Peer Social Genetic Effects and the Etiology of Substance Use Disorders, Major Depression, and Anxiety Disorder in a Swedish National Sample.

OBJECTIVE: There is growing interest in how peers' genotypes may influence health (i.e., peer social genetic effects). The authors sought to clarify the nature of peer social genetic effects on risk for drug use disorder, alcohol use disorder (AUD), major depression, and anxiety disorder. METHOD: Cox models were used with data from a population-based Swedish cohort (N=655,327). Outcomes were drug use disorder, AUD, major depression, and anxiety disorder registrations between ages 17 and 30 from medical, criminal, and pharmacy registries. The authors indexed peer social genetic effects with peers' family genetic risk scores (FGRSs) for the same disorders, which are personalized measures of genetic risk inferred from diagnoses in first- to fifth-degree relatives. RESULTS: Across disorders, peer FGRSs predicted increased risks of proband registration (hazard ratio range, 1.01-1.59), with stronger effects for drug use disorder and AUD than for major depression and anxiety disorder. Peer social genetic effects were stronger for school classmates than for geographically proximal peers, and for peers from upper secondary school (ages 16-19) versus peers from lower secondary school (ages 7-16). Peer social genetic effects remained significant following statistical control for sociodemographic confounders, whether peers were affected, and peers' FGRS for educational attainment. Peer social genetic effects were more pronounced for probands at higher genetic risk. CONCLUSIONS: The genetic makeup of adolescents' peers has long-reaching consequences on risks for drug use disorder, AUD, major depression, and anxiety disorder. Individuals at high genetic risk are more sensitive to social genetic effects. Alternative hypotheses such as sociodemographic stratification, exposure to affected peers, and genetic predispositions for educational attainment did not explain the risk associated with peer social genetic effects for substance use and psychiatric disorders.

Stress-Related Roles of Exosomes and Exosomal miRNAs in Common Neuropsychiatric Disorders.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act both as cytoplasmic post-transcriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the central nervous system (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes in exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

Clinical Outcomes of Electroconvulsive Therapy (ECT) for Depression in Older Old People Relative to Other Age Groups Across the Adult Life Span: A CARE Network Study.

INTERVENTION: Electroconvulsive therapy (ECT) is a commonly used treatment for severe psychiatric illness in older adults, including in the 'older old' population aged 80 years and above. However, there can sometimes be a reluctance to treat the 80+ year old age group with ECT due to medical comorbidities, frailty, and concerns about cognition. OBJECTIVE, DESIGN, SETTING, AND PARTICIPANTS: This multi-site, longitudinal Australian study aimed to investigate the effectiveness and safety of ECT in older old people compared with younger age groups. Data from 310 people receiving ECT for depression at three participating hospitals was collected in a naturalistic setting, between 2015 and 2022. MEASUREMENTS: Clinical ratings were conducted pre-ECT and end-acute ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Older old adults demonstrated a significant reduction MADRS scores at post-treatment. They were more likely to meet remission criteria compared with the younger age groups. Older old adults were also less likely to show clinically significant cognitive decline post-ECT, and were more likely to show clinically significant cognitive improvement post-ECT compared with younger age groups. CONCLUSIONS: ECT is highly effective in treating severe psychiatric illness in older old adults. Relative to the younger age groups, the older old group were more likely to remit with ECT and a greater proportion showed cognitive improvement post-ECT. These findings suggest that ECT should be considered as a valuable and safe treatment option for older old individuals with depression.

Regional gray matter changes in steatotic liver disease provide a neurobiological link to depression: A cross-sectional UK Biobank cohort study.

BACKGROUND: Steatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD. To investigate a possible shared neurobiology with depression, we examined liver fat-related regional gray matter alterations in SLD and its most significant clinical subgroup metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We analyzed regional cortical thickness and area obtained from brain MRI in 29,051 participants in UK Biobank. Liver fat amount was computed as proton density fat fraction (PDFF) from liver MRI scans. We examined the relationship between brain structure and PDFF, adjusting for sociodemographic, physical, lifestyle, and environmental factors, as well as alcohol intake and a spectrum of cardiometabolic covariates. Finally, we compared patterns of brain alterations in SLD/MASLD and major depressive disorder (MDD) using previously published results. RESULTS: PDFF-related gray matter alterations were region-specific, involving both increases and decreases in cortical thickness, and increased cortical area. In several regions, PDFF effects on gray matter could also be attributed to cardiometabolic covariates. However, PDFF was consistently associated with lower cortical thickness in middle and superior temporal regions and higher cortical thickness in pericalcarine and right frontal pole regions. PDFF-related alterations for the SLD and the MASLD group correlated with those observed in MDD (Pearson r = 0.45-0.54, p < 0.01). CONCLUSION: These findings suggest the presence of shared biological mechanisms linking MDD to SLD and MASLD. They might explain the well-known elevated risk of depression in these groups and support early lifestyle interventions and treatment of metabolic risk factors for the successful management of the interconnected diseases depression and SLD/MASLD.

Combinatorial therapy with sub-effective Ro25-6981 and ZL006 ameliorates depressive-like behavior in single or combined stressed male mice.

Major depression is a severe neuropsychiatric disorder that poses a significant challenge to health. However, development of an effective therapy for the disease has long been difficult. Here, we investigate the efficacy of a novel combinatorial treatment employing sub-effective doses of Ro25-6981, an antagonist targeting GluN2B-containing NMDA receptors, in conjunction with ZL006, an inhibitor of the PSD95/nNOS, on mouse models of depression. We employed social isolation, chronic restraint stress, or a combination of both to establish a depressed mouse model. Treatment with the drug combination reduced depressive-like behaviors without affecting locomotor activity in mice subjected to social isolation or chronic restraint stress. Furthermore, the combination therapy ameliorated depressive-like behaviors induced by combined stress of chronic restraint followed by social isolation. Mechanistic studies revealed that the combined treatment downregulated the hippocampal nitric oxide level. However, the therapeutic benefits of this combination were negated by the activation of NMDA receptors with a low dose of NMDA or by increasing nitric oxide levels with l-arginine. Moreover, the combinatorial treatment had negligible effects on object memory and contextual fear memory. Our data establish a combined therapy paradigm, providing a potential strategy targeting major depression.

Mood Disorders in the Wake of Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI) frequently leads to a myriad of long-term consequences, among which mood disorders present a significant challenge. This systematic review delves into the complex interplay between TBI and subsequent mood disorders, focusing on research studies conducted over the past decade. Encompassing an age range from 12 years old to older adults (60+ years), our review aims to elucidate the epidemiological patterns, neurobiological mechanisms, and psychosocial factors that contribute to the development of mood disorders following TBI. By synthesizing the current literature, we seek to uncover the prevalence and clinical implications of this often-under-recognized comorbidity. For the quality appraisal of the reviewed articles, the Newcastle-Ottawa risk-of-bias tool and Scale for the Assessment of Narrative Review Articles (SANRA) checklist were employed. Ultimately, this review endeavors to provide a comprehensive understanding of the intricate relationship between TBI and mood disorders, offering insights crucial for improved management and intervention strategies in affected individuals.

A randomised, open-label, pragmatic pilot comparison of oral and intravenous ketamine in treatment-resistant depression.

BACKGROUND: For depression, ketamine is more conveniently administered by oral than by intravenous (iv) routes. The relative antidepressant efficacy of oral vs iv ketamine is unknown. OBJECTIVES: To assess the acute efficacy and the persistence of improvement with open-label oral versus iv ketamine in outpatients with treatment-resistant depression (TRD). METHODS: Adults with TRD were randomized to oral (N=30) or IV (N=31) ketamine. Oral ketamine was dosed at 150 mg in 50 mL of water, sipped across 15 min. IV ketamine was dosed at 0.5 mg/kg, infused across 40 min. Ketamine sessions (total, 7) were administered on alternate days for 2 weeks. Ongoing antidepressant drugs were continued unchanged. Patients were assessed at baseline, day 14, and day 30. The primary outcome was the endpoint Hamilton Rating Scale for Depression score on day 14. Secondary outcomes were endpoint scores on the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impression-Severity of Illness and Improvement. RESULTS: Overall dropout was lower with oral than with iv ketamine (26.7 % vs 54.8 %; P=0.03). The 2 groups did not differ in depression ratings and in response and remission rates on all instruments on both days 14 and 30. Adverse events such as headache (56.7 % vs 74.2 %) and drowsiness (0.0 % vs 22.6 %) were less common with oral ketamine. CONCLUSION: In TRD outpatients treated in general hospitals, oral ketamine maybe better accepted and tolerated than iv ketamine. Conclusions about relative efficacy cannot be drawn because of the high dropout rate with iv ketamine.

Butyrate- and Beta-Hydroxybutyrate-Mediated Effects of Interventions with Pro- and Prebiotics, Fasting, and Caloric Restrictions on Depression: A Systematic Review and Meta-Analysis.

To examine the butyrate- and beta-hydroxybutyrate (BHB)-modulated effects of pre- and probiotic interventions, fasting, and caloric restriction interventions, a systematic literature review was carried out with a subsequent meta-analysis. Three pre-and probiotic intervention randomized control trials (RCTs) were included in the meta-analysis. A significant increase in butyrate (standardized mean difference (SMD) [confidence interval (CI)] 0.34; [0.02-0.67]) and an improvement in depression scores (SMD [CI] 0.15, [-0.35-0.70]) through pre- and probiotic interventions were shown in the meta-analysis. The intervention duration of the included studies ranged from three days to four weeks, with the examined population being healthy adults. Butyrate was measured in either plasma or feces, and the depression score was obtained under the Swedish core affect scale, the hospital anxiety and depression scale (HADS), or the depression, anxiety, and stress scale-21 items (DASS-21). In addition to butyrate, the total SCFA concentration also seems to be positively associated with pre- and probiotic administration (SMD [CI] 0.55 [0.15-0.95]). Despite the significant short-chain fatty acid (SCFA) and butyrate concentration changes, no significant correlation between butyrate and depression or between SCFAs and depression could be shown through linear regression models. Nevertheless, the regression coefficient b1 = 1.57 (p = 0.17) for butyrate suggests a strong, positive connection between butyrate and depression. Additionally, three studies were qualitatively analyzed, examining fasting as an intervention and revealing a connection between fasting, BHB, and depression. The association between fasting, BHB, and depression or mood elevation appeared to be related to BHB concentrations, which may be due to the similar biochemical properties of BHB and butyrate. Furthermore, caloric restrictions as alternatives to fasting were proposed as potential long-term interventions.

Borderline personality features in relationship to childhood trauma in unipolar depressive and bipolar disorders.

BACKGROUND: Childhood trauma, including emotional neglect, emotional abuse, physical abuse, and sexual abuse, may contribute to borderline personality features like affective instability, identity problems, negative relationships, and self-harm. This study aims to explore how different types of childhood trauma affect these features in bipolar versus unipolar depressive disorders. METHODS: We included 839 participants of the Netherlands Study of Depression and Anxiety (NESDA) with a lifetime diagnosis of major depressive disorder single episode (MDDS; N = 443), recurrent major depressive disorder (MDD-R; N = 331), or bipolar disorder (BD; N = 65). Multivariate regression was used to analyze data from the Childhood Trauma Interview and borderline features (from the self-report Personality Assessment Inventory). RESULTS: On average, participants were 48.6 years old (SD: 12.6), with 69.2 % being women, and 50.3 % of participants assessed positive for childhood trauma. Adjusted analyses revealed that participants diagnosed with BD, followed by MDD-R, exhibited the highest number of borderline personality features. Additionally, within the entire group, a strong association was found between childhood trauma, especially emotional neglect, and the presence of borderline personality features. CONCLUSION: Given the high prevalence of childhood trauma and borderline personality features, screening for these factors in individuals with mood disorders is crucial. Identifying these elements can inform and enhance the management of the often fluctuating and complex nature of these comorbid conditions, leading to more effective and tailored treatment strategies.

Association between serum Klotho and major depression: Results from the NHANES 2007-2016 and Mendelian randomization studies.

BACKGROUND: Major depression is a public health problem facing the world. This study aimed to identify the risk factors for major depression and clarify their causal effects. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression analysis was used to calculate the effect of each variable on major depression. Subgroup analyses and interaction tests were conducted to observe the stability of the association between them. Nonlinear correlations were explored using restricted cubic spline plots. The causal effects of serum Klotho on major depression were assessed using Mendelian randomization (MR) analysis. RESULTS: A total of 8359 participated in the study. After adjusting for all covariates, the risk of having major depression was 1.47 times higher for each unit rise in serum Klotho (OR = 1.47, 95 % CI = 1.07-2.02; P = 0.0183). MR analysis showed no causal relationship between serum Klotho levels and risk of major depression (OR = 1.09, 95 % CI = 0.91-1.30; P = 0.4120). Sensitivity analysis verified the reliability of the results. CONCLUSIONS: Serum Klotho is positively associated with an increased risk of major depression in the U.S. population, but MR analyses did not show genetic causality between Klotho and major depression in individuals of European ancestry. Based on the results of the current study, no indication maintaining high levels of Klotho may increase the risk of major depression. LIMITATIONS: The main limitation of this study is the inconsistency of the cross-sectional study and the MR population.

Improving Mental Health Outcomes in Patients with Major Depressive Disorder in the Gulf States: A Review of the Role of Electronic Enablers in Monitoring Residual Symptoms.

Up to 75% of individuals with major depressive disorder (MDD) may have residual symptoms such as amotivation or anhedonia, which prevent full functional recovery and are associated with relapse. Globally and in the Gulf region, primary care physicians (PCPs) have an important role in alleviating stigma and in identifying and monitoring the residual symptoms of depression, as PCPs are the preliminary interface between patients and specialists in the collaborative care model. Therefore, mental healthcare upskilling programmes for PCPs are needed, as are basic instruments to evaluate residual symptoms swiftly and accurately in primary care. Currently, few if any electronic enablers have been designed to specifically monitor residual symptoms in patients with MDD. The objectives of this review are to highlight how accurate evaluation of residual symptoms with an easy-to-use electronic enabler in primary care may improve functional recovery and overall mental health outcomes, and how such an enabler may guide pharmacotherapy selection and positively impact the patient journey. Here, we show the potential advantages of electronic enablers in primary care, which include the possibility for a deeper "dive" into the patient journey and facilitation of treatment optimisation. At the policy and practice levels, electronic enablers endorsed by government agencies and local psychiatric associations may receive greater PCP attention and backing, improve patient involvement in shared clinical decision-making, and help to reduce the general stigma around mental health disorders. In the Gulf region, an easy-to-use electronic enabler in primary care, incorporating aspects of the Hamilton Depression Rating Scale to monitor amotivation, and aspects of the Montgomery-Åsberg Depression Rating Scale to monitor anhedonia, could markedly improve the patient journey from residual symptoms through to full functional recovery in individuals with MDD.

The alterations in CD4+Treg cells across various phases of major depression.

BACKGROUND: Major depression (MD) is recurrent and devastating mental disease with a high worldwide prevalence. Mounting evidence suggests neuroinflammation triggers cellular immune dysregulation, characterized by increased proportions of circulating monocytes, and T helper 17 cells and proinflammatory cytokines, thereby increasing susceptibility to MD. However, there is ambiguity in the findings of clinical studies that investigate CD4+ T regulatory (Treg) cells in MD. METHODS: The proportion of CD4+ Treg cell from blood mononuclear cells was examined using flow cytometry in healthy controls (HCs: n = 96) and patients with first (FEMD: n = 62) or recurrent (RMD: n = 41) disease episodes of MD at baseline (T0; hospital admission) and after a two-week antidepressant treatment (T14). All participants underwent comprehensive neuropsychological assessments. RESULTS: The initial scores on emotional assessments in patients with MD significantly differed from those of HCs. Both FEMD and RMD patients exhibited a significant decrease in CD4+ Treg cell proportion at baseline compared to HCs. Treg cell proportion rose significantly from T0 to T14 in FEMD patients, who responded to antidepressant therapy, whereas no significant changes were observed in FEMD patients in non-response as well as RMD patients. The improvement of 24-item Hamilton Depression Scale was correlate with changes of Treg cell proportion from T0 to T14 in FEMD patients in response, and the change in Treg cell proportion over a 14-day period exhibited an AUC curve of 0.710. CONCLUSIONS: A decrease in the proportion of CD4+ Treg cells points towards immune system abnormalities in patients with MD. Furthermore, our finding suggests that the immune activation state varies across different stages of depression.

Bidirectionality of LF when the movie makes you sad: Effects of negative emotions on heart rate variability among patients with major depression.

OBJECTIVES: Heart rate variability (HRV) reflects the capacity to adapt to internal and environmental changes. Decreased HRV may indicate inadequate adaptive capacity. This study aims to investigate the relationship between the heart and brain's adaptive abilities, both at rest and when negative emotions are stimulated in depression. SUBJECTS AND METHODS: The study included 30 patients (20 female, 10 male) with major depression (mean age = 29.8 ± 7.8) and 30 healthy controls, all of whom had similar characteristics in terms of age and gender, selected through convenience sampling. The patients were drug-free at the time of the assessment. Holter recordings were obtained while subjects watched videos stimulating anger, fear, sadness, and a neutral video, and at rest, HRV parameters were calculated. To control for interindividual variability and account for paired sampling, linear mixed effects models were employed. RESULTS: Watching the 'sadness video' led to an increase in low frequency band (LF) [LF change (Control vs depression); Difference:-620.80 df:107 t:-2.093 P:0.039] and LF/high frequency band ratio (LF/HF) [LF/HF change (control vs depression group); Difference:-1.718 df:105 t:-2.374 P:0.020] in the depression group. The video led to a decrease in LF and LF/HF in the controls. Although the differences between the conditions and interactions with the group were significant, the effects were independent of depression severity. CONCLUSION: In depression, brain's regulatory effect on the heart differed from controls in the sadness condition, possibly due to increased arousal levels in subjects with depression and their inability to suppress sympathetic activity when a state of sadness is stimulated.

TanhReLU -based convolutional neural networks for MDD classification.

Major Depression Disorder (MDD), a complex mental health disorder, poses significant challenges in accurate diagnosis. In addressing the issue of gradient vanishing in the classification of MDD using current data-driven electroencephalogram (EEG) data, this study introduces a TanhReLU-based Convolutional Neural Network (CNN). By integrating the TanhReLU activation function, which combines the characteristics of the hyperbolic tangent (Tanh) and rectified linear unit (ReLU) activations, the model aims to improve performance in identifying patterns associated with MDD while alleviating the issue of model overfitting and gradient vanishing. Experimental results demonstrate promising outcomes in the task of MDD classification upon the publicly available EEG data, suggesting potential clinical applications.

Can the DEX/CRH test or markers of oxidative stress distinguish work-related stress from major depressive disorder and normal controls?

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested.

The impact of family-genetic risk scores on social functioning in individuals affected with six major psychiatric and substance use disorders in a Swedish National Sample.

To examine whether the level of genetic risk in psychiatric disorders impacts the social functioning of affected individuals, we examine the relationship between genetic risk factors for major depression (MD), anxiety disorders (AD), bipolar disorder (BD), non-affective psychosis (NAP), alcohol use disorder (AUD), and drug use disorder (DUD) in disordered individuals and five adverse social outcomes: unemployment, residence in areas of social deprivation, social welfare, early retirement, and divorce. We examine all cases with registration for these disorders from 1995 to 2015 in individuals born in Sweden. Genetic risk was assessed by the family genetic risk score (FGRS) and statistical estimates by Cox proportional hazard models. High genetic risk was significantly and modestly associated with poorer social outcomes in 23 of 30 analyses. Overall, genetic risk for MD, AD, AUD, and DUD impacted social functioning more strongly in affected individuals than did genetic risk for BD and NAP. Social welfare had the strongest associations with genetic risk, and residence in areas of high deprivation had the weakest. In individuals suffering from psychiatric and substance use disorders, high levels of genetic risk impact not only clinical features but also diverse measures of social functioning.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis.

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy. Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study. Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38). Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.

Impact of subjective sleep quality on objective measures of neurocognitive dysfunction in patients with major depressive disorder.

Background: Sleep disturbances are prevalent in major depressive disorder (MDD). MDD and sleep disturbances are both linked to cognitive impairments. Studies exploring the mechanisms and impact of sleep disturbances on neurocognitive functioning in depressed patients are lacking and proper assessment and therapeutic interventions for sleep disturbances are not part of clinical management of MDD. Aim: We investigated the association between subjective sleep quality and neurocognitive dysfunction in patients with MDD. Materials and Methods: Patients with moderate MDD episode were matched and assigned to two groups with poor and good sleep quality. We used Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. To measure frontotemporally mediated cognitive functioning, following tests were administered: Wisconsin Card Sorting Test (WCST) and degraded continuous performance test (CPT-DS). Two-tailed independent samples t tests or Mann-Whitney U tests and Pearson's correlation coefficient were performed for the statistical analysis of sleep latency, sleep duration, overall sleep quality, CPT d' value, WCST correct answers, errors, and perseverative errors. Results: Participants with MDD and poor sleep quality performed worse on cognitive tests compared to patients with MDD and good sleep quality. Scores of subjective sleep on PSQI positively correlated with WCST errors (r (60) =0.8883 P = .001) and negatively correlated with WCST correct answers (r (60) = -.869 P = .001) and measures of CPT-DS d' value (r (60) = -.9355 P = .001). Conclusions: Poor sleep quality, notably sleep duration and sleep latency, worsens the neurocognitive impairments of MDD patients. As these impairments are found to be associated with treatment outcomes, sleep disturbances should be additionally assessed and treated in MDD episode.