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The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world's adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p

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

BackgroundPregnant people are vulnerable to new or worsening mental health conditions. This study aims to describe prevalence and course of depression and anxiety symptoms in pregnancy during the pre-vaccine COVID-19 pandemic.MethodsThis is a prospective cohort study of pregnant individuals with known or suspected COVID-19. Participants completed Edinburgh Postnatal Depression Scale (EPDS) and Generalized-Anxiety Disorder-7 (GAD-7) questionnaires, screening tools for depression and anxiety, at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum. Prevalence of elevated depressive and anxiety symptoms at each visit was described. Univariable logistic regression analysis was used to determine the association between demographic and clinical factors and those with elevated depression or anxiety symptoms.Results317 participants were included. The prevalence of elevated antepartum depression symptoms was 14.6%, 10.3%, and 20.6% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. The rate of elevated anxiety symptoms was 15.1%, 10.0%, and 17.3% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. A prior history of depression and/or anxiety (p's

Researchers have developed multiple approaches to treat major depressive disorder (MDD). Clinicians commonly employ antidepressant medication (ADM) and psychotherapy as treatment protocols. This review surveys the knowledge and identifies problems with the effects of personality and temperament for MDD treatment in 14 quantitative studies. High extraversion and conscientiousness have a positive effect on psychotherapy treatment while high neuroticism has a negative effect. Agreeableness and openness to experience appear to have conflicting results. All individual traits do not influence ADM treatment except for high and low reward dependence, which may be better for psychotherapy and ADM respectively. Low persistence and high harm avoidance adversely affect psychotherapy, but novelty seeking has an insignificant effect. Some problems in the literature include the self-report measures for individual traits, heterogeneity of study designs, and the complexity of defining personality and temperament. This paper is limited to ADM by SSRIs, SNRIs, and tricyclic antidepressants. These findings may assist patients in choosing treatment types and clinicians in creating better treatment plans for patients, especially psychotherapy. This article may also contribute to the reconceptualization of mental disorders as a dimension instead of a type.

Background: How cognition is influenced by electroconvulsive treatment (ECT) and major depressive disorder (MDD) is still debated. The development and etiology of neurocognitive impairment in MDD were examined by investigating the cognitive profile following ECT related to the state, scar, and trait perspectives, with the former predicting improvements parallel with depressive symptoms, while the two latter expected persisting impairments. Executive functions (EF) and attention are central to cognition and alterations in these functions could influence other domains like memory. The main aims of the present study were to examine the short and long-term effects of ECT on EF and attention in patients with major depressive disorder by exploiting the rapid antidepressant effect of this treatment. Methods: A case-control longitudinal follow-up design was used to investigate the effects of unilateral brief-pulse ECT on EF and attention in patients with depression (n = 36) compared to untreated healthy controls (n = 16). EF and attention were measured pre-treatment, approximately two weeks, and six months post-treatment. Results: The patient group showed significantly worse performance on most tests compared to healthy controls pre-treatment, and no short- or long-term worsening of EF and attention following ECT was found. Significant improvement was identified in patients' attention, processing speed and inhibition after ECT. Conclusions: The present study showed that there was no cognitive worsening after ECT treatment. An improvement in several of the tests measuring inhibition, attention, and processing speed was parallel to symptom reduction, with the former showing associations to symptom change, suggesting state-related effects from improved mood. Still, the patient group performed significantly worse on most measures both pre-treatment and at the short and long-term follow-ups, indicating prevailing trait or scar effects on cognitive functions and potential lack of practice effects. Clinical trial number: NCT04348825 (14.04.20). [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion There are limited reports regarding psychotropic prescriptions in first‐visit patients with major depressive disorder (MDD). The objective of this study is to clarify the prescription patterns of psychotropics and their association with symptoms among first‐visit patients with MDD in Japan.In this cross‐sectional analysis, we examined 376 first‐visit patients diagnosed with MDD. Depressive symptoms were evaluated using the Quick Inventory of Depressive Symptomatology Japanese version (QIDS‐J). To assess personality traits, we administered the Japanese version of the Ten Item Personality Inventory (TIPI‐J), and psychotic symptoms were evaluated using the PRIME Screen‐Revised (PS‐J).Among the first‐visit patients with MDD, 31.4% (118/376) were prescribed antidepressants, and 18.1% (68/376) received benzodiazepines. Overall, 40.2% (151/376) of the patients were prescribed at least one psychotropic medication. In a multivariate logistic regression model using the forced entry method, missing data on educational attainment and the view of myself domain of the QIDS‐J were negatively associated, while the concentration/decision‐making domain of the QIDS‐J was positively associated with antidepressant prescription.More than half of the first‐visit patients did not receive any psychotropic medication. Psychiatrists appear to consider specific symptoms and personality traits when deciding whether to prescribe medications, which may also be influenced by patient preferences. Further studies, including longitudinal analyses, are needed to explore these associations in more detail. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have frequently shown a co-occurrence of psychiatric disorders and Obstructive sleep apnea (OSA), with major depressive disorder (MDD) being a prevalent psychiatric disorder. This study aims to investigate the genetic overlap between MDD and OSA to explore their underlying pathological mechanisms. Methods: Leveraging the extensive and recent GWAS for OSA and MDD, we conducted genetic correlation analyses utilizing Linkage disequilibrium score regression (LDSC), re-evaluated their pleiotropic Single-nucleotide polymorphisms (SNP) with Cross-Phenotype Association (CPASSOC) and Colocalization (COLOC), investigated the overlap at the gene level using physical annotations and Multi-marker Analysis of GenoMic Annotation (MAGMA), and finally employed Mendelian randomization (MR) to assess potential causal relationships between the two disorders. Results: Upon our investigation, we established that MDD and OSA exhibit high heritability (h2MDD=0.02, h2OSA=0.04) alongside a significant genetic correlation (rg=0.31, P= 1.42E-23). Utilizing CPASSOC, we identified 397 pleiotropic SNPs, associable with 45 loci, two of which share common genetic fragments with a pleiotropic role. Furthermore, the MAGMA study uncovered a total of 154 pleiotropic genes capable of influencing multiple brain regions. Lastly, leveraging MR analysis, we concluded that MDD heightens the risk of developing OSA (P=3. 10E-04, OR (95%CI):1.28(1.12~ 1.47)). Conclusion: In summary, our study identified PCLO as a common gene between OSA and MDD and provided evidence that MDD causally contributes to the development of OSA. These insights enhance our understanding of the shared mechanisms underlying the comorbidity of these conditions. [ABSTRACT FROM AUTHOR]

Deep Reinforcement Learning is a branch of artificial intelligence that uses artificial neural networks to model reward-based learning as it occurs in biological agents. Here we modify a Deep Reinforcement Learning approach by imposing a suppressive effect on the connections between neurons in the artificial network—simulating the effect of dendritic spine loss as observed in major depressive disorder (MDD). Surprisingly, this simulated spine loss is sufficient to induce a variety of MDD-like behaviors in the artificially intelligent agent, including anhedonia, increased temporal discounting, avoidance, and an altered exploration/exploitation balance. Furthermore, simulating alternative and longstanding reward-processing-centric conceptions of MDD (dysfunction of the dopamine system, altered reward discounting, context-dependent learning rates, increased exploration) does not produce the same range of MDD-like behaviors. These results support a conceptual model of MDD as a reduction of brain connectivity (and thus information-processing capacity) rather than an imbalance in monoamines—though the computational model suggests a possible explanation for the dysfunction of dopamine systems in MDD. Reversing the spine-loss effect in our computational MDD model can lead to rescue of rewarding behavior under some conditions. This supports the search for treatments that increase plasticity and synaptogenesis, and the model suggests some implications for their effective administration. [ABSTRACT FROM AUTHOR]

This study aimed to explore the physiological dynamics of cognitive stress in patients with Major Depressive Disorder (MDD) and design a multiparametric model for objectively measuring severity of depression. Physiological signal recordings from 40 MDD patients and 40 healthy controls were collected in a baseline stage, in a stress‐inducing stage using two cognitive tests, and in the recovery period. Several features were extracted from electrocardiography, photoplethysmography, electrodermal activity, respiration, and temperature. Differences between values of these features under different conditions were used as indexes of autonomic reactivity and recovery. Finally, a linear model was designed to assess MDD severity, using the Beck Depression Inventory scores as the outcome variable. The performance of this model was assessed using the MDD condition as the response variable. General physiological hyporeactivity and poor recovery from stress predict depression severity across all physiological signals except for respiration. The model to predict depression severity included gender, body mass index, cognitive scores, and mean heart rate recovery, and achieved an accuracy of 78%, a sensitivity of 97% and a specificity of 59%. There is an observed correlation between the behavior of the autonomic nervous system, assessed through physiological signals analysis, and depression severity. Our findings demonstrated that decreased autonomic reactivity and recovery are linked with an increased level of depression. Quantifying the stress response together with a cognitive evaluation and personalization variables may facilitate a more precise diagnosis and monitoring of depression, enabling the tailoring of therapeutic interventions to individual patient needs. [ABSTRACT FROM AUTHOR]

Positive psychology interventions have demonstrated efficacy in treating Major Depressive Disorder (MDD), but the relationship between dispositional optimism and antidepressant treatment response remains unclear. In this study, optimism (Revised Life Orientation Test, LOT-R) and depression severity (Hamilton Depression Rating Scale, HDRS) were assessed in healthy unmedicated MDD participants (N = 86) and healthy controls (N = 65). Treatment response (≥50% reduction in HDRS) was measured in 46 of these MDD participants after 8 weeks of open-label selective serotonin reuptake inhibitor (SSRI) treatment. MDD participants reported significantly lower pre-treatment optimism than healthy controls. Higher pre-treatment optimism, as well as greater increase in optimism (pre-treatment to 8 weeks), were associated with greater likelihood of being an SSRI responder versus non-responder (β = 0.21, p = 0.013; β = 0.32, p = 0.01, respectively), even when ratings of optimism/pessimism were excluded from depression severity/response ratings. The findings are consistent with the importance of aspects of positive psychology in treatment response. Possible mechanisms are discussed. [ABSTRACT FROM AUTHOR]

Objective: An alternative metric for evaluating insulin resistance (IR) is the triglyceride glucose-body mass index (TyG-BMI). However, it is yet unclear how TyG-BMI and suicide attempts (SA) are related. The objective of this research was to explore the correlation between the TyG-BMI index and SA in individuals with untreated first-episode (UFE) major depressive disorder (MDD) in Shanxi Province. Methods: This cross-sectional study was conducted from September 2016 to December 2018 in the psychiatric outpatient clinic of Taiyuan General Hospital and included 1718 patients with UFE MDD, with a mean age of 34.9 ± 12.4 years. The relationship between TyG-BMI and SA was assessed using logistic regression modeling. We investigated threshold effects using a two-piecewise linear regression model. Results: Taking into consideration the potential influence of confounding variables, a comprehensive multivariate logistic regression analysis was conducted, which demonstrated the absence of a statistically significant association between the TyG-BMI index and the occurrence of SA, as evidenced by P-values that were all greater than 0.05. On the other hand, the visual analysis of the smoothed plots revealed a U-shaped relationship between the TyG-BMI index and the incidence of SA, with a notable inflection occurring at a TyG-BMI value of around 210. It was observed that the effect sizes flanking the inflection point, accompanied by their 95% confidence intervals, were 0.985 (95% CI: 0.972 to 0.999, P = 0.031) and 1.012 (95% CI: 1.003 to 1.047, P = 0.005), respectively. Conclusions: In UFE MDD patients, a U-shaped link was observed between TyG-BMI and SA, with the minimal SA incidence noted at a TyG-BMI level of 210, signifying that an augmented risk for SA might be connected to both diminished and augmented TyG-BMI levels. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMaterials and methodsResultsConclusions\nHIGHLIGHTSThis study aimed to provide a comprehensive synthesis of the evidence examining lipid profiles in drug-naïve MDD patients.We searched PubMed, Scopus, and ISI Web of Science up to August 2023 for total cholesterol, HDL-C, LDL-C, and triglyceride levels in drug-naïve MDD patients.A total of 17 articles comprising 2174 individuals including drug-naïve MDD subjects and controls were included. Our results showed that concentrations of total cholesterol were lower in drug-naïve MDD patients compared with healthy controls (SMD −0.49, 95% CI −0.881 to −0.105; p = 0.015; I2 = 90.6%). However, comparison of other lipid levels between MDD patients and healthy controls demonstrated no significant difference. The results revealed that the association of total cholesterol levels with MDD is more prominent in male-dominant studies (SMD −1.20, 95% CI −2.23 to −0.18, I2 = 87.9%) than in female-dominant studies (SMD −0.25, 95% CI −0.63–0.13, I2 = 89.0%). In meta-regression, none of the factors including year of publication, Newcastle-Ottawa Scale score, sample size, BMI, and mean age of participants had a significant influence on the association between cholesterol levels and MDD.Lower levels of total cholesterol, especially in males, are associated with MDD, so early lipid monitoring and targeted interventions are necessary.This study aimed to provide a comprehensive synthesis of the evidence examining lipid profiles in drug-naïve MDD patients.We searched PubMed, Scopus, and ISI Web of Science until August 2023 for total cholesterol, HDL-C, LDL-C, and triglyceride levels in drug-naïve MDD patients.Our results showed that concentrations of total cholesterol were lower in drug-naïve MDD patients than in healthy controls and no significant difference in other lipid levels.Lower levels of total cholesterol, especially in males, are associated with MDD, so early lipid monitoring and targeted interventions are necessary.This study aimed to provide a comprehensive synthesis of the evidence examining lipid profiles in drug-naïve MDD patients.We searched PubMed, Scopus, and ISI Web of Science until August 2023 for total cholesterol, HDL-C, LDL-C, and triglyceride levels in drug-naïve MDD patients.Our results showed that concentrations of total cholesterol were lower in drug-naïve MDD patients than in healthy controls and no significant difference in other lipid levels.Lower levels of total cholesterol, especially in males, are associated with MDD, so early lipid monitoring and targeted interventions are necessary. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) represents a sizable economic burden in Spain. Pharmacogenetic (PGx) screening to guide the choice of antidepressant medication (ADM) in MDD patients yields higher response and remission rates, which could reduce both healthcare and indirect costs. We built a cost-effectiveness probabilistic Markov model with microsimulation using Tree Age Pro 2022, simulating a patient cohort from the SNHS starting ADM for MDD, and comparing PGx screening before starting ADM versus no screening (No PGx). We carried out a probabilistic sensitivity analysis using the Monte Carlo simulation with microsimulation, set for 1000 iterations and 1000 microsimulation trials, both from societal and healthcare provider perspectives, for a time horizon of 3 years. From a societal perspective, the model estimated a mean cost of 3172.85€ and effectiveness of 2.64 quality-adjusted life years (QALYs) for the No PGx strategy, and a mean cost of 1687.02€ and effectiveness of 2.84 QALYs for the PGx strategy. The mean ICER was −7820.56 €/QALY. From a healthcare provider perspective (no indirect costs considered), the mean cost was 662.62€ for the No PGx strategy, and 446.60€ for the PGx strategy. The mean ICER was −1130.16 €/QALY. The heterogeneity of input data from the literature, the need for assumptions of homogeneous distribution of variables and events across population and time, and the inherent limitations of cost-effectiveness analysis should be considered. The model omits combined therapies (ADMs with mood stabilizers, antipsychotics, cognitive behavioral therapy...). PGx screening in MDD prior to ADM start is a dominant strategy in the SNHS. • Treatment failure rates in major depressive disorder are high and contribute to its economic impact • Pharmacogenetics-guided choice of antidepressants lower failure rates, which could reduce the associated economic burden • We analyzed the cost-effectiveness of this strategy with a Markov model • Microsimulation allows for a more accurate simulation of individual patients' characteristics • Pharmacogenetic screening when starting antidepressants is a dominant strategy [ABSTRACT FROM AUTHOR]

The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions. Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7–65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed. Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA. The sample size is small. MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity. [Display omitted] • Compared to healthy controls, the normal ACTH MDD patients had higher Glx and lower GSH levels • Glx and GSH levels were inversely related to MDD severity • In the high ACTH MDD group, Glx positively correlated with delayed memory, and GSH with abstraction • Neurochemical differences in MDD patients' brains at varying HPA axis levels are linked to MDD severity and cognitive function [ABSTRACT FROM AUTHOR]

Psychomotor retardation (PMR) is a core feature of major depressive disorder (MDD), which is characterized by abnormalities in motor control and cognitive processes. PMR in MDD can predict a poor antidepressant response, suggesting that PMR may serve as a marker of the antidepressant response. However, the neuropathological relationship between treatment outcomes and PMR remains uncertain. Thus, this study examined electrophysiological biomarkers associated with poor antidepressant response in MDD. A total of 142 subjects were enrolled in this study, including 49 healthy controls (HCs) and 93 MDD patients. All participants performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. Patients who exhibited at least a 50 % reduction in disorder severity at the endpoint (>2 weeks) were considered to be responders. Motor-related beta desynchronization (MRBD) and inter- and intra-hemispheric functional connectivity were measured in the bilateral motor network. An increased MRBD and decreased inter- and intra-hemispheric functional connectivity in the motor network during movement were observed in non-responders, relative to responders and HCs. This dysregulation predicted the potential antidepressant response. Abnormal local activity and functional connectivity in the motor network indicate poor psychomotor function, which might cause insensitivity to antidepressant treatment. This could be regarded as a potential neural mechanism for the prediction of a patient's treatment response. • MDD patients with poor antidepressant response have increased MRBD. • MDD patients with poor antidepressant response have decreased inter- and intra-hemispheric functional connectivity in the motor network. [ABSTRACT FROM AUTHOR]

According to biopsychosocial models, experiencing parental child abuse increases susceptibility to adulthood psychopathology. However, there is a paucity of studies examining potential mechanisms of the parental child abuse and adulthood psychopathology relationship. The purpose of the current study was to determine if Time 2 (T2) trait self-esteem mediated levels of Time 1 (T1) retrospectively recalled parental child abuse predicting (T3) past-year major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD), alcohol use disorder (AUD), and substance use disorder (SUD) symptoms. The 18-year Midlife Development in the United States (MIDUS) study included participants (N = 3294; T1 average age of 45.62 years) assessed at three different time points, each spaced about nine years apart. We performed structural equation mediation modeling analyses to determine how maternal and paternal child abuse at T1 would independently predict T3 MDD, GAD, PD, AUD, and SUD symptoms. We also examined whether T2 self-esteem mediated these relations while controlling for adulthood T1 psychopathology symptoms, demographics, socioeconomic status, somatic symptoms, and parental psychopathology. Consistent with our hypotheses, higher T1 maternal and paternal abuse predicted increased T3 GAD, PD, AUD, and SUD symptoms via diminished T2 self-esteem as the mediator (% proportion mediated = 33.0–100). However, childhood paternal, but not maternal, abuse predicted adulthood MDD symptoms via reduced self-esteem. Findings remained after adjusting for covariates. Our research highlights the importance of understanding retrospectively recalled parental child abuse–adulthood psychopathology relations, their potential mechanisms, and self-esteem as a malleable treatment target for adults with heightened child abuse. • T1 parental abuse predicted higher T3 adult psychopathology via lower self-esteem. • SEM analyses showed that these mediational processes occurred across 18 years. • Past-year MDD, GAD, PD, AUD, and SUD symptoms at T3 were measured. • Paternal abuse, not maternal, predicted adult MDD via low self-esteem. • Findings stayed similar after adjusting for demographic, SES, and somatic variables. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) may exhibit impairments in cognitive flexibility. This study investigated whether the cognitive flexibility deficits in MDD are evident across general stimuli or specific to emotional stimuli, while exploring the underlying neuropsychological mechanism. A total of 41 MDD patients and 42 healthy controls (HCs) were recruited. Event-related potentials (ERPs) were recorded when participants performed a non-emotional and an emotional task switching paradigm (N-ETSP and ETSP), both of which assessed cognitive flexibility. Microstate and source localization analysis were applied to reflect brain activity among different brain areas during task switching. In the N-ETSP, MDD group showed larger P3 difference wave (Pd3) amplitudes and longer P2 difference wave (Pd2) latencies. In the ETSP, MDD group displayed smaller N2 difference wave (Nd2) amplitudes and larger Pd3 amplitudes. The comparison of sLORETA images of emotional switch task and emotional repeat task showed that MDD group had increased activation in the precentral gyrus in microstate2 of the P2 time window and had reduced activation in the middle occipital gyrus in microstate3 of the N2 time window. The cross-sectional design failed to capture dynamic changes in cognitive flexibility in MDD. MDD demonstrated impaired cognitive flexibility respond to both non-emotional and emotional stimuli, with greater impairment for negative emotional stimuli. These deficits are evident in abnormal ERPs component during the early attention stage and the later task preparation stage. Furthermore, abnormal emotional switching cost in MDD appears to be related to early abnormal perceptual control in the parietal-occipital cortex. • MDD exhibited impaired cognitive flexibility in general and negative stimuli. • Higher emotional switching cost of error rate, the lower brain activation in MDD. • MDD showed the abnormal early perceptual control in the parietal-occipital cortex. [ABSTRACT FROM AUTHOR]

Observational studies have shown that individual sleep traits habits are potential risk factors for major depression. However, it is not known whether there is a causal relationship between individual sleep traits habits such as continuous sleep duration, short sleep duration, short sleep duration, insomnia, nap during the day, snoring, and major depression. In this study, Mendelian randomization (MR) was used to predict major depressive disorder (MDD) in individuals sleep traits habits. Data were obtained from the genome-wide association study (GWAS). Nine MR analysis methods were used: Inverse Variance Weighted (IVW) [fixed effects/multiplicative random effects], simple mode, simple mode, weighted mode, simple median, weighted median, penalised weighted median, and MR-Egger, MR Egger (bootstrap). IVW was used as the main analysis method for the MR analysis of two samples, and the other methods were used as supplements. The results obtained through the IVW method supported a causal relationship between sleep duration and decreased risk of MDD (odds ratio, OR ivw : 0.998; 95 % CI: 0.996–0.999, P<0.001). Two-Sample MR, results showed that short sleep duration has a causal effect on the increased risk of MDD (odds ratio, OR ivw : 1.179; 95 % CI: 1.108–1.255, P<0.001). However, there were no sufficient evidence supported that long sleep duration has a causal effect on the decreased risk of MDD (odds ratio, OR ivw : 0.991; 95 % CI: 0.924–1.062, P = 0.793). A significant causal relationship between insomnia and increased risk of MDD was observed (OR: 1.233; 95 % CI: 1.214–1.253, P<0.001). Interestingly, our study also found that daytime napping has a causal effect on the increased risk of MDD (odds ratio, OR ivw : 1.519; 95 % CI: 1.376–1.678, P<0.001). The present results did not show a significant causal relationship between snoring and the risk of MDD (OR ivw : 1.000; 95 % CI: 0.998–1.002, P = 0.906). Obstructive sleep apnea (odds ratio, OR ivw : 1.021; 95 % CI: 0.972–1.072, P = 0.407) and morning person (odds ratio, OR ivw : 1.021; 95 % CI: 0.972–1.072, P = 0.407) have no causal effect on the increased risk of MDD. The study could not ascertain whether there were genetic differences among different ethnicities, nations, and regions, as it only included participants of European ancestry. In summary, our research provides genetic evidence for the relationship between individual sleep traits (short sleep duration, insomnia, daytime napping) and the increased risk of MDD. Interventions targeting lifestyle factors may reduce the risk of MDD. • This study explored the causality between lifestyle and major depressive disorder by Mendelian Randomization analysis. • This research provides genetic evidence supporting that sleep traits increase major depressive disorder risk. • The research primarily included European ancestry. The conclusions may not apply to other ethnic and regional groups. [ABSTRACT FROM AUTHOR]

Rs768705 (TMEM161B) is one of the identified single nucleotide polymorphisms related to major depressive disorder (MDD). Paranoid personality traits are independently associated with the risk of MDD. This study aimed to investigate the interaction effect between rs768705 (TMEM161B) and paranoid personality traits on the new-onset risk of MDD in Chinese freshmen. A longitudinal study was conducted among 7642 Chinese freshmen without lifetime MDD at baseline in 2018. 158 new-onset MDD cases were ascertained in 2019. DNA samples were extracted to detect the genotype of rs768705. The diagnostic and statistical manual of mental disorders-IV criteria were used to determine MDD and personality disorder traits. Multiplicative interaction was assessed by logistic regression models. Tomas Andersson's method for calculating biological interactions was used to estimate the additive interaction. Rs768705(AG) (OR = 1.88, 95 % CI: 1.24–2.83) and paranoid personality traits (OR = 3.68, 95 % CI: 2.57–5.26) were significantly associated with the risk of MDD. The multiplicative interaction model with the product term of rs768705 and paranoid personality trait traits had a significant interaction effect (OR = 4.20, 95 % CI:1.62–10.91). There was also a significant additive interaction effect (RR = 7.08, 95 % CI:4.31–11.65) for the incidence of MDD. Seventy seven percent patients among new MDD cases were attributed to the additive interaction effect between rs768705 and paranoid personality traits. Rs768705 (AG) may interact with paranoid personality traits to increase the incidence of MDD among Chinese college students. Schools and psychosocial health organizations should pay more attention to individuals with paranoid personality traits for MDD intervention and prevention. • This was a 1-year longitudinal study conducted among 7642 Chinese freshmen. • There was an addictive interaction effect between rs768705 (AG) and paranoid personality traits on occurrence of MDD. • 77% of new MDD patients were attributed to the interaction effect of rs768705 (AG) & paranoid personality traits. [ABSTRACT FROM AUTHOR]

Treatable mental disorders, such as psychotic, major depressive disorder (MDD), and bipolar disorder (BD), contribute to a substantial portion of suicide risk, often accompanied by neurocognitive deficits. We report the association between cognitive function and suicidal ideation/suicide attempts (SI/SA) in individuals with schizoaffective disorder, BD, and MDD. A systematic search was conducted on PubMed, Ovid and Scopus databases for primary studies published from inception to April 2024. Eligible articles that reported on the effect size of association between cognition and SI/SA were pooled using a random effects model. A total of 41 studies were included for analysis. There was a negative association between executive functioning and SI/SA in schizoaffective disorder (SA: Corr = −0·78, 95 % CI [−1·00, 0·98]; SI: Corr = −0·06, 95 % CI [−0·85, 0·82]) and MDD (SA: Corr = −0·227, 95 % CI [−0·419, −0·017]; SI: Corr = −0·14, 95 % CI [−0·33, 0·06]). Results were mixed for BD, with a significant positive association between SA and global executive functioning (Corr = 0·08, 95 % CI [0·01, 0·15]) and negative association with emotion inhibition. Mixed results were observed for processing speed, attention, and learning and memory, transdiagnostically. There is heterogeneity across sample compositions and cognitive measures. We did not have detailed information on individuals with respect to demographics and comorbidities. We observed a transdiagnostic association between measures of cognitive functions and aspects of suicidality. The interplay of cognitive disturbances, particularly in reward-based functioning, may underlie suicidality in individuals with mental disorders. Disturbances in impulse control, planning, and working memory may contribute to self-injurious behavior and suicide. • Suicide attempt (SA) was associated with executive functioning in bipolar disorder. • SA was negatively associated with emotion inhibition in bipolar disorder. • Mixed findings were observed for attention and processing speed transdiagnostically. • Suicidal ideation (SI) was associated with executive functioning in schizophrenia. • SI was associated with executive functioning in major depressive disorder. [ABSTRACT FROM AUTHOR]

Both low vagally-mediated heart rate variability (HRV) and depression have been shown to be risk factors for cardiovascular disease (CVD). We recently identified an HRV cutpoint below which persons have an increased risk for several cardiometabolic disorders. However, no cutpoint exists to identify those at risk for depression. The association between daytime HRV and diagnostically validated depression cutoffs using the five-item World Health Organization Well-being Index (WHO-5) was examined in adults from the Mannheim Industrial Cohort Study (n = 9973; M age = 41.9[10.9]; 20 % women [ n = 1934]). The aim was to identify HRV cutpoints for individuals who may have clinical depression. Regression adjusting for age, sex, and linear trend showed a significant quadratic association between depression, indexed by WHO-5 scores and HRV, indexed by the root mean square successive differences (RMSSD) in milliseconds (ms) (p < 0.001). Logistic regression models adjusting for age, sex, and heart period (i.e., inter-beat intervals) compared the clinically depressed (WHO-5 ≤ 28) and those with a screening diagnosis of depression (WHO-5 ≤ 50) to the rest of the population. Significant odds ratios suggested two RMSSD values 25 ± 2 ms (OR = 1.39 [1.17, 1.64]) and 35 ± 2 ms (OR = 1.17 [1.02, 1.34]) that may be used to identify those with an elevated risk for depression. The sample was primarily German men. Fitness and anti-depressant use were not available. As HRV is a brief measure that can be used in clinical settings, our HRV cutpoints have implications for the early detection of those at risk for psychological and cardiometabolic disorders. • Major depressive disorder is among the most globally prevalent illnesses. • Early identification can reduce disease burden. • We found cutpoints for a physiological marker of depression using heart rate variability. • These clinical cutpoints can be used in primary care settings. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a widespread mental health issue, impacting spatial and temporal aspects of brain activity. The neural mechanisms behind MDD remain unclear. To address this gap, we introduce a novel measure, spatiotemporal topology (SPT), capturing both the hierarchy and dynamic attributes of brain activity in depressive disorder patients. We analyzed fMRI data from 285 MDD inpatients and 141 healthy controls (HC). SPT was assessed by coupling brain gradient measurement and time delay estimation. A nested machine learning process distinguished between MDD and HC using SPT. Person's correlation tested the link between SPT's and symptom severity, and another machine learning method predicted the gap between patients' chronological and brain age. SPT demonstrated significant differences between patients and healthy controls (F = 2.944, p < 0.001). Machine learning approaches revealed SPT's ability to discriminate between patients and healthy controls (Accuracy = 0.65, Sensitivity = 0.67, Specificity = 0.64). Moreover, SPT correlated with the severity of depression symptom (r = 0.32. p FDR = 0.045) and predicted the gap between patients' chronological age and brain age (r = 0.756, p < 0.001). Evaluation of brain dynamics was constrained by MRI temporal resolution. Our study introduces SPT as a promising metric to characterize the spatiotemporal signature of brain function, providing insights into deviant brain activity associated with depressive disorders and advancing our understanding of their psychopathological mechanisms. • Spatial and temporal brain aberrations linked to Major Depressive Disorder (MDD). • SPT integrates spatial and temporal features as a potential MDD biomarker. • SPT effectively discriminates between MDD and healthy populations via machine learning. • SPT correlates with depression severity and predicts differences in brain-age predictions. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs). Sixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment. Patients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = −0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases. The current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined. Using a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression. • Patients with Major Depressive Disorder (MDD) showed reduced inter-hemispheric functional connectivity (HoFC) in the medial amygdala compared to healthy controls. • HoFC in the medial amygdala was correlated with the severity of depression symptoms and emotional processing performance. • Baseline HoFC levels in the medial amygdala modestly predicted the response to Serotonin Selective Reuptake Inhibitors (SSRIs) after 2 months of treatment. • The findings emphasize the role of interhemispheric communication within amygdalar sub-regions in understanding depression. [ABSTRACT FROM AUTHOR]

Research in functional asymmetry of Major Depressive Disorder (MDD) under different tasks is crucial for clinical diagnose. Fifty individuals with MDD and twenty healthy controls (HCS) were recruited for hemodynamic data collection under four fNIRS tasks (Emotional picture, Verbal fluency, Fingering and Negative emotional picture description task). Integral values and functional connectivity strength were employed to probe neural activation and functional connectivity in frontal and temporal lobes in MDD. Following, asymmetry characteristic of the frontal cortex between MDD and HCS under four tasks were carefully analyzed and compared. Individuals with MDD demonstrated heightened connectivity between the frontal and right temporal lobes and reduced connectivity between the frontal and left temporal lobes compared to HCS in all tasks. Additionally, MDD exhibited attenuated activation in the left frontal lobes and exaggerated activation in the right frontal lobes, diverging from HCS. Furthermore, the disparities in left-right asymmetry characteristic of frontal cortex activation between MDD and HCS were more pronounced during the combined task. Further research is required to grasp the neurophysiological mechanisms governing left-right asymmetry across various tasks and the influence of task-induced brain fatigue on cerebral cortex hemodynamics in MDD. The left-right asymmetry feature provides valuable neurophysiological insights for diagnosing MDD clinically. Variations in activation patterns and functional connectivity features between MDD and HCS are closely tied to the task chosen. Thus, in clinical practice, carefully selecting appropriate fNIRS tasks and relevant features can significantly improve the diagnostic accuracy of MDD. • Activation and functional connectivity of MDD under four fNIRS tasks were investigated. • A left-right asymmetry characteristics of frontal cortex was proposed to characterize MDD patients. • Task related characteristics for MDD patients were carefully compared and discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • A RCT study to investigate the efficacy of abdominal acupuncture for MDD patients. • Acupuncture can treat MDD by regulating the integration of functional networks. • It's the first time provided a marker to predict the efficacy of acupuncture. Abdominal acupuncture has definite efficacy for major depressive disorder (MDD). Our study examined how abdominal acupuncture regulates the integration within and between brain networks of MDD patients by neuroimaging and whether this functional integration can predict the efficacy. Forty-six female MDD patients were randomly divided into a fluoxetine + real acupuncture group (n = 22) and a fluoxetine + sham acupuncture group (n = 24). The differences in functional magnetic resonance imaging data in the intra- and inter-network functional connectivity (FC) of the default mode network (DMN), affective network (AN), salience network (SN), and cognitive control network (CCN) between the two groups were analyzed. The FCs in brain regions with the inter-group differences and support vector regression were used to predict the efficacy of abdominal acupuncture. Our results showed: that the intra- and inter-network FCs of DMN, AN, SN, and CCN could be changed by abdominal acupuncture. Using the baseline FCs within AN and DMN or AN–DMN as characteristics, combined with support vector regression, could better predict the efficacy of acupuncture. Our study suggests that abdominal acupuncture could treat MDD by regulating the integration of the functional networks DMN, AN, SN, and CCN. The baseline FCs within the DMN and AN or between them could be used as neural markers for predicting the efficacy of abdominal acupuncture. [ABSTRACT FROM AUTHOR]

• ・Glucocorticoids induced HMGB1 release in primary cultured microglia but not in neuron. • ・Dexamethasone-BSA, a membrane-impermeable GR agonist induced HMGB1 release. • ・Glucocorticoids triggered translocation of HMGB1 from nuclear to cytosol. Stress, a risk factor for major depressive disorder and Alzheimer disease, leads to the release of high-mobility group box-1 (HMGB1) protein, which in turn causes neuroinflammation. The mechanism underlying stress-induced HMGB1 release is unknown, but stress-associated glucocorticoids could be involved. Primary cultured rat cortical microglia and neurons were treated with corticosterone, a stress-associated glucocorticoid, and HMGB1 release was measured by ELISA and western blotting to test this hypothesis. With corticosterone treatment, significant HMGB1 was released in microglia but not in neuronal cell cultures. HMGB1 mRNA expression and HMGB1 protein expression in microglia were not affected by corticosterone treatment. Thus, the source of extracellular HMGB1 released into the medium is likely to be existing nuclear HMGB1 rather than newly synthesized HMGB1. Corticosterone-induced HMGB1 release in microglia culture was significantly attenuated by blocking glucocorticoid receptors but not mineralocorticoid receptors. Dexamethasone, a selective glucocorticoid receptor agonist, and dexamethasone-bovine serum albumin (BSA), a membrane-impermeable glucocorticoid receptor agonist used to confirm the membrane receptor-mediated effects of glucocorticoids, increased the release of HMGB1. Immunocytochemistry showed that HMGB1 translocated from the nucleus to the cytoplasm following dexamethasone or dexamethasone-BSA treatment through glucocorticoid receptors. The present findings suggest that glucocorticoids stimulate microglial membrane glucocorticoid receptors and trigger cytoplasmic translocation and extracellular release of nuclear HMGB1. Thus, under stress conditions, glucocorticoids induce microglial HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders. [ABSTRACT FROM AUTHOR]

• Epigenetics played a crucial role in depression with suicide ideation (DSI). • Epigenetic molecules related to DSI interacted with each other. • Peripheral epigenetic molecules were potential suicidal biomarkers for DSI. Suicide ideation (SI) is the major cause of death in persons with depression, whereas effective and accurate biomarkers for suicidal behavior of persons with depression are still lack. Recently, manifold studies in vivo revealed that epigenetic alterations including DNA methylation, non-coding RNA regulation, RNA editing and histone modification, were associated with depressive severity and SI, and peripheral epigenetic molecules may be potential biomarkers for suicidal risk of persons with depression. Therefore, we firstly reviewed recent epigenetic advancements in depression with suicide ideation (DSI) according to studies based on human tissue. Furthermore, we discussed the significance and potential of minimally-invasive peripheral epigenetic molecules to identify potential suicidal biomarkers for DSI, aiming to promote early identification and therapeutic evaluation of DSI. [ABSTRACT FROM AUTHOR]

[Display omitted] • MOE ameliorates depressive behaviors by modulating the microbiota-gut-brain axis. • MOE restored sucrose preference in depressed mice. • MOE reversed CUMS-induced 5-HT reduction in the prefrontal cortex and hippocampus. • MOE increased gut lactobacilli in stressed mice. The gut microbiota has been posited as a target for the treatment of major depressive disorder. Herein, we investigated the effect of the hydroethanolic leaf extract of Mallotus oppositifolius (MOE) on the gut microbiota of mice and how this contributes to its known antidepressant-like effect. A 6-week chronic unpredictable mild stress (CUMS) procedure was employed in 7 groups of mice to induce depression. From the third week, oral MOE treatments (10, 30, 100 mg/kg) and two reference drugs, fluoxetine (12 mg/kg) and minocycline (40 mg/kg), known to affect the gut microbiota, were administered. The sixth and seventh groups were the vehicle stressed (VEH-S) and non-stressed groups (VEH-NS). Changes in depressive-like behaviors were assessed using sucrose preference test while the forced swimming test (FST) was used to assess sustained antidepressant-effect after treatment discontinuation. Moreover, changes in prefrontal cortex (PFC) and hippocampal serotonin (5-HT) levels were evaluated using enzyme-linked immunosorbent assay (ELISA). The effect of treatment on the profile of the gut microbiota of the groups was elucidated using 16S rRNA Oxford Nanopore sequencing. MOE and reference drugs reversed the depression-associated reduction in sucrose preference when compared to VEH-S. MOE (with peak effect at 30 mg/kg) reduced immobility while increasing swimming and climbing behaviors. MOE reversed CUMS-induced reduction of 5-HT concentration in PFC and hippocampus. The behavioral effects of MOE were associated with shifts in the gut microbiota of CUMS-exposed mice. The study has provided seminal evidence that MOE ameliorates CUMS-induced depressive symptoms by modulating gut microbiota and increasing brain 5-HT levels. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods: We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients' blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results: The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion: TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear. Methods: This study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery. Results: Multivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes. Conclusion: Thus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study. [ABSTRACT FROM AUTHOR]

Introduction: Gender- and age-specific research on medications is essential for personalizing treatment plans, optimizing dosing, minimizing adverse effects and improving outcomes. Women are twice as likely to be diagnosed with major depressive disorder (MDD), and it is commonly reported during their reproductive years. This post-hoc pooled analysis evaluated the efficacy of sertraline (one of the most studied medications in women) in women of reproductive age (18–44 years). Methods: Data was pooled from nine clinical trials of sertraline that included 1832 subjects with MDD. The analysis set included 1097 women, 651 of those were of reproductive age. Sertraline was compared with placebo for changes in total HAM-D17 and CGI scores measured over time through MMRM analysis. The change from baseline to the end of study (-week 8) was assessed using ANCOVA. Results: The changes from baseline in total HAM-D17 and CGI scores were significantly higher for sertraline than for placebo at the end of 8 weeks for all women (LS Mean difference, 95% CI: -1.81(-3.01,-0.62), P = 0.0029; -0.38(-0.55,-0.20), P < 0.0001, respectively). For women of reproductive age these changes (LS Mean difference, 95% CI: -2.08(-3.52,-0.64), P = 0.0047; -0.44(-0.66,-0.22), P < 0.0001, respectively), were significant from week 2 (HAM-D17) and week 1 (CGI) till the end of study. Limitations: Only sertraline and placebo arms were included in the analysis. The dosing varied between studies, and the effect of dose was not addressed. Conclusions: Sertraline is an effective option for treatment of MDD in women, including those in the childbearing age. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to assess the prevalence and associated factors of major depressive disorder (MDD), generalized anxiety disorder (GAD), and past 12-month suicidal behaviour (PSB) among adolescents in Mozambique. Methods: Data from 3,109 females (aged 15–19 years) and 1,439 males (aged 15–19 years) that participated in the 2022-23 Mozambique Demographic and health Survey were analysed. MDD was assessed with the PHQ-9 and GAD with the GAD-7. Results: Results indicate that among girls the prevalence of PSB was 4.3% (attempt 1.0%, plan 1.9% and/or ideation 3.6%) and among boys 2.5% (attempt 0.3%, plan 0.7% and/or ideation 2.4%). Among girls and boys, the prevalence of MDD (≥ 8 scores) was 15.5% and 3.7%, respectively, and the prevalence of GAD (≥ 5 scores) was 25.0% and 10.3%, respectively. In adjusted logistic regression analysis, among girls, GAD was positively and solid fuel use was negatively associated with PSB, while among boys MDD and urban residence were positively associated with PSB. Among female adolescents, currently being pregnant and "big problem to get money for medical treatment" increased the odds of MDD. While among male adolescents, urban residence, having a genital sore or ulcer, has living children, and early sexual debut were positively associated with MDD. Urban residence, current alcohol use, and early sexual debut were positively associated with GAD in male adolescents, while poorer wealth status, being pregnant, and having a "big problem to get money for medical treatment" were positively associated with GAD in female adolescents. Conclusion: About 3% of participants had PSB, among girls one in five had MDD or GAD and among boys more than 5% had MDD or GAD. Public health interventions can be guided by several associated factors that have been identified. [ABSTRACT FROM AUTHOR]

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multi-center collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders. [ABSTRACT FROM AUTHOR]

Objective: Limited research exists on the use of electroconvulsive therapy (ECT) for adolescents with major depressive disorder (MDD). This study investigates the effects of ECT on inflammatory markers in adolescents aged 13-18 suffering from severe MDD, evaluating its efficacy in modulating cellular inflammatory markers and ameliorating depressive symptoms. Methods: A cohort of 38 adolescents with severe MDD received standard antidepressant therapy along with 6-8 ECT sessions spanning two weeks. A control group of 29 age-matched, healthy individuals was also assessed for comparative purposes. The investigation measured variations in depressive symptomatology and inflammatory marker levels (IL-1β, IL-6, IL-10) pre- and post-intervention. Results: Post-ECT, a substantial decrease in pro-inflammatory cytokines (IL-1β and IL-6) and an increase in the anti-inflammatory cytokine (IL-10) were noted. Participants who responded to the treatment showed a significant decline in HAMD-17 scores, which accentuates ECT's therapeutic potential. Comparative analysis indicated a significant correlation between post-treatment inflammatory marker alterations and clinical improvement, implying that shifts in inflammatory state might serve as predictors of treatment response. Moreover, the mitigation of depressive symptoms exhibited a moderate correlation with post-treatment decrements in IL-1β and IL-6 levels, underscoring MDD's intricacy and ECT's comprehensive impact. Conclusion: While initial inflammatory marker levels did not predict the response to ECT, the post-treatment measures appeared to be linked to clinical improvement. These findings suggest ECT's potential effectiveness in treating severe MDD in adolescents and point to the possible predictive value of inflammatory markers in therapeutic outcomes. The study contributes to our understanding of the biopsychosocial framework of MDD and indicates that ECT may be a viable treatment option for this population. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD). Methods: A systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs). Results: Five RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2–13%) and the control group (4–21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache. Conclusion: Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is a common mental disease that significantly impact the daily lives of those affected. Acupuncture has shown promising therapeutic effects in the treatment of MDD, but its underlying mechanisms remain unclear. This study aims to evaluate the influence of acupuncture on the brain function of patients with MDD and it's therapeutic effects on MDD. Methods: This study plans to recruit 112 participants, who will be randomly allocated to either the acupuncture group or the sham acupuncture group in a 1:1 ratio. Both groups will undergo 8 weeks of treatment, consisting of three sessions per week, with each session lasting for 30 min. A follow-up period of 3 months will be conducted after the treatment. Assessments will be conducted at weeks 0, 8, 12, 16, and 20 in this study. The primary outcome measure will be functional near-infrared spectroscopy (fNIRS) brain imaging, while secondary outcome measures will include Beck Depression Inventory II (BDI-II), Self-Rating Anxiety Scale (SAS), 36-Item Short Form Survey Instrument (SF-36), Traditional Chinese Medicine (TCM) syndrome score scale, and symptom elimination rate. Discussion: While acupuncture has been confirmed to have a certain degree of therapeutic efficacy in the treatment of MDD, research on the mechanisms underlying acupuncture's treatment of MDD remains limited, particularly with regards to its impact on the brain function of individuals with MDD. This study aims to explore both the clinical effectiveness and treatment mechanisms of acupuncture for MDD, with a specific focus on its influence on brain function. This research endeavors to provide new insights into the potential of acupuncture as a therapeutic approach for the treatment of MDD in the future. Trial Registration: www.chictr.org.cn, ID: ChiCTR2300076292. Registered on 28 September 2023. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate the level of knowledge of primary care physicians in Lambayeque, Peru, regarding the diagnosis and treatment of Major Depressive Disorder. Methods: A cross-sectional analytical study was conducted among 106 primary care physicians in Lambayeque, Peru. Data were collected using a validated questionnaire assessing Major Depressive Disorder diagnosis and treatment knowledge. Physicians' knowledge levels were categorized as inadequate, adequate, or excellent. Poisson regression models were employed to identify factors associated with adequate knowledge. Results: The response rate was 81.21%. Only 36.79% of physicians demonstrated adequate knowledge, with none achieving excellent knowledge. The median score was 6 (IQR: 5-7). Mental health training, which may reflect the new law's implementation, was significantly associated with higher knowledge levels (PR: 2.42, 95% CI: 1.02 to 5.10). Other factors were not significantly associated with knowledge levels. Conclusions: The proportion of primary care physicians with adequate Major Depressive Disorder knowledge has doubled since 2014, indicating a positive effect of the mental health law. However, to increase this number, continuous professional development programs are needed. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). Methods: We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center's cohort. Results: We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. Conclusions: Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment (CM) is closely linked to internet addiction (IA), especially in adolescents with Major Depressive Disorder (MDD). Previous studies have shown that adolescents who experience CM are more likely to develop IA and other psychological problems. This study aims to explore the complex relationship between CM and IA through network analysis, particularly identifying the core symptoms and bridge symptoms to better understand the development of IA in these adolescents. Methods: A cross-sectional study was conducted in seven hospitals in Anhui Province, China, involving 332 adolescents diagnosed with MDD using DSM-5 criteria. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Internet Addiction Test (IAT) were used to assess CM and IA symptoms, respectively. Gender-based network analysis was also performed. Results: Network analysis constructed a CM-IA network and identified core and bridge symptoms. "Depress/moody/nervous being offline", "Request an extension for longer time", "Sleep loss due to late-night logins", and "emotional abuse" emerged as central symptoms within the CM-IA network. Additionally, "emotional abuse", "sexual abuse", and "complaints about online time" were identified as key bridge symptoms linking CM and IA. These symptoms demonstrated significant connectivity, underscoring their critical role in linking CM and IA. Conclusion: The findings highlight the complex relationship between CM and IA in adolescents with MDD. Specific symptoms, such as emotional abuse and online-related symptoms, play important roles in understanding and intervening in adolescent IA. Future interventions should target these core and bridge symptoms for more effective prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Empathy is an important factor in the doctor-patient relationship, but mental illness is more difficult to understand than other diseases. Besides traditional skills, virtual reality (VR) has been identified as a promising tool in empathy education. This study aimed to investigate the ability of empathy enhancement, the feasibility of depression education, and the changes in thoughts and attitudes in medical students through a single VR experience. Methods: We recruited medical students and randomly assigned them to two groups based on their completed Interpersonal Response Index scores. Two sets of VR systems were provided; the intervention group experienced the daily life of the depressed medical student, while the control group experienced the general medical student scenario. The improvement of empathy was assessed using the Jefferson Scale of Empathy-Health Professional Students (JSE-HPS), and the change of attitude was assessed through the Implicit Association Test. In addition, other questionnaires were used to evaluate the user experience of this VR system, and correlation analysis was conducted to examine the association between the use of VR and changes in the JSE and IAT scores. Results: A total of 59 medical students were enrolled in this study. The intervention group showed a significant increase in the perspective-taking (pre: mean 5.817, SD 0.536; post: mean 5.947, SD 0.620; P =.03) and compassionate care (pre: mean 5.546, SD 0.581; post: mean 5.721, SD 0.629; P =.01) domains of the JSE score and a significant decrease in the standing in the patient's shoes (SP) domain (pre: mean 3.583, SD 1.253; post: mean 2.967, SD 1.252; P =.002). The Pearson correlation analysis found a significant positive correlation between the JSE score with immersion aspect (r =.308, P =.049) and presence aspect (r =.415, P =.01), and we also found a significant negative correlation between the IAT score and presence aspect (r=-.333, P =.04). Conclusions: This study is the first randomized case-control study to investigate the effect of two different versions of VR on empathy development toward depression for medical students. Although the single VR experience was unable to induce a great improvement in empathy or attitude, the VR system could help medical students enhance their understanding of depressive disorders. Trial registration: This trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (21/03/2024, ACTRN12624000297527). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386683&isReview=true. [ABSTRACT FROM AUTHOR]

Addressing the psychiatric aspects of serious illness in palliative care (PC) is crucial to both care delivery and outcomes. Psychiatric comorbidities are common among patients with PC needs and can significantly impact their total burden of symptomatic distress, overall quality of life, functional independence, and healthcare utilization. Yet, these aspects of care are often deferred to mental health consultant teams in the context of busy PC services and often limited human resources. To provide comprehensive and person-centered care, PC clinicians must understand the interplay between medical conditions and psychiatric presentations within a biopsychosocial framework to respond empathically, efficiently, and effectively. This article is the first of a two-part series developed in collaboration with a group of psychiatric-palliative care specialists. This article explores ten common physical manifestations of psychiatric illness and treatment among patients facing serious illnesses. The second article will provide pragmatic tips PC clinicians should know about the psychiatric manifestations of nonpsychiatric serious illness and treatment. Combined, these two articles support a holistic approach that PC clinicians can use to prioritize and integrate both mental and emotional well-being throughout the continuum of serious illness. [ABSTRACT FROM AUTHOR]

The global prevalence of Major Depressive Disorder (MDD) is increasing at an alarming rate, underscoring the urgent need for timely and accurate diagnoses to facilitate effective interventions and treatments. Electroencephalography remains a widely used neuroimaging technique in psychiatry, due to its non-invasive nature and cost-effectiveness. With the rise of computational psychiatry, the integration of EEG with artificial intelligence has yielded remarkable results in diagnosing depression. This review offers a comparative analysis of two predominant methodologies in research: traditional machine learning and deep learning methods. Furthermore, this review addresses key challenges in current research and suggests potential solutions. These insights aim to enhance diagnostic accuracy for depression and also foster further development in the area of computational psychiatry. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is common in childhood, but its etiopathogenesis is still unclear. Published neurochemical studies mostly focus on monoaminergic system, however, the pathophysiology of MDD cannot be explained by monoamine hypothesis only, medications that have effect on monoamines cannot have effect needed in all patients. We aimed to investigate the poliamine pathway of L-arginine metabolism which is proceeding by way of agmatine in adolescents with MDD. Methods: Our study involved 45 patients with MDD (case group), and 44 healthy controls (control group) between the ages of 13-17. Sociodemographic data form, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version-DSM-5-Turkish, Beck Depression Inventory (BDI), Spielberger's State-Trait Anxiety Inventory were applied to all subjects. All subjects were evaluated in terms of the levels of serum agmatine, putrescine, spermidine, and spermine. Results: The levels of agmatine and spermine were significantly higher and putrescine and spermidine were significantly lower in case group compared with healthy controls. There was significant negative correlation with the levels of putrescine and spermidine between BDI scores, and there was significant positive correlation between the levels of spermine and BDI scores. No correlation found between the levels of agmatine and BDI scores. Conclusion: These differences that the levels of agmatine and polyamines in the MDD group seem to be a field that worth researching. In the future, the evaluation of the arginine/polyamine metabolism in MDD with larger sample and longitudinal studies is going to capable to contribute to a better understanding of the disorder. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a prevalent mental health condition characterized by persistent feelings of sadness and hopelessness, affecting millions globally. The precise molecular mechanisms underlying MDD remain elusive, necessitating comprehensive investigations. Our study integrates transcriptomic analysis, functional assays, and computational modeling to explore the molecular landscape of MDD, focusing on the DLPFC. We identify key genomic alterations and co-expression modules associated with MDD, highlighting potential therapeutic targets. Functional enrichment and protein–protein interaction analyses emphasize the role of astrocytes in MDD progression. Machine learning is employed to develop a predictive model for MDD risk assessment. Single-cell and spatial transcriptomic analyses provide insights into cell type–specific expression patterns, particularly regarding astrocytes. We have identified significant genomic alterations and co-expression modules associated with MDD in the DLPFC. Key genes involved in neuroactive ligand-receptor interaction pathways, notably in astrocytes, have been highlighted. Additionally, we developed a predictive model for MDD risk assessment based on selected key genes. Single-cell and spatial transcriptomic analyses underscored the role of astrocytes in MDD. Virtual screening of compounds targeting GPR37L1, KCNJ10, and PPP1R3C proteins has identified potential therapeutic candidates. In summary, our comprehensive approach enhances the understanding of MDD's molecular underpinnings and offers promising opportunities for advancing therapeutic interventions, ultimately aiming to alleviate the burden of this debilitating mental health condition. Key messages: Our investigation furnishes insightful revelations concerning the dysregulation of astrocyte-associated processes in MDD. We have pinpointed specific genes, namely KCNJ10, PPP1R3C, and GPR37L1, as potential candidates warranting further exploration and therapeutic intervention. We incorporate a virtual screening of small molecule compounds targeting KCNJ10, PPP1R3C, and GPR37L1, presenting a promising trajectory for drug discovery in MDD. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE). Method: In a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall's W test. Results: A significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p < 0.001) as well as in HAM-A scores, from severe to moderate-severe anxiety through the four visits (p < 0.001). Furthermore, only one case was reported as a serious side effect. Nausea and insomnia were the most predominant side effects reported among the studied population. Conclusion: Vortioxetine was found effective and safe among patients with MDD and comorbid GAD. [ABSTRACT FROM AUTHOR]

Background: Evidence from various cohort studies indicate a potential association between depressive disorder and benign prostatic hyperplasia (BPH), yet findings are inconsistent. This study employs bidirectional two‐sample Mendelian randomisation (MR) analysis to explore the causal relationship between BPH and major depressive disorder (MDD). Methods: Genetic variants strongly associated with MDD were extracted as instrumental variables conducted by the Psychiatric Genomics Consortium (PGC). Two sets of genetic variants associated with BPH were extracted from the recent FinnGen and Medical Research Council‐Integrative Epidemiology Unit Consortium of BPH as the discovery and replication stages, respectively. Bidirectional MR analysis employed methods such as inverse variance weighted, MR‐Egger, weighted median, maximum likelihood, and weighted mode. The inverse variance weighted method was primarily used to evaluate the causal relationship. Results: MR analysis in both the discovery and replication stages showed a significant causal relationship between MDD and the risk of BPH (discovery stages, odds ratio (OR) = 1.1146, 95% CI 1.0058–1.2353, P = 0.03852; replication stage, OR: 1.0042, 95% CI 1.0019–1.0065, P = 0.0004). No causal relationship was found between BPH and MDD risk in the reverse MR analysis. Conclusions: Our findings highlight a significant association between MDD and an increased risk of BPH development. Further investigation is needed to elucidate the underlying mechanisms linking depression and BPH. [ABSTRACT FROM AUTHOR]

Aim: Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD). Methods: Liquid chromatography–tandem mass spectrometry (LC–MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme‐linked immunosorbent assay. Results: The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum. Conclusions: The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant depression (TRD) is a severe public health problem and a condition uncommonly addressed by psychological therapies. This paper presents a theoretical model, grounded in established learning principles and in the perspective of behavioral activation (BA), to explain its constitution and development. Method: A review of theoretical models and empirical research on TRD was conducted in major databases. Results: The model reflects how patients with TRD are more susceptible to becoming trapped in their condition by seeking to avoid discomfort through avoidance and escape behaviors, which increasingly drives them away from sources of positive reinforcement. Based on this model, a BA-based intervention protocol is suggested for the treatment of TRD. Through six phases (in a total of thirteen sessions), the protocol guides the intervention towards the reestablishment of personalized routines to increase the probability of reinforcement and reduce avoidance behaviors. Conclusions: Although the model holds significant potential to become an effective intervention in TRD, future research will allow the evaluation of the efficacy of the protocol as a standalone intervention. [ABSTRACT FROM AUTHOR]