for multiple testing, genetically predicted higher plasma caffeine levels were associated with higher odds of anorexia nervosa (odds ratio [OR] = 1.124; 95% confidence interval [CI] = 1.024–1.238, pFDR = 0.039) and a lower odds of bipolar disorder (OR = 0.905, 95% CI = 0.827–0.929, pFDR = 0.041) and MDD (OR = 0.965, 95% CI = 0.937–0.995, pFDR = 0.039). Instrumented plasma caffeine levels were not associated with schizophrenia (OR = 0.986, 95% CI = 0.929–1.047, pFDR = 0.646).ConclusionsThese Mendelian randomization findings indicate that long-term higher plasma caffeine levels may lower the risk of bipolar disorder and MDD but increase the risk of anorexia nervosa. These results warrant further research to explore whether caffeine consumption, supplementation, or abstinence could render clinically relevant therapeutic or preventative psychiatric effects.

Genetically predicted circulating levels of cytokines and the risk of depression: a bidirectional Mendelian-randomization study.

Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis. Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) -18, IL-1β, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines. Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.

Modifiable risk factors of major depressive disorder: A Mendelian randomization study.

Identifying modifiable risk factors early on is essential to prevent major depressive disorder (MDD). This study systematically investigated the causal relationship between 19 modifiable risk factors and MDD. Single-nucleotide polymorphisms (SNPs) associated with 19 potentially modifiable risk factors were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for MDD (59,851 cases and 113,154 controls) were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. Genetically predicted smoking initiation increased the risk of MDD (P = 6.00E-09), while smoking status: never and past tobacco smoking decreased the risk of MDD (all P < 0.01). In addition, education level was inversely associated with MDD risk (all P < 0.01). Genetically instrumented sleeplessness/insomnia, daytime naps, and nap during the day were positively related to the risk of MDD (all P < 0.01). Personal feelings, including guilt, hurt, tension, and worry too long after an embarrassing experience, had a suggestive increased risk for MDD (all P < 0.000). The remaining five modifiable risk factors were all causally associated with the risk of MDD, including neuroticism, neuroticism scores, body mass index (BMI), average total household income before tax, and types of physical activity in the last 4 weeks (all P < 0.01). All 19 potentially modifiable risk factors were causally associated with the risk of MDD. The main hypothesis of this MR study was that identifying and intervening in these 19 potentially modifiable risk factors could be beneficial to the prevention and treatment of MDD and further reduce mortality and economic burden.

Mental Health Assessment and Risk Characterization in Puerto Rico’s Homeless Post-Hurricane Maria

ABSTRACT This study provides a mental health assessment of the homeless of Puerto Rico, compared to a non-homeless sample, in the aftermath of Hurricane Maria. Multi-stage sampling was used to assess risk of anxiety, depression, and PTSD, as well as provide a demographic profile of the homeless and non-homeless of Puerto Rico. The homeless, compared to non-homeless, had a significantly higher risk for all tested mental disorders. Pre-hurricane homeless had significantly higher risk for Major Depressive Disorder and severe mood and anxiety disorders compared to post. This study highlights the need for disaster preparedness strategies specific to this disproportionately affected population.

Evidence for a causal effect of major depressive disorder, anxiety on prostatitis risk: A univariate and multivariate Mendelian randomization study.

Observational studies have shown an association between major depressive disorder (MDD), anxiety, and prostatitis. However, the causal relationship between MDD, anxiety, and prostatitis remains controversial. Therefore, we aimed to use two-sample Mendelian randomization (MR) to assess the causal effects of MDD and anxiety on prostatitis. We conducted univariable and multivariable MR analyses using summary statistics from publicly available genome-wide association studies to estimate the causal relationships between MDD, anxiety, and prostatitis risk. In the main MR analysis, the inverse-variance weighted (IVW) method was used, while secondary methods included the weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual and outlier (MR-PRESSO) tests to detect and correct for the presence of pleiotropy. MDD had 97 independent instrumental variables (IVs) and anxiety had 15 IVs. Univariable MR analysis showed that genetically determined MDD had a detrimental causal effect on prostatitis (IVW: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.005), while no causal relationship was found between anxiety and prostatitis (IVW: OR = 0.25, 95% CI = 0.02-2.82, p = 0.26). More convincingly, after adjusting for confounding factors such as body mass index, alcohol consumption, and smoking, the genetic liability for MDD remained associated with prostatitis risk, with no strong evidence of anxiety affecting prostatitis incidence. This study supports the notion that MDD has a detrimental effect on prostatitis risk, and strategies focused on addressing MDD may be one of the cornerstones for treating prostatitis. The potential preventive value of treating MDD for prostatitis should be further investigated in future research.

Increased risk of depression in patients with discoid lupus erythematosus: a nested, case-control study in the All of Us Research Program.

In this nested case–control study, we found a twofold increased risk of major depressive disorder in patients with discoid lupus erythematosus (DLE) vs. controls without DLE, using the All of Us database, a National Institutes of Health (USA) research programme that prioritizes recruitment from demographic groups under-represented in biomedical research. This is the first large-scale study of this association in a heterogeneous population and highlights the importance vigilance regarding the increased risk of depression in patients with DLE.