Search

Major depression disorder (MDD) exhibits a high global incidence; however, its pathogenesis remains elusive. In this prospective study, we employed diffusion kurtosis imaging (DKI) to investigate changes in brain function among patients with MDD both pre- and post-electroconvulsive therapy (ECT). We divided a sample of 22 MDD patients into ECT group, which received six treatments over a span of two weeks, and control group (n = 12). DKI scanning was performed before and after treatment. The Hamilton Depression Rating Scale (HAMD) and Life Satisfaction Rating Scale (LSRS) were administered to assess depressive symptoms at baseline, on the 14th day, and at month three. Significant differences were found between group, time and time × group in terms of HAMD score and LSRS score. In the ECT group compared to pre- ECT measurement, changes in mean diffusivity (MD), fractional Anisotropy (FA), mean kurtosis (MK), radial kurtosis (RK), FA of kurtosis (KA), and anxia kurtosis (AK) value were detected in specific regions such as the frontal, temporal lobe, and hippocampus. In the control group only MD and RK value increased in a limited number of area. ECT holds the potential to elicit neuroplasticity in the brain, facilitating rapid structural modifications and amelioration of depressive symptoms in patients with MDD. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective in regulating mood and high-level cognition in patients with major depressive disorder (MDD). This study aimed to investigate the efficacy of taVNS treatment in patients with MDD and an altered brain topological organization of functional networks. Methods: Nineteen patients with MDD were enrolled in this study. Patients with MDD underwent 4 weeks of taVNS treatments; resting-state functional magnetic resonance imaging (rs-fMRI) data of the patients were collected before and after taVNS treatment. The graph theory method and network-based statistics (NBS) analysis were used to detect abnormal topological organizations of functional networks in patients with MDD before and after taVNS treatment. A correlation analysis was performed to characterize the relationship between altered network properties and neuropsychological scores. Results: After 4 weeks of taVNS treatment, patients with MDD had increased global efficiency and decreased characteristic path length (Lp). Additionally, patients with MDD exhibited increased nodal efficiency (NE) and degree centrality (DC) in the left angular gyrus. NBS results showed that patients with MDD exhibited reduced connectivity between default mode network (DMN)–frontoparietal network (FPN), DMN–cingulo-opercular network (CON), and FPN–CON. Furthermore, changes in Lp and DC were correlated with changes in Hamilton depression scores. Conclusions: These findings demonstrated that taVNS may be an effective method for reducing the severity of depressive symptoms in patients with MDD, mainly through modulating the brain's topological organization. Our study may offer insights into the underlying neural mechanism of taVNS treatment in patients with MDD. [ABSTRACT FROM AUTHOR]

LGBTQ+ populations have been reported to have higher rates of depression compared with their heterosexual peers. Such data provided us the impetus to conduct a meta-analysis on the worldwide prevalence of major depressive disorder (MDD) in LGBTQ+ populations and moderating factors that contributed to differences in prevalence estimates between studies. A systematic literature search was performed in major international (PubMed, PsycINFO, Web of Science, EMBASE) and Chinese (Chinese Nation Knowledge Infrastructure (CNKI) and WANFANG) databases from dates of inception to 10 December 2021. 48 articles comprising 4,616,903 individuals were included in the meta-analysis. The overall prevalence of MDD was 32.2 % (95%CI: 30.8–33.6 %, I2 = 99.6 %, τ2 = 0.284). MDD prevalence was higher in the LGBTQ+ samples from the United States than other countries, though the difference was not significant in moderator analyses. Moderator analyses indicated point and lifetime prevalence of MDD were significantly higher than estimates based on the past year (Q = 6.270, p = 0.043). Furthermore, studies that relied on convenience sampling had a higher prevalence of MDD than those based on other sampling methods (Q = 8.159, p = 0.017). In meta-regression analyses, mean age (B = 0.03, z = 9.54, p < 0.001) and study quality assessment score (B = 0.24, z = 67.64, p < 0.001) were positively associated with pooled prevalence of MDD while mediation data of year of study (B = -0.08, z = −72.55, p < 0.001) and sample size (B = -1.46, z = −37.83, p < 0.001) were negatively associated with pooled prevalence of MDD in LGBTQ+ samples. MDD is common among in LGBTQ+ individuals. Considering the negative consequences MDD has on daily life and well-being, appropriate prevention and treatment measures should be provided to vulnerable members of these populations. The findings of this meta-analysis could facilitate identifying at-risk subgroups, developing relevant health policy for LGBTQ+ individuals and allocating health resources from an intersectionality perspective. • This meta-analysis examined the prevalence major depressive disorder (MDD) in LGBTQ+ populations and moderators. • In total, 48 articles comprising 4,618,787 individuals were included, and the overall prevalence of MDD was 32.2%. • The findings of this meta-analysis could facilitate identifying at-risk subgroups, developing relevant health policy for LGBTQ+ individuals. [ABSTRACT FROM AUTHOR]

Abstract Background Major Depressive Disorder (MDD) is one of the most disabling mental health problems worldwide. The Recovery Model emphasizes peer support to empower individuals with MDD, improve self-management, and patients' quality of life. Despite the demonstrated efficacy of peer-led interventions, further research is needed due to methodological limitations and variability in interventions across studies. Therefore, the objective of this trial is to evaluate the effectiveness of an adjuvant peer-led intervention for the reduction of depressive symptoms in individuals diagnosed with MDD attended in primary care mental health units. Methods A controlled, parallel, randomized clinical trial will be conducted. The intervention group (n = 35) will receive 6 weeks of peer-led sessions based on a peer support program drive whilst supervised by nurses, while the control group (n = 35) will use a mobile Health (mHealth) application for emotional wellness based on CBT for 6 weeks. Measurements will be collected at baseline, at 6 weeks, at 6 and 12 months after the intervention to evaluate post-intervention effects. The primary outcome is the reduction of depressive symptoms through the Beck Depression Inventory (BDI-II) after the intervention. Secondary outcomes will involve measures such as adherence to psychiatric treatment, quality of life, adherence to mediterranean diet, alcohol consumption and physical activity. Discussion We hypothesize that this peer-led intervention, in contrast to the mHealth, will show improvement in BDI-II score reduction of 6 points after six weeks, 6 and 12 months. Standardized peer-led programs can benefit patients and professionals in terms of efficacy and feasibility of clinical treatment of depression, healthy habits, self-care and quality of life. In addition, they can provide recovery and relapse reduction, improved psychosocial support, minimization of intensive care use, and support for patient autonomy through self-management. Trial registration The trial protocol is prospectively registered with ClinicalTrials.gov under protocol registration number NCT06398561. Date of registration: May 01, 2024. Recruitment is ongoing.

Abstract Background Tiredness, poor concentration, disturbed sleep and poor appetite can all be caused by depression, which is a common mental disorder and a leading cause of disability worldwide. This study aimed to assess the prevalence of major depressive disorder, suicidal ideation, and risk factors in Sudanese children and adolescents during the Sudanese army conflict. Methods A descriptive cross-sectional community-based study was carried out among Sudanese children between 11 and 17 years old who living in Sudan at the start of the conflict by using a self-administered questionnaire under the guidance of parents, if necessary. The questionnaire was adapted from the Patients Health Questionnaire-9 (PHQ-9) checklist for the assessment of major depression disorder symptoms according to the Diagnostic and Statistical Manual Edition 5th Edition (DSM-5). The questionnaire was translated into Arabic by two expert translators, and its validity and reliability were confirmed. Data analysis was performed using Statistical Package for the Social Sciences version 25 software, and descriptive analysis and any appropriate statistical tests were performed. Results Among the 963 participants, the mean age was 15.18 ± 2.1 years, 65.5% were female, and 67.7% had major depressive disorder. There was a significant relationship between MDD score, age, sex, current residency status, and traumatic event exposure, with P values less than 0.001 for all variables. Conclusion Major depressive disorder was highly prevalent among Sudanese children and adolescents included in the present study. Additionally, suicidal ideation, which requires immediate intervention, was reported to be very high. The findings will help the government to provide proper mental health interventions for affected people.

Objective To investigate whether the effects of venlafaxine on major depression disorder is associated with ankyrin G. Methods Breed Synapsin-Cre1 and Ankyrin3-floxed mice (Ank3 cKO mice). Ank3 cKO mice and wild type mice were randomly divided into model and control groups. All mice in model group and control group were orally administrated with venlafaxine(1 g/L) or the solvent(normal saline, NS) with the volume of 200 μL,respectively. Depression-related behaviors were examined by sucrose preference test (SPT) and Y maze test. The level of ankyrin G and PSD95 in the cortex of four groups were detected by Western blot. The level of ankyrin G and MAP2 in the in hippocampus of four groups were detected by immunohistochemistry method. ResultsCompared with wt-saline group, the cKO mice in saline showed a significantly decreased preference of sucrose (P＜0.001) and low spontaneous alteration(P＜0.05). Compared with cKO control ones, the venlafaxine model cKO mice showed remarkably increased preference of sucrose(P＜0.001) and more spontaneous alteration(P＜0.05). The level of ankyrin G and PSD-95 in the cortex of venlafaxine cKO mice was much higher than that in control mice(P＜0.01)The level of ankyrin G and MAP2 in the hippocampus of venlafaxine cKO mice were much higher than those of control mice(P＜0.05). Conclusions Venlafaxine alleviates the depression symptoms caused by knocking down Ank3. The mechanism of depression treatment by venlafaxine is potentially associated with levitating ankyrin G level in prefrontal cortex and hippocampus.

Studies have been conducted on the relationship between depression and thyroid diseases and function, its causal relationship remains unclear. Using summary statistics of genome-wide association studies of European and East Asian ancestry, we conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid function (European: normal range TSH, T4, T3, fT4, TPOAb levels and TPOAb-positives; East Asian: T4) and thyroid diseases (hypothyroidism, hyperthyroidism, and Hashimoto's thyroiditis), and used Mediation analysis to evaluate potential mediators (alcohol intake, antidepressant) of the association and calculate the mediated proportions. It was observed a significant causal association between MDD on hypothyroidism (P = 8.94 × 10−5), hyperthyroidism (P = 8.68 × 10−3), and hashimoto's thyroiditis (P = 3.97 × 10−5) among European ancestry, which was mediated by Alcohol intake (alcohol intake versus 10 years previously for hypothyroidism (P = 0.026), hashimoto's thyroiditis (P = 0.042), and alcohol intake frequency for hypothyroidism (P = 0.015)) and antidepressant (for hypothyroidism (P = 0.008), hashimoto's thyroiditis (P = 0.010)), but not among East Asian ancestry (P MDD-hypothyroidism = 0.016, but β direction was different; P MDD-hyperthyroidism = 0.438; P MDD-hashimoto ' s thyroiditis = 0.496). There was no evidence for bidirectional causal association between thyroid function mentioned above and MDD among both ancestry (all P > 0.05). We importantly observed a significant causal association between MDD on risk of hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, and Alcohol intake and antidepressant as mediators for prevention of hypothyroidism, hashimoto's thyroiditis attributable to MDD. • We conducted 2-sample bidirectional Mendelian randomization to estimate the association between MDD and thyroid diseases among European and East Asian ancestry and Mediation analysis to evaluate potential mediators (alcohol intake and antidepressant). • It was observed a significant causal association between MDD on hypothyroidism, hyperthyroidism, and hashimoto's thyroiditis among European ancestry, in which MDD on hypothyroidism and hashimoto's thyroiditiswas were mediated by Alcohol intake and antidepressant, but not among East Asian ancestry. • These findings may lead to a shift in personalizing treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Tiredness, poor concentration, disturbed sleep and poor appetite can all be caused by depression, which is a common mental disorder and a leading cause of disability worldwide. This study aimed to assess the prevalence of major depressive disorder, suicidal ideation, and risk factors in Sudanese children and adolescents during the Sudanese army conflict. Methods: A descriptive cross-sectional community-based study was carried out among Sudanese children between 11 and 17 years old who living in Sudan at the start of the conflict by using a self-administered questionnaire under the guidance of parents, if necessary. The questionnaire was adapted from the Patients Health Questionnaire-9 (PHQ-9) checklist for the assessment of major depression disorder symptoms according to the Diagnostic and Statistical Manual Edition 5th Edition (DSM-5). The questionnaire was translated into Arabic by two expert translators, and its validity and reliability were confirmed. Data analysis was performed using Statistical Package for the Social Sciences version 25 software, and descriptive analysis and any appropriate statistical tests were performed. Results: Among the 963 participants, the mean age was 15.18 ± 2.1 years, 65.5% were female, and 67.7% had major depressive disorder. There was a significant relationship between MDD score, age, sex, current residency status, and traumatic event exposure, with P values less than 0.001 for all variables. Conclusion: Major depressive disorder was highly prevalent among Sudanese children and adolescents included in the present study. Additionally, suicidal ideation, which requires immediate intervention, was reported to be very high. The findings will help the government to provide proper mental health interventions for affected people. [ABSTRACT FROM AUTHOR]

Rationale: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate various physiological processes such as inflammation, lipid metabolism, and glucose homeostasis. Recent studies suggest that targeting PPARs could be beneficial in treating neuropsychiatric disorders by modulating neuronal function and signaling pathways in the brain. PPAR-α, PPAR-δ, and PPAR-γ have been found to play important roles in cognitive function, neuroinflammation, and neuroprotection. Dysregulation of PPARs has been associated with neuropsychiatric disorders like bipolar disorder, schizophrenia, major depression disorder, and autism spectrum disorder. The limitations and side effects of current treatments have prompted research to target PPARs as a promising novel therapeutic strategy. Preclinical and clinical studies have shown the potential of PPAR agonists and antagonists to improve symptoms associated with these disorders. Objective: This review aims to provide an overview of the current understanding of PPARs in neuropsychiatric disorders, their potential as therapeutic targets, and the challenges and future directions for developing PPAR-based therapies. Methods: An extensive literature review of various search engines like PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out with the keywords "PPAR, Neuropsychiatric disorders, Oxidative stress, Inflammation, Bipolar Disorder, Schizophrenia, Major depression disorder, Autism spectrum disorder, molecular pathway". Result & Conclusion: Although PPARs present a hopeful direction for innovative therapeutic approaches in neuropsychiatric conditions, additional research is required to address obstacles and convert this potential into clinically viable and individualized treatments. [ABSTRACT FROM AUTHOR]

Purpose: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. Methods: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. Results: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. Conclusions: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) stands as a significant cause of disability globally. Cannabidiolic Acid-Methyl Ester (CBDA-ME) (EPM-301, HU-580), a derivative of Cannabidiol, demonstrates immediate antidepressant-like effects, yet it has undergone only minimal evaluation in psychopharmacology. Our goal was to investigate the behavioral and potential molecular mechanisms associated with the chronic oral administration of this compound in the Wistar Kyoto (WKY) genetic model of treatment-resistant depression. Male WKY rats were subjected to behavioral assessments before and after receiving chronic (14-day) oral doses of CBDA-ME (0.5 mg/kg), 15 mg/kg of imipramine or vehicle. At the end of the study, plasma corticosterone levels and mRNA expression of various genes in the medial Prefrontal Cortex and Hippocampus were measured. Behavioral outcomes from CBDA-ME treatment indicated an antidepressant-like effect similar to imipramine, as oral ingestion reduced immobility and increased swimming duration in the Forced Swim Test. Neither treatment influenced locomotion in the Open Field Test nor preference in the Saccharin Preference Test. The behavioral impact in WKY rats coincided with reduced corticosterone serum levels, upregulated mRNA expression of Cannabinoid receptor 1, Fatty Acid Amide Hydrolase, and Corticotropin-Releasing Hormone Receptor 1, alongside downregulation of the Serotonin Transporter in the hippocampus. Additionally, there was an upregulation of CB1 mRNA expression and downregulation of Brain-Derived Neurotrophic Factor in the mPFC. These findings contribute to our limited understanding of the antidepressant effects of CBDA-ME and shed light on its potential psychopharmacological mechanisms. This discovery opens up possibilities for utilizing cannabinoids in the treatment of major depressive disorder and related conditions. • Cannabinoids have demonstrated potential in the treatment of MDD. • In this study chronic oral ingestion of CBDA- ME was explored in male WKY. • Anti-Depressive-like effect was found in addition to reduced CORT serum levels. • Possible molecular changes were found in the rat's hippocampus and mPFC. • This study exhibits novel discoveriess for utilizing cannabinoids for MDD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Identifying major depression in children and adolescents is more challenging than in adults. Questionnaires are often used for screening or guiding clinical assessment. Several instruments of different lengths are used as equivalent measures in diagnostic decisions. In this paper, we explore to what extent 18 commonly used depression scales for children and adolescents explore depression clinical symptoms as established by standard DSM-5 diagnosis criteria. We analyzed scale content adequacy by examining the overlap between scale contents and consensus clinical symptoms, the diagnostic time frame for active symptom assessment, and readability for the target age group. The 18 scales encompassed 52 distinct symptoms. These scales included just 50% of clinical symptoms required for diagnosis. The content overlap was low; on average, 29% of symptoms coincide across scales. Half of the scales did not use the standard period for active symptom appraisal, and some did not include a period for assessment. The reading levels on six scales were inappropriate for the scale's target population age group. The substantial heterogeneity in defining the depressive syndrome, the low overlap among scales, different periods of a positive diagnosis, and mismatch of reading competence for detecting may lead to heterogeneity in clinical diagnoses when using different scales. Improving the content of self-report in terms of homogeneity of diagnostic criteria would lead to better diagnostic decisions and patient management. [ABSTRACT FROM AUTHOR]

The mental health of faculty in the United States higher education system has been an overlooked area of concern. This study addresses the occupational health of faculty, specifically faculty mental health (i.e., compassion fatigue, generalized anxiety disorder, major depression disorder, somatic symptom disorder), along with psychosocial and occupational factors. Two aspects of compassion fatigue (i.e., secondary traumatic stress and burnout) were used to classify participants into low or elevated secondary traumatic stress and burnout groups. Given the significant rates of compassion fatigue and psychopathology among faculty members, the importance of cultivating resilience at the individual and institutional levels is discussed. [ABSTRACT FROM AUTHOR]

Major depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1. This study utilized machine learning (ML) algorithms to identify critical variables and developed the prediction model for predicting MDD in patients with NT1. The study included 267 NT1 patients from four sleep centers. The diagnosis of comorbid MDD was based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). ML models, including six full models and six compact models, were developed using a training set. The performance of these models was compared in the testing set, and the optimal model was evaluated in the testing set. Various evaluation metrics, such as Area under the receiver operating curve (AUC), precision-recall (PR) curve and calibration curve were employed to assess and compare the performance of the ML models. Model interpretability was demonstrated using SHAP. In the testing set, the logistic regression (LG) model demonstrated superior performance compared to other ML models based on evaluation metrics such as AUC, PR curve, and calibration curve. The top eight features used in the LG model, ranked by feature importance, included social impact scale (SIS) score, narcolepsy severity scale (NSS) score, total sleep time, body mass index (BMI), education years, age of onset, sleep efficiency, sleep latency. The study yielded a straightforward and practical ML model for the early identification of MDD in patients with NT1. A web-based tool for clinical applications was developed, which deserves further verification in diverse clinical settings. • The first study utilizes ML to predict comorbid MDD in patients with NT1. • LG model is the optimal model for prediction of comorbid MDD. • SIS scores, NSS scores, total sleep time and BMI play important role in the LG model. [ABSTRACT FROM AUTHOR]

The diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear. In this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB). We found that the MDD group showed significantly higher power in the high alpha range (10.5–11.5 Hz) and lower power in the low alpha range (7–8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone. Our results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD. • MDD group showed significantly higher power in the high alpha range and lower power in the low alpha range. • High alpha power in the MDD group is negatively correlated with working memory performance in MCCB. • Combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy. [ABSTRACT FROM AUTHOR]

Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of insomnia symptoms in the association between SLEs and SI. This three-wave prospective cohort study sought to investigate the longitudinal association among SLEs, insomnia symptoms, and SI in persons with MDD. The study population included 511 persons with MDD (mean [SD] age, 28.7 [6.7] years; 67.1% were females). Generalized estimated equations (GEEs) were utilized to explore prospective association among exposure of SLEs, insomnia symptoms, and SI. Additionally, a structural equation model (SEM) was employed to estimate the longitudinal mediating effect of insomnia symptoms in the relationship between SLEs and SI. Our study demonstrated that cumulative SLEs were determined to be longitudinally associated with SI in persons with MDD. We further observed that the association between SLEs and SI was significantly mediated by insomnia symptoms. Clinicians assessing persons with MDD, especially those with the history of SLE, could carefully evaluate and promptly treat insomnia symptoms as part of personalized assessment of their depressive illness, thereby achieving early prevention and intervention for suicidal behaviors in persons with MDD. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the effects of venlafaxine on major depression disorder is associated with ankyrin G. Methods Breed Synapsin-Cre1 and Ankyrin3-floxed mice (Ank3 cKO mice). Ank3 cKO mice and wild type mice were randomly divided into model and control groups. All mice in model group and control group were orally administrated with venlafaxine(1 g/L) or the solvent(normal saline, NS) with the volume of 200 μL,respectively. Depression-related behaviors were examined by sucrose preference test (SPT) and Y maze test. The level of ankyrin G and PSD95 in the cortex of four groups were detected by Western blot. The level of ankyrin G and MAP2 in the in hippocampus of four groups were detected by immunohistochemistry method. ResultsCompared with wt-saline group, the cKO mice in saline showed a significantly decreased preference of sucrose (P＜0.001) and low spontaneous alteration(P＜0.05). Compared with cKO control ones, the venlafaxine model cKO mice showed remarkably increased preference of sucrose(P＜0.001) and more spontaneous alteration(P＜0.05). The level of ankyrin G and PSD-95 in the cortex of venlafaxine cKO mice was much higher than that in control mice(P＜0.01)The level of ankyrin G and MAP2 in the hippocampus of venlafaxine cKO mice were much higher than those of control mice(P＜0.05). Conclusions Venlafaxine alleviates the depression symptoms caused by knocking down Ank3. The mechanism of depression treatment by venlafaxine is potentially associated with levitating ankyrin G level in prefrontal cortex and hippocampus. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to investigate the prevalence of cognitive impairment among patients with major depressive disorder (MDD) hospitalized during the acute phase and to analyze the in-depth association between this cognitive impairment and clinical correlation factors.MethodsIn this cross-sectional study, we recruited 126 patients aged between 18 and 65 years who were diagnosed with MDD. All these patients were inpatients from the Department of Psychiatry at the Second People’s Hospital of Hunan Province. We employed a series of assessment tools, including the Pittsburgh Sleep Quality Index (PSQI), the 16-item Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), the Pre-sleep Arousal Scale (PSAS), the Morningness-Eveningness Questionnaire (MEQ), the Hamilton Anxiety Rating Scale (HAMA), and the 17-item Hamilton Depression Rating Scale (HAMD-17). The patients were divided into a cognitive impairment group and a non-cognitive impairment group based on their scores on the Montreal Cognitive Assessment Scale (MoCA). Through Spearman’s correlation analysis, we explored the correlation between the total MoCA score and the score of each factor. Additionally, we utilized binary logistic regression analysis to investigate the relationship between cognitive impairment and clinically relevant factors in MDD patients hospitalized during the acute phase and plotted ROC curves to evaluate their clinical efficacy.ResultsIn this study, we found that the prevalence of cognitive impairment among MDD patients hospitalized during the acute phase was as high as 63.49%. Through statistical analysis, we observed significant differences between the cognitive impairment group and the non-cognitive impairment group in terms of age, place of residence, education level, and HAMD-17 scores. In the Spearman correlation analysis, we noted the following trends: visuospatial and executive abilities were negatively correlated with the HAMD-17 score (P < 0.05); naming ability was positively correlated with the PSAS score but negatively correlated with the MEQ score (P < 0.05); memory was also negatively correlated with the MEQ score (P < 0.05); attention was negatively correlated with the HAMA score; and abstract cognitive ability was negatively correlated with the MEQ score (P < 0.05). Through binary logistic regression analysis, we further revealed the relationship between cognitive impairment and factors such as living in a rural area (OR = 2.7, 95% CI = 1.083-6.731, P < 0.05), increased age (OR = 1.049, 95% CI = 1.013-1.087, P < 0.01), and the HAMD-17 score (OR = 1.10295, 95% CI = 1.031-11.79, P < 0.01). Additionally, ROC curve analysis demonstrated a significant correlation between the HAMD-17 score and the prediction of cognitive function in MDD patients hospitalized during the acute phase (P < 0.001). Specifically, the AUC for the HAMD-17 score was 0.73, with an optimal cut-off value of 19.5, sensitivity of 70.0%, and specificity of 63.0%. Furthermore, the AUC for age was 0.71, with an optimal cut-off value of 33.5, sensitivity of 59.0%, and specificity of 80.0%.ConclusionsThis study indicates that MDD patients hospitalized during the acute phase have a higher prevalence of cognitive impairment. This phenomenon reflects a significant correlation between clinical factors such as age, sleep-related characteristics, and the severity of depression with cognitive impairment. Therefore, regular assessment of cognitive function in MDD patients and early intervention may be crucial for the treatment and prognosis of the disease.

Background: Existing studies have shown that the brain network of major depression disorder (MDD) has abnormal topologies. However, constructing reliable MDD brain networks is still an open problem. New method: This paper proposed a reliable MDD brain network construction method. First, seven connectivity methods are used to calculate the correlation between channels and obtain the functional connectivity matrix. Then, the matrix is binarized using four binarization methods to obtain the EEG brain network. Besides, we proposed an improved binarization method based on the criterion of maximizing differences between groups: the adaptive threshold (AT) method. The AT can automatically set the optimal binarization threshold and overcome the artificial influence of traditional methods. After that, several network metrics are extracted from the brain network to analyze inter-group differences. Finally, we used statistical analysis and Fscore values to compare the performance of different methods and establish the most reliable method for brain network construction. Results: In theta, alpha, and total frequency bands, the clustering coefficient, global efficiency, local efficiency, and degree of the MDD brain network decrease, and the path length of the MDD brain network increases. Comparison with existing methods: The results show that AT outperforms the existing binarization methods. Compared with other methods, the brain network construction method based on phase-locked value (PLV) and AT has better reliability. Conclusions: MDD has brain dysfunction, particularly in the frontal and temporal lobes.

Abstract Depression is a major cause of disability and, if left untreated, can increase the risk of suicide. Evidence on the determinants of depression is incomplete, making it challenging to interpret results across studies. This study aims to identify the social, economic, environmental, political, and technological factors influencing the great recession in Iran. The study was conducted in two parts. The first step involved a literature review to identify the factors, using PubMed, Scopus, and Web of Science for the search. The reference lists of all identified articles were reviewed to find relevant studies, and the extracted information was summarized and reported descriptively. The second steps involved compiling and consulting 14 experts from different fields, using a framework analysis method. Twenty-four articles were used as primary sources of information, and a total of 28 factors were found to exist. After removing duplicates and related factors, 19 of these were subsequently declared as factors, resulting in a total of 36 determinants being identified. Most of these factors belong to the social category. The health policies implemented have a significant impact on disease risk factors and ultimately their occurrence. Political decisions and policy-making processes play a crucial role in all areas, particularly in addressing disease risk factors. Severe depression can disrupt all aspects of the healthcare system, underscoring the importance of access to care. Policies concerning physical education, transportation, nutrition, employment, green spaces, recreational facilities, and tobacco are vital in this context. The influence of health policies on disease risk factors and disease occurrence is profound. Severe depression can have far-reaching effects on the healthcare system, emphasizing the critical need for access to care. The formulation of policies to combat depression must be thoroughly evaluated in terms of economic, political, social, technological, and environmental factors. The findings suggest that addressing social inequalities and emphasizing the role of political action, as highlighted by the social determinants of health, should be top priorities in addressing depression. Efforts to prevent depression should incorporate ecological approaches that consider the impact of the socioeconomic environment on depressive symptoms.

Depression is a major cause of disability and, if left untreated, can increase the risk of suicide. Evidence on the determinants of depression is incomplete, making it challenging to interpret results across studies. This study aims to identify the social, economic, environmental, political, and technological factors influencing the great recession in Iran. The study was conducted in two parts. The first step involved a literature review to identify the factors, using PubMed, Scopus, and Web of Science for the search. The reference lists of all identified articles were reviewed to find relevant studies, and the extracted information was summarized and reported descriptively. The second steps involved compiling and consulting 14 experts from different fields, using a framework analysis method. Twenty-four articles were used as primary sources of information, and a total of 28 factors were found to exist. After removing duplicates and related factors, 19 of these were subsequently declared as factors, resulting in a total of 36 determinants being identified. Most of these factors belong to the social category. The health policies implemented have a significant impact on disease risk factors and ultimately their occurrence. Political decisions and policy-making processes play a crucial role in all areas, particularly in addressing disease risk factors. Severe depression can disrupt all aspects of the healthcare system, underscoring the importance of access to care. Policies concerning physical education, transportation, nutrition, employment, green spaces, recreational facilities, and tobacco are vital in this context. The influence of health policies on disease risk factors and disease occurrence is profound. Severe depression can have far-reaching effects on the healthcare system, emphasizing the critical need for access to care. The formulation of policies to combat depression must be thoroughly evaluated in terms of economic, political, social, technological, and environmental factors. The findings suggest that addressing social inequalities and emphasizing the role of political action, as highlighted by the social determinants of health, should be top priorities in addressing depression. Efforts to prevent depression should incorporate ecological approaches that consider the impact of the socioeconomic environment on depressive symptoms. [ABSTRACT FROM AUTHOR]

As research progresses, there has been growing interest in the association between Alopecia areata (AA) and anxiety, as well as depression. However, there have been limited reports on the genetic variation level of AA in relation to mental disorders. We performed large-scale Two sample Mendelian randomization (MR) analyses to examine whether there is a association between AA with anxiety and depression. The data utilized for AA analysis were sourced from the FinnGen release 9 databases, including 682 cases and 361,822 controls. Summary statistics for major depression disorder (MDD) were obtained from a genome-wide meta-analysis dataset, incorporating 170,756 cases and 329,443 controls. The anxiety disorder data was conducted by the Anxiety Neuro Genetics Study Consortium, including 5580 cases and 11,730 controls. We employed four distinct approaches, including MR-Egger, weighted median, random-effect inverse variance weighted (IVW), and weighted mode, to conduct the MR analysis. Genetic liability to AA was associated with an increased risk of Major depression disorder (MDD) and anxiety demonstrated an odds ratio (OR) of 1.01 (βivw = 0.011, PIVW = 0.023) and OR of 1.16 (βivw = 0.150, PIVW = 0.002). Upon conducting the Bonferroni correction, the P -values were 0.046 and 0.004, respectively. For reverse analysis, we observed no significant association between anxiety and MDD with the risk of AA. Our research unveil a unidirectional causal association whereby AA exerts a risk effect against MDD and anxiety, which serves as a valuable complement to prior meta-analyses, enriching the existing body of knowledge on the subject matter. • Unidirectional causal link found between AA and MDD/anxiety. • GRM8 may be a significant gene associated with AA, MDD, and anxiety. • Comorbidity due to combined environmental and genetic factors. [ABSTRACT FROM AUTHOR]

Major Depression Disorder (MDD) is a common yet destructive mental disorder that affects millions of people worldwide. Making early and accurate diagnosis of it is very meaningful. Recently, EEG, a non-invasive technique of recording spontaneous electrical activity of brains, has been widely used for MDD diagnosis. However, there are still some challenges in data quality and data size of EEG: (1) A large amount of noise is inevitable during EEG collection, making it difficult to extract discriminative features from raw EEG; (2) It is difficult to recruit a large number of subjects to collect sufficient and diverse data for model training. Both of the challenges cause the overfitting problem, especially for deep learning methods. In this paper, we propose DiffMDD, a diffusion-based deep learning framework for MDD diagnosis using EEG. Specifically, we extract more noise-irrelevant features to improve the model’s robustness by designing the Forward Diffusion Noisy Training Module. Then we increase the size and diversity of data to help the model learn more generalized features by designing the Reverse Diffusion Data Augmentation Module. Finally, we re-train the classifier on the augmented dataset for MDD diagnosis. We conducted comprehensive experiments to test the overall performance and each module’s effectiveness. The framework was validated on two public MDD diagnosis datasets, achieving the state-of-the-art performance.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective in regulating mood and high-level cognition in patients with major depressive disorder (MDD). This study aimed to investigate the efficacy of taVNS treatment in patients with MDD and an altered brain topological organization of functional networks. Methods: Nineteen patients with MDD were enrolled in this study. Patients with MDD underwent 4 weeks of taVNS treatments; resting-state functional magnetic resonance imaging (rs-fMRI) data of the patients were collected before and after taVNS treatment. The graph theory method and network-based statistics (NBS) analysis were used to detect abnormal topological organizations of functional networks in patients with MDD before and after taVNS treatment. A correlation analysis was performed to characterize the relationship between altered network properties and neuropsychological scores. Results: After 4 weeks of taVNS treatment, patients with MDD had increased global efficiency and decreased characteristic path length (Lp). Additionally, patients with MDD exhibited increased nodal efficiency (NE) and degree centrality (DC) in the left angular gyrus. NBS results showed that patients with MDD exhibited reduced connectivity between default mode network (DMN)–frontoparietal network (FPN), DMN–cingulo-opercular network (CON), and FPN–CON. Furthermore, changes in Lp and DC were correlated with changes in Hamilton depression scores. Conclusions: These findings demonstrated that taVNS may be an effective method for reducing the severity of depressive symptoms in patients with MDD, mainly through modulating the brain’s topological organization. Our study may offer insights into the underlying neural mechanism of taVNS treatment in patients with MDD.

Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision‐making, and risk‐taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision‐making, and risk‐taking behavior in BD and MDD patients from bipolar multiplex families. Methods: Eighty‐two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision‐making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains. Results: Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision‐making was associated with both mood disorders (BD and MDD). In risk‐taking behavior, no significant impairment was found in any group. Limitations: As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power. Conclusions: Our findings show that alterations of cognitive domains—while present in both disorders—are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders. [ABSTRACT FROM AUTHOR]

ProBDNF is the precursor protein of brain‐derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL‐1β and IL‐10 were also positively correlated with the major depression scores, while the levels of TNF‐α and IL‐6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL‐1β. Q‐PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD‐Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD‐Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD. [ABSTRACT FROM AUTHOR]

Anxious depression (AD) has been extensively studied. However, fewer studies have examined sex differences in the prevalence of suicide attempts among AD patients. This study aimed to explore sex differences in suicide attempts and risk factors in patients with AD. 1380 first episode drug-naïve patients with AD were recruited. Sociodemographic and clinical characteristics were measured using a self-administered demographic questionnaire. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Inventory (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess patients' clinical symptoms. We also measured the patient's blood glucose, lipids, and thyroid axis hormone levels. There were no sex differences in the prevalence of suicide attempts in patients with FEDN anxious depression. In addition, binary logistic regression analysis showed that HAMA score, TSH levels, and TPOAb levels significantly predicted suicide attempts in both male and female patients with AD, while HAMD score significantly predicted suicide attempts in female patients with AD only. The severity of anxiety and higher levels of TSH and TPOAb were associated with an increased risk for suicide attempts in both male and female patients with AD, whereas the severity of depression was only associated with suicide attempts in females. • To our knowledge, this is the first large-scale clinical study to examine sex differences in suicide attempts among FEDN patients with AD in the Chinese Han population. The present results suggest that: • (1) the onset age of female patients with AD was older than that of male patients; • (2) there was no sex difference in the prevalence of suicide attempts in AD patients; • (3) HAMA score, TSH levels, and TPOAb levels significantly predicted suicide attempts in both male and female patients with AD. [ABSTRACT FROM AUTHOR]

Prior studies have discussed rapid eye movement (REM) sleep disturbance as a potential endophenotype of major depressive disorder (MDD). However, the neural substrates underlying the percentage of REM sleep duration (REM%) and its association with disease progression in MDD remain unclear. One hundred and fourteen MDD patients and 74 healthy controls (HCs) underwent resting-state functional and perfusion magnetic resonance imaging (MRI) scans as well as overnight polysomnography examination to assess brain function and REM%, with 48 patients completing follow-up visits. Correlation and mediation analyses were conducted to investigate the associations among baseline REM%, multimodal brain imaging measures, and the improvement of depressive symptoms at follow-up in MDD. We found voxel-wise correlations between baseline REM% and multimodal brain imaging metrics in many brain regions involved in sensorimotor, visual processing, emotion, and cognition in patients with MDD. Moreover, the baseline REM% was correlated with the improvement of depressive symptoms from acute to remitted status in patients through regulating brain activity in the left inferior temporal gyrus and cerebral blood flow in the bilateral paracentral lobule. Our findings help to identify the neural underpinnings of REM% in depression and highlight REM% as a potential prognostic biomarker to predict disease progression. These may inform future novel interventions of MDD from the perspective of regulating REM sleep. • MDD patients exhibited abnormal rapid eye movement sleep duration (REM%). • REM% is related to multimodal brain functional imaging measures in MDD. • Baseline REM% could predict symptom improvement via changing brain function in MDD. [ABSTRACT FROM AUTHOR]

Background: Mental, emotional, and behavioral disorders are chronic pediatric conditions, and their prevalence has been on the rise over recent decades. Affected children have long-term health sequelae and a decline in health-related quality of life. Due to the lack of a validated database for pharmacoepidemiological research on selected mental, emotional, and behavioral disorders, there is uncertainty in their reported prevalence in the literature. Objectives: We aimed to evaluate the accuracy of coding related to pediatric mental, emotional, and behavioral disorders in a large integrated health care system's electronic health records (EHRs) and compare the coding quality before and after the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding as well as before and after the COVID-19 pandemic. Methods: Medical records of 1200 member children aged 2-17 years with at least 1 clinical visit before the COVID-19 pandemic (January 1, 2012, to December 31, 2014, the ICD-9-CM coding period; and January 1, 2017, to December 31, 2019, the ICD-10-CM coding period) and after the COVID-19 pandemic (January 1, 2021, to December 31, 2022) were selected with stratified random sampling from EHRs for chart review. Two trained research associates reviewed the EHRs for all potential cases of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), major depression disorder (MDD), anxiety disorder (AD), and disruptive behavior disorders (DBD) in children during the study period. Children were considered cases only if there was a mention of any one of the conditions (yes for diagnosis) in the electronic chart during the corresponding time period. The validity of diagnosis codes was evaluated by directly comparing them with the gold standard of chart abstraction using sensitivity, specificity, positive predictive value, negative predictive value, the summary statistics of the F-score, and Youden J statistic. κ statistic for interrater reliability among the 2 abstractors was calculated. Results: The overall agreement between the identification of mental, behavioral, and emotional conditions using diagnosis codes compared to medical record abstraction was strong and similar across the ICD-9-CM and ICD-10-CM coding periods as well as during the prepandemic and pandemic time periods. The performance of AD coding, while strong, was relatively lower compared to the other conditions. The weighted sensitivity, specificity, positive predictive value, and negative predictive value for each of the 5 conditions were as follows: 100%, 100%, 99.2%, and 100%, respectively, for ASD; 100%, 99.9%, 99.2%, and 100%, respectively, for ADHD; 100%, 100%, 100%, and 100%, respectively for DBD; 87.7%, 100%, 100%, and 99.2%, respectively, for AD; and 100%, 100%, 99.2%, and 100%, respectively, for MDD. The F-score and Youden J statistic ranged between 87.7% and 100%. The overall agreement between abstractors was almost perfect (κ=95%). Conclusions: Diagnostic codes are quite reliable for identifying selected childhood mental, behavioral, and emotional conditions. The findings remained similar during the pandemic and after the implementation of the ICD-10-CM coding in the EHR system. INSET: cc. [ABSTRACT FROM AUTHOR]

Background: Since depression, sex hormones, and fatty acid status are interrelated, it is important to understand their relationships. In this study, we aimed to investigate sex differences in erythrocyte membrane fatty acid composition among first-diagnosed, drug-naïve patients with major depressive disorders. Methods: The study included 139 individuals with first-diagnosed, drug-naïve depression (male/female = 48/91) and 55 healthy controls (male/female = 24/31). The levels of erythrocyte membrane fatty acids were analyzed to compare the difference between males and females in both patients with depression and healthy controls, as well as to study their correlation with depressive symptoms. Results: In first-diagnosed, drug-naïve patients with major depressive disorders, sex disparities were observed in the levels of erythrocyte saturated fatty acids (SFAs) and n-6 PUFAs (such as C18:0, C20:4n6 and C22:4n6), where higher levels evident in females compared to in males. We found a noteworthy correlation between fatty acid levels and depressive symptoms, in which there is a significant association between female patients and depression but a weaker association between male patients and depression. Conclusion: Our findings demonstrate higher levels of n-6 PUFAs and SFAs in female patients with depression. The relationship between fatty acid composition and depressive symptoms was more prominent in females than males. These findings highlight the significance of considering sex as a crucial and interconnected factor in future investigations and potential adjunctive treatment for mood disorders by targeting fatty acid metabolism. [ABSTRACT FROM AUTHOR]

Shuangyu Qi,1,2,&ast; Yang Xu,1,2,&ast; Kuan Zeng,1,2 Yi Li,1,2 Jun Ma1– 3 1Affiliated Wuhan Mental Health Center, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Wuhan Hospital for Psychotherapy, Wuhan, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Li; Jun Ma, Affiliated Wuhan Mental Health Center, Tongji Medical College of Huazhong University of Science and Technology, No. 89, Gongnongbing Road, Wuhan, Hubei Province, People’s Republic of China, Tel +86 027 82281733, Fax +86-027-82281733, Email psylee@163.com; majun0313@msn.cnPurpose: Major depressive disorder (MDD) is a mood disorder characterized by persistent spontaneous depression and has a high rate of disability and mortality. There is a complex relationship between MDD and disorders of glucose metabolism, and our study aimed to investigate the prevalence and risk factors for hyperglycemia in patients with MDD who were hospitalized for the first times.Patients and Methods: A total of 981 first-time inpatients with MDD were recruited, socio-demographic information, anthropometric data, and biochemical parameters were collected for each participant. The 17-item Hamilton Assessment Scale for Depression (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive Syndrome Scale (PSS), and Clinical General Impressions Inventory-Severity of Illness (CGI-SI) scores were used to assess patients’ clinical symptoms.Results: The prevalence of hyperglycemia was 9.28% among patients with MDD who were hospitalized for the first time. Compared to the non-hyperglycemic subgroup, patients in the hyperglycemic subgroup were found to have more extensive and significant demographic and clinical characteristics, higher levels of metabolism-related parameters, and more severe psychological and psycho-pathological symptoms. Age, thyroid stimulating hormone (TSH), triglycerides (TG) were risk factors for hyperglycemia in MDD patients, while course of disease was a protective factor.Conclusion: The study findings suggest that the prevalence of hyperglycemia is not high in patients with MDD who are hospitalized for the first time. The risk variables for predicting hyperglycemia include age, TSH and TG. The above three factors and course of disease have good combined diagnostic ability for hyperglycemia.Keywords: major depression disorder, hyperglycemia, first hospitalization, incidence

Abstract Background Observational studies have revealed a link between major depressive disorder (MDD) and a higher chance of developing atrial fibrillation (AF). It is still uncertain whether or not this correlation indicates a causal relationship. This research set out to evaluate the causal impact of MDD on AF. Methods To evaluate the causal relationship between MDD and AF, we employed a two-sample Mendelian randomization (MR) method. A new genome-wide association study (GWAS) with 500,199 participants was used to obtain an overview of the association of genetic variations with MDD. An additional GWAS incorporating 1,030,836 people provided data on the relationship between gene variants and AF. The inverse-variance weighted technique was utilized to assess the effect sizes. Sensitivity analysis included the use of other statistical approaches such as weighted median, Outlier, MR Pleiotropy Residual Sum, weighted mode, simple mode, and MR - Egger. Results By employing 47 single nucleotide polymorphisms (SNPs) as markers, MR analyses in random-effect inverse-variance weighted models found that genetically projected MDD was linked to an elevated incidence of AF (odds ratio [OR] = 1.098, 95% CI 1.000–1.206; P = 0.049). No gene pleiotropy was discovered as indicated by MR-Egger (intercept= -0.011, P = 0.169). Sensitivity analysis employing other MR techniques yielded reliable results. Conclusion This MR study established a causal relationship between genetically predicted MDD and an elevated risk of AF.

Abstract Objectives Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision‐making, and risk‐taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision‐making, and risk‐taking behavior in BD and MDD patients from bipolar multiplex families. Methods Eighty‐two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision‐making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains. Results Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision‐making was associated with both mood disorders (BD and MDD). In risk‐taking behavior, no significant impairment was found in any group. Limitations As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power. Conclusions Our findings show that alterations of cognitive domains—while present in both disorders—are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders.

Context: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to exhibit anti-depressive effects in clinical trials. However, the direct mechanism underlying its effect on neuroinflammation remains unclear. Neuroinflammatory reaction from astrocytes leads to depression, and our previous study found that gap junction disorder between astrocytes aggravated neuroinflammatory reaction in depressed mice. Objective: To investigate the potential mechanism of celecoxib's effects on astrocytic gap junctions during the central nervous inflammation-induced depression. Materials & methods: Stereotaxic injection of lipopolysaccharide (LPS) into the prefrontal cortex (PFC) to establish a model of major depressive disorder (MDD). Celecoxib was administrated into PFC 15 min after LPS injection. The depressive performance was tested by tail suspension test and forced swimming test, and the levels of proinflammation cytokines were determined at mRNA and protein levels. Resting-state functional connection (rsFC) was employed to assess changes in the default mode network (DMN). Additionally, astrocytic gap junctions were also determined by lucifer yellow (LY) diffusion and transmission electron microscope (TEM), and the expression of connexin 43 (Cx43) was measured by western blotting, quantitative polymerase chain reaction, and immunofluorescence. Results: LPS injection induced significant depressive performance, which was ameliorated by celecoxib treatment. Celecoxib also improved rsFC in the DMN. Furthermore, celecoxib improved astrocytic gap junctions as evidenced by increased LY diffusion, shortened gap junction width, and normalized levels of phosphorylated Cx43. Celecoxib also blocked the phosphorylation of p65, and inhibition of p65 abolished the improvement of Cx43. Discussion & conclusion: Anti-depressive effects of celecoxib are mediated, at least in part, by the inhibition of nuclear factor- kappa B (NF-κB) and the subsequent improvement of astrocytic gap junction function

Background: Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined. Methods: 85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables. Results: A significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: −0.006, 95 % CI: −0.0108 – −0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables. Conclusions: Based on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia.

Patients with major depressive disorders (MDD) who exercise report better quality of sleep, but there is a need for more conclusive evidence. This systematic review sought to gather data only from randomized controlled trials (RCTs) that looked at how physical activity affects the quality of sleep in patients with MDD. Three e-databases (Web of Sciences, Scopus, and PubMed) were searched for relevant RCTs in January 2021. Ten RCTs (768 participants) with a total of 24 articles were deemed eligible, including RCTs with clinically diagnosed MDD. Across the studies, physical activity was found to improve sleep quality among people with MDD. However, the limitations of this systematic review include the few available trials, the small number of samples with clinically diagnosed MDD patients, and the wide range of exercise modalities. The physical activity enhanced sleep quality in people with MDD, especially in RCTs with 150 min per week moderate intensity interventions. Although more RCTs are required to examine the effects of physical activity among people with MDD, these findings are clinically useful. [ABSTRACT FROM AUTHOR]

Major depression disorder (MDD) is a neuropsychiatric disorder associated with a high suicide rate and a higher disability rate than any other disease. Evidence suggests that the pathological mechanism of MDD is related to astrocyte dysfunction. Depression is mainly associated with the expression of connexin 43 (Cx43) and the function of Cx43-mediated gap junctions and hemichannels in astrocytes. Moreover, neuroinflammation has been a hotspot in research on the pathology of depression, and Cx43-mediated functions are thought to be involved in neuroinflammation-related depression. However, the specific mechanism of Cx43-mediated functions in neuroinflammation-related depression pathology remains unclear. Therefore, this review summarizes and discusses Cx43 expression, the role of gap junction intercellular communication, and its relationship with neuroinflammation in depression. This review also focuses on the effects of antidepressant drugs (e.g., monoamine antidepressants, psychotropic drugs, and N-methyl-d-aspartate receptor antagonists) on Cx43-mediated function and provides evidence for Cx43 as a novel target for the treatment of MDD. The pathogenesis of MDD is related to astrocyte dysfunction, with reduced Cx43 expression, GJ dysfunction, decreased GJIC and reduced BDNF expression in the depressed brain. The effect of Cx43 on neuroinflammation-related depression involving inflammatory cytokines, glutamate excitotoxicity, and HPA axis dysregulation. Antidepressant drugs targeting Cx43 can effectively relieve depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found qualitative structural and functional brain changes in major depressive disorder (MDD) patients. However, most studies ignored the complementarity of multisequence MRI neuroimaging features and cannot determine accurate biomarkers. Purpose: To evaluate machine‐learning models combined with multisequence MRI neuroimaging features to diagnose patients with MDD. Study Type: Prospective. Subjects: A training cohort including 111 patients and 90 healthy controls (HCs) and a test cohort including 28 patients and 22 HCs. Field Strength/Sequence: A 3.0 T/T1‐weighted imaging, resting‐state functional MRI with echo‐planar sequence, and single‐shot echo‐planar diffusion tensor imaging. Assessment: Recruitment and integration were used to reflect the dynamic changes of functional networks, while gray matter volume and fractional anisotropy were used to reflect the changes in the morphological and anatomical network. We then fused features with significant differences in functional, morphological, and anatomical networks to evaluate a random forest (RF) classifier to diagnose patients with MDD. Furthermore, a support vector machine (SVM) classifier was used to verify the stability of neuroimaging features. Linear regression analyses were conducted to investigate the relationships among multisequence neuroimaging features and the suicide risk of patients. Statistical Tests: The comparison of functional network attributes between patients and controls by two‐sample t‐test. Network‐based statistical analysis was used to identify structural and anatomical connectivity changes between MDD and HCs. The performance of the model was evaluated by receiver operating characteristic (ROC) curves. Results: The performance of the RF model integrating multisequence neuroimaging features in the diagnosis of depression was significantly improved, with an AUC of 93.6%. In addition, we found that multisequence neuroimaging features could accurately predict suicide risk in patients with MDD (r = 0.691). Data Conclusion: The RF model fusing functional, morphological, and anatomical network features performed well in diagnosing patients with MDD and provided important insights into the pathological mechanisms of MDD. Evidence Level: 1. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

Major Depression Disorder (MDD) and pain appear to be reciprocal risk factors and sharing common neuroanatomical pathways and biological substrates. However, the role of MDD on pain processing remains still unclear. Therefore, this review aims to focus on the effect of depression on pain anticipation, and perception, before and after treatment, through functional magnetic resonance imaging (fMRI). A bibliographic search was conducted on PubMed, Scopus and Web of Science, looking for fMRI studies exploring pain processing in MDD patients. Amongst the 602 studies retrieved, 12 met the inclusion criteria. In terms of pain perception, studies evidenced that MDD patients generally presented increased activation in brain regions within the prefrontal cortex, insula and in the limbic system (such as amygdala, hippocampus) and occipital cortex. The studies investigating the effect of antidepressant treatment evidenced a reduced activation in areas such as insula, anterior cingulate, and prefrontal cortices. In terms of pain anticipation, contrasting results were evidenced in MDD patients, which presented both increased and decreased activity in the prefrontal cortex, the insula and the temporal lobe, alongside with increased activity in the anterior cingulate cortex, the frontal gyrus and occipital lobes. The small number of included studies, the heterogeneous approaches of the studies might limit the conclusions of this review. Acute pain processing in MDD patients seems to involve numerous and different brain areas. However, more specific fMRI studies with a more homogeneous population and rigorous approach should be conducted to better highlight the effect of depression on pain processing. • This review summarizes the results from fMRI studies on pain processing in depression. • In terms of pain perception, MDD patients present increased activation in brain regions within the prefrontal cortex, insula, limbic system, and occipital cortex. • Antidepressant treatment reduced activation in insula, anterior cingulate, and prefrontal cortices. • In terms of pain anticipation, MDD patients present both increased and decreased activity in the prefrontal cortex, the insula and the temporal lobe. • fMRI studies with a more homogeneous population and rigorous approaches should be conducted to better investigate the effect of depression on pain processing. [ABSTRACT FROM AUTHOR]

• BD+SUD showed more cognitive impairment than each disorder separately. • Improvement in depression could enhance cognitive functioning in DD patients. • Attention and executive functions were the most impaired functions in both DD groups. • Memory seems to be more clearly impaired in MDD+SUD group. • Cognitive impairment may influence clinical variables like abstinence and relapses. Major depression disorder (MDD) and bipolar disorder (BD) are usual comorbidities in patients with substance use disorders (SUD), a condition known as dual disorder (DD). MDD, BD and SUD are associated with cognitive impairment, potentially leading to a greater functional impairment in the context of DD. Objectives: To review the existing data on the cognitive impairment in DD patients with comorbid MDD or BD, considering the influence of the depressive symptomatology. Methods: Following the PRISMA protocol 19 studies were selected from the last 17 years, 13 of which focused on BD, five on MDD and one included both diagnoses. Results: Studies based in BD+SUD showed that the most affected cognitive domains were attention and executive functions, but not all of them found a greater impairment due to the comorbidity. While fewer studies were found for depression, MDD+SUD works point to a similar impairment cognitive pattern. Furthermore, depression improvement could be associated to better cognitive performance. Limitations: More standardized research is needed regarding the influence of depression on cognitive performance of DD patients, especially on those with comorbid MDD. Factors such as main substance, abstinence, or MDD/BD-related variables should be considered. Unstudied factors, like gender or circadian rhythms, are proposed to improve knowledge in this area. Conclusions: Current studies suggest that DD could potentiate cognitive impairment in BD, MDD and SUD. However, additional research is needed to improve the understanding of comorbidity to apply more individualized therapies in the treatment of these patients, considering the interference of their neurocognitive functioning. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is the most common and widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD. The relation between the inhibition of serotonin reuptake in the central nervous system and remission from MDD remains controversial, as reuptake inhibition occurs rapidly, but remission from MDD takes weeks to months. Myelination-related deficits and white matter abnormalities were shown to be involved in psychiatric disorders such as MDD. This may explain the delay in remission following SSRI administration. The raphe nuclei (RN), located in the brain stem, consist of clusters of serotonergic (5-HT) neurons that project to almost all regions of the brain. Thus, the RN are an intriguing area for research of the potential effect of SSRI on myelination, and their involvement in MDD. MicroRNAs (miRNAs) regulate many biological features that might be altered by antidepressants. Two cohorts of chronic unpredictable stress (CUS) mouse model for depression underwent behavioral tests for evaluating stress, anxiety, and depression levels. Following application of the CUS protocol and treatment with the SSRI, citalopram, 48 mice of the second cohort were tested via magnetic resonance imaging and diffusion tensor imaging for differences in brain white matter tracts. RN and superior colliculus were excised from both cohorts and measured for changes in miRNAs, mRNA, and protein levels of candidate genes. Using MRI-DTI scans we found lower fractional anisotropy and axial diffusivity in brains of stressed mice. Moreover, both miR-30b-5p and miR-101a-3p were found to be downregulated in the RN following CUS, and upregulated following CUS and citalopram treatment. The direct binding of these miRNAs to Qki, and the subsequent effects on mRNA and protein levels of myelin basic protein (Mbp), indicated involvement of these miRNAs in myelination ultrastructure processes in the RN, in response to CUS followed by SSRI treatment. We suggest that SSRIs are implicated in repairing myelin deficits resulting from chronic stress that leads to depression. [ABSTRACT FROM AUTHOR]

Predicting clinical response to repetitive transcranial magnetic stimulation (rTMS) in medication-resistant depression (MRD) has gained great importance in recent years. Mainly, the right subgenual anterior cingulate cortex (sgACC) functional connectivity has been put forward as biomarker in relation to rTMS clinical outcome. Even though the left and right sgACC may have different neurobiological functions, little is known about the possible lateralized predictive role of the sgACC in rTMS clinical outcome. In 43 right-handed antidepressant-free MRD patients, we applied a searchlight-based interregional covariance connectivity approach using the baseline 18FDG-PET scan—collected from two previous high-frequency (HF)-rTMS treatment studies delivering stimulation to the left dorsolateral prefrontal cortex (DLPFC)—and investigated whether unilateral or bilateral sgACC glucose metabolism at baseline would result in different predictive metabolic connectivity patterns. Regardless of sgACC lateralization, the weaker the sgACC seed-based baseline metabolic functional connections with the (left anterior) cerebellar areas, the significantly better the clinical outcome. However, the seed diameter seems to be crucial. Similar significant findings on sgACC metabolic connectivity with the left anterior cerebellum, also unrelated to sgACC lateralization, in relation to clinical outcome were observed when using the HCPex atlas. Although we could not substantiate that specifically right sgACC metabolic connectivity would predict HF-rTMS clinical outcome, our findings suggest considering the entire sgACC in functional connectivity predictions. Given that the interregional covariance connectivity results were significant only when using the Beck Depression Inventory (BDI-II) and not with the Hamilton Depression Rating Scale (HDRS), our sgACC metabolic connectivity observations also suggest the possible involvement of the (left) anterior cerebellum involved in higher-order cognitive processing as part of this predictive value. [ABSTRACT FROM AUTHOR]

Stressful life events (SLEs) and suicidal ideation (SI) are prevalent in persons with major depression disorder (MDD). Less is known about the underlying role of insomnia symptoms in the association between SLEs and SI. This three-wave prospective cohort study sought to investigate the longitudinal association among SLEs, insomnia symptoms, and SI in persons with MDD. The study population included 511 persons with MDD (mean [SD] age, 28.7 [6.7] years; 67.1% were females). Generalized estimated equations (GEEs) were utilized to explore prospective association among exposure of SLEs, insomnia symptoms, and SI. Additionally, a structural equation model (SEM) was employed to estimate the longitudinal mediating effect of insomnia symptoms in the relationship between SLEs and SI. Our study demonstrated that cumulative SLEs were determined to be longitudinally associated with SI in persons with MDD. We further observed that the association between SLEs and SI was significantly mediated by insomnia symptoms. Clinicians assessing persons with MDD, especially those with the history of SLE, could carefully evaluate and promptly treat insomnia symptoms as part of personalized assessment of their depressive illness, thereby achieving early prevention and intervention for suicidal behaviors in persons with MDD.

BackgroundMajor depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagnosing MDD based on ferroptosis-related genes (FRGs) and further explore the biological functions of these genes in MDD.MethodsThe datasets were downloaded from the Gene Expression Omnibus (GEO) database and FRGs were obtained from the FerrDb database and other literatures. Least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were performed to develop a gene signature. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic power of the signature. Gene ontology (GO) enrichment analysis was used to explore the biological roles of these diagnostic genes, and single sample gene set enrichment analysis (ssGSEA) algorithm was used to evaluate immune infiltration in MDD. Animal model of depression was constructed to validate the expression of the key genes.ResultsEleven differentially expressed FRGs were identified in MDD patients compared with healthy controls. A signature of three FRGs (ALOX15B, RPLP0, and HP) was constructed for diagnosis of MDD. Afterwards, ROC analysis confirmed the signature’s discriminative capacity (AUC = 0.783, 95% CI = 0.719–0.848). GO enrichment analysis revealed that the differentially expressed genes (DEGs) related to these three FRGs were mainly involved in immune response. Furthermore, spearman correlation analysis demonstrated that these three FRGs were associated with infiltrating immune cells. ALOX15B and HP were significantly upregulated and RPLP0 was significantly downregulated in peripheral blood of the lipopolysaccharide (LPS)-induced depressive model.ConclusionOur results suggest that the novel FRG signature had a good diagnostic performance for MDD, and these three FRGs correlated with immune infiltration in MDD.

Mindfulness training among patients with major depressive disorder (MDD) reduces symptoms, prevents relapse, improves prognosis, and is more efficient for those with a high level of trait mindfulness. Upon hospital admission, 126 MDD patients completed the Beck Depression Inventory (BDI), World Health Organization Quality of Life Brief, Five-Factor Mindfulness Questionnaire (FFMQ), and the Rumination Response Scale (RRS). The 65 patients that scored less than the median of all subjects on the FFMQ were placed into the low mindfulness level (LML) group. The other 61 patients were placed in the high mindfulness level (HML) group. All facet scores were statistically different between the mental health assessment scores of the HML and LML groups except for RRS brooding and FFMQ nonjudgement. Trait mindfulness level exhibited a negative and bidirectional association with MDD severity primarily through the facets of description and aware actions. Trait mindfulness was also related positively with age primarily through the facets of nonreactivity and nonjudgement. Being married is positively associated with trait mindfulness levels primarily through the facet of observation and by an associated increase in perceived quality of life. Mindfulness training prior to MDD diagnosis also associates positively with trait mindfulness level. Hospitalized MDD patients should have their trait mindfulness levels characterized to predict treatment efficiency, help establish a prognosis, and identify mindfulness-related therapeutic targets. [ABSTRACT FROM AUTHOR]

Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear. To unveil the causal associations between sexual factors and major depression disorder (MDD). The bidirectional, two-sample Mendelian randomization (MR) study was conducted, which used genetic variants associated with two sexual factors (age first had sexual intercourse, n = 406,457; lifetime number of sexual partners, n = 378,882) and MDD (n = 500,199) from the largest genome-wide association studies (GWASs) conducted by the UK biobank and the Psychiatric Genomics Consortium. The two-step MR analysis was applied to assess mediation. The Genetic predictors for five risky behaviors were also obtained from the most up-to-date GWAS conducted by the UK Biobank (ever self-harmed: 117,733; ever attempted suicide: 4933; psychoactive substance abuse, alcohol use, and tobacco use: 463,010). MR analysis indicated a risky causal effect of age first had sexual intercourse (OR = 0.720, 95 % CI: 0.661–0.784, P = 2.45 × 10−14) and lifetime number of sexual partners (OR = 1.656, 95 % CI: 1.356–2.022, P = 7.46 × 10−7) on MDD. Mediation analysis showed the effects were mediated by tobacco use, with a proportion of 34.20 % on age first had sexual intercourse and 22.94 % on lifetime number of sexual partners separately. The overlap of participants in different traits and unclear gender. Robust genetic evidence indicated that premature sexual intercourse and more sexual partners were risks for MDD. Risky behaviors, especially the tobacco use, mediated this effect. • The causality between sexual factors and depression was still not clear. • Data were from the largest the largest genome-wide association studies. • MR analysis indicated a risky causal effect of sexual factors on depression. • Mediation analysis showed the causal effects were mediated by tobacco use. [ABSTRACT FROM AUTHOR]