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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: Mindfulness‐based cognitive therapy (MBCT) is effective in reducing depressive symptoms in patients with major depressive disorder (MDD). Understanding for whom and how MBCT works may allow for improvements in treatment allocation and effectiveness. In this study, our aim was to investigate depressive rumination, content‐independent perseverative thinking, mindfulness skills, and self‐compassion as potential moderators and mediators of MBCT. Methods: In this non‐randomized controlled trial, patients with persistent (n = 53) or recurrent MDD with (n = 31) or without (n = 51) a current depressive episode were assigned to an intervention (MBCT plus treatment as usual [TAU], n = 94) or control group (TAU only, n = 40) based on the time between the date of inclusion and the start of MBCT. Assessments were carried out before, halfway, and after 8 weeks of MBCT + TAU or TAU. Latent growth models were employed to examine moderation, while cross‐lagged structural equation models were used to assess the mediating effects of several possible mediators of MBCT‐induced change in depressive symptoms and overall functional impairment. Results: MBCT + TAU was more effective in reducing depressive symptoms (and overall functional impairment than TAU with a medium [d = −0.54] and small [d = 0.44] effect size, respectively). Higher baseline levels of rumination and perseverative thinking and lower levels of self‐compassion moderated the effect of MBCT on depressive symptoms and overall functional impairment. Task‐based negative intrusive thoughts moderated the effects of MBCT on overall functional impairment. No mediators were established, particularly due to a lack of effect of MBCT on all assessed mediators at mid‐treatment. For interpretative purposes, a sample split (based on Johnson–Newman values) showed moderate‐to‐large effects in depressive symptom reduction for those with high rumination, high perseverative thinking, and low self‐compassion, while negative‐to‐small nonsignificant effects were found for the opposite traits. Conclusion: In the future, MBCT allocation based on levels of rumination and self‐compassion might lead to a more efficient reduction in depressive symptoms. Directions for mediation analysis within the context of MBCT for depression are discussed. Preregistration: This study was initially preregistered in the Dutch National Trial Register (NL7842). However, due to the NTR no longer being available since June 2022, the trial was reregistered at ClinicalTrials.gov (NCT05802966, dd 09‐Apr‐2023). The statistical analysis plan was adjusted after the start of the trial but before the finalization of data collection (NCT05802966; ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Introduction: Despite the high hopes for the use of transcranial magnetic stimulation (TMS) in the treatment of depression, between 30% and 60.5% of patients do not respond to stimulation. The factors contributing to non-response, especially those related to personality, remain insufficiently investigated. The main aim of our study was to compare the efficacy of active TMS and sham–placebo protocols in combined therapy of treatment-resistant depression with evaluation of possible personality disorders comorbidity. Methods: The study was conducted between December 2019 and December 2022, as a randomized, double-blind, active comparator-controlled and sham-controlled parallel trial. Patients (n = 41) were randomized into one of two experimental conditions (active TMS vs. placebo) and screened before and after stimulation as well as at a 3-month follow-up. Personality disorders were assessed with The Structured Clinical Interview for DSM-5 Personality Disorders. Results: There were no significant differences between the TMS active and sham groups in terms of general characteristics, coexisting personality disorders, and Montgomery–Åsberg Depression Rating Scale scores before stimulation, at the end of stimulation, and after 3 months of stimulation. However, linear regression analysis revealed significant negative associations between the coexistence of personality disorders and the reduction of depressive symptoms from baseline to the end of stimulation. The post-hoc exploratory analysis on the first phase of the RCT confirmed the presence of personality disorders to be a consistent negative influence on the reduction of depressive symptoms post-stimulation, regardless of protocol and experimental condition and demonstrated a smaller percentage reduction in depressive symptoms after stimulation in patients with personality disorders. Discussion: A central conclusion, based on our study, is that transcranial magnetic stimulation for treatment-resistant depression cannot be considered as a method independent of co-occurring personality disorders. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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: 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]

Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (ORcIVW 0.90 per SD increase; 95% CI 0.85–0.95; p = 0.0003); erythrocyte copper (ORcIVW 0.97; 95% CI 0.95–0.99; p = 0.0004); and 25(OH) vitamin D (ORcIVW 0.81; 0.66–0.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (ORcIVW 1.03; 95% CI 1.02–1.05; p = 0.0003) and rMDD (ORcIVW 1.08; 95% CI 1.00–1.08; p = 0.06), and serum magnesium on rMDD (ORcIVW 1.21; 1.01–1.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess. [ABSTRACT FROM AUTHOR]

Introduction: Female infertility is a global issue that impacts on public health seriously and many mental disorders are observed in infertility groups. Methods: To investigate the casual relationship between those, genome-wide association studies summary data of anxiety disorder (n=9,897), broad depression (n=322,580), major depressive disorder (n=480,359 and n=500,199), bipolar disorder (n=51,710), insomnia (n= 462,341), and female infertility (n=126,342) were extracted from the existing datasets and was analyzed through the two-sample mendelian randomization study. The following heterogeneity and sensitivity test were applied to ensure the robustness of results. Results: Based on inverse variance weighted results, major depressive disorder was associated with female infertility (P = 0.0001, odds ratio 1.396, 95 % confidence interval 1.175-1.658). No causal relationship was identified between the other four mental disorders and infertility. was found. Additionally, reverse mendelian randomization did not indicate a causal relationship among these disorders. Discussion: The early identification and management of anxiety symptoms in women of reproductive age, in conjunction with the effective treatment of major depressive disorder, may be crucial for preserving female fertility. [ABSTRACT FROM AUTHOR]

Introduction: Recent resting-state electroencephalogram (EEG) studies have consistently reported an association between aberrant functional brain networks (FBNs) and treatment-resistant traits in patients with major depressive disorder (MDD). However, little is known about the changes in FBNs in response to external stimuli in these patients. This study investigates whether changes in the salience network (SN) could predict responsiveness to pharmacological treatment in resting-state and external stimuli conditions. Methods: Thirty-one drug-naïve patients with MDD (aged 46.61 ± 10.05, female 28) and twenty-one healthy controls (aged 43.86 ± 14.14, female 19) participated in the study. After 8 weeks of pharmacological treatment, the patients were divided into non-remitted MDD (nrMDD, n = 14) and remitted-MDD (rMDD, n = 17) groups. EEG data under three conditions (resting-state, standard, and deviant) were analyzed. The SN was constructed with three cortical regions as nodes and weighted phase-lag index as edges, across alpha, low-beta, high-beta, and gamma bands. A repeated measures analysis of the variance model was used to examine the group-by-condition interaction. Machine learning-based classification analyses were also conducted between the nrMDD and rMDD groups. Results: A notable group-by-condition interaction was observed in the highbeta band between nrMDD and rMDD. Specifically, patients with nrMDD exhibited hypoconnectivity between the dorsal anterior cingulate cortex and right insula (p = 0.030). The classification analysis yielded a maximum classification accuracy of 80.65%. Conclusion: Our study suggests that abnormal condition-dependent changes in the SN could serve as potential predictors of pharmacological treatment efficacy in patients with MDD. [ABSTRACT FROM AUTHOR]

The microcircuitry within superficial layers of the dorsolateral prefrontal cortex (DLPFC), composed of excitatory pyramidal neurons and inhibitory GABAergic interneurons, has been suggested as the neural substrate of working memory performance. In schizophrenia, working memory impairments are thought to result from alterations of microcircuitry within the DLPFC. GABAergic interneurons, in particular, are crucially involved in synchronizing neural activity at gamma frequency, the power of which increases with working memory load. Alterations of GABAergic interneurons, particularly parvalbumin (PV) and somatostatin (SST) subtypes, are frequently observed in schizophrenia. Abnormalities of GABAergic neurotransmission, such as deficiencies in the 67 kDA isoform of GABA synthesis enzyme (GAD67), vesicular GABA transporter (vGAT), and GABA reuptake transporter 1 (GAT1) in presynaptic boutons, as well as postsynaptic alterations in GABAA receptor subunits further contribute to impaired inhibition. This review explores GABAergic abnormalities of the postmortem DLPFC in schizophrenia, with a focus on the roles of interneuron subtypes involved in cognition, and GABAergic neurotransmission within presynaptic boutons and postsynaptic alterations. Where available, comparisons between schizophrenia and affective disorders that share cognitive pathology such as bipolar disorder and major depressive disorder will be made. Challenges in directly measuring GABA levels are addressed, emphasizing the need for innovative techniques. Understanding GABAergic abnormalities and their implications for neural circuit dysfunction in schizophrenia is crucial for developing targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated that breakfast skipping and gut microbiome dysbiosis are associated with a higher risk of major depressive disorder (MDD). However, it remains unknown whether the alteration of gut microbes is implicated in the associations between breakfast skipping and MDD. Methods: Leveraging genome-wide association studies (GWAS) on breakfast skipping, gut microbes, and MDD, we conducted a two-step Mendelian randomization (MR) study to determine the causal associations between breakfast skipping (N = 193,860) and MDD (N = 1,815,091), and evaluate the role of gut microbes (N = 18,340). Genetic variants with a P-value less than 5E-08 were selected as instrumental variables (IVs). The false discovery rate (FDR) method was employed to correct the P-values for multiple tests in gut microbes. Results: Breakfast skipping was associated with an increased risk of MDD (odds ratio [OR] = 1.36, 95%CI = 1.12–1.65, P = 0.002), but no effect of MDD on breakfast skipping was observed (β per doubling odds of MDD =-0.001, 95%CI=-0.024 to 0.023, P = 0.957). After adjusting for multiple comparisons, the MR analysis provided little evidence for an association between breakfast skipping and the abundance of any gut microbes (PFDR>0.05). Among the 21 gut microbes with IVs available, only the abundance of Class Actinobacteria was causally associated with a reduced risk of MDD (OR = 0.85, 95%CI = 0.75–0.97, PFDR=0.015). Conclusions: Our findings demonstrated that breakfast skipping was associated with an increased risk of MDD, but provided little evidence supporting the role of the abundance of gut microbes in it. Further efforts with a large sample size are warranted to clarify the findings. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local‐to‐global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local‐to‐local BA4 – MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local‐to‐global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD. [ABSTRACT FROM AUTHOR]

Background: The study aimed to explore the influence of gender on the prevalence of various somatic symptoms and their associations with suicidal ideation (SI) among patients with major depressive disorder (MDD). Methods: We recruited 3,275 patients with MDD from the National Survey on Symptomatology of Depression (NSSD), among whom 1,745 patients had SI. The clinical characteristics and the prevalence of somatic symptoms across 20 dimensions in MDD patients with SI were compared between male and female patients. Spearman correlation analysis and logistic regression analysis were used to explore the relationship between somatic symptoms and SI. Results: In patients with SI, 32.2% of female participants attributed the onset of MDD to physical concerns, whereas 27% of male patients held a similar perspective (P = 0.032). Female patients exhibited a higher prevalence of early insomnia (64.6% vs. 70.2%) and a lower prevalence of hypersomnia (17.2% vs. 12.9%) and urinary system symptoms (25.0% vs. 17.8%). Logistic regression analysis indicated that female patients displayed a broader range of somatic symptoms identified as risk factors for SI, including increased appetite, respiratory symptoms, circulatory system symptoms, limb pain, and various others. Conclusion: This study unveils gender-specific patterns in somatic symptoms among MDD patients with SI, highlighting the clinical significance of these symptoms in diagnosis and intervention. Understanding how physical concerns contribute to MDD, especially among females, underscores the need for tailored clinical approaches. Recognizing and addressing these symptoms could guide more effective suicide prevention strategies and enhance MDD management in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the levels of oxidant and antioxidant markers in patients with obsessive-compulsive disorder (OCD) and to investigate whether these levels change in the presence of major depressive disorder (MDD) comorbidity. Methods: This study was completed with 23 OCD patients with MDD comorbidity (OCD+MDD), 21 OCD patients without MDD comorbidity (OCD- MDD) and 21 healthy controls. Oxidative stress levels of the cases’ were determined by ischemia modified albumin (IMA) and malondialdehyde (MDA) measurements and antioxidant levels were determined by superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) measurements. One- way analysis of variance (ANOVA) and unpaired Student’s t-test were used to compare the study groups. Post hoc Bonferroni test was used for the degree of significance between groups, and repeated measures analysis of covariance (ANCOVA) was used to investigate the effect of age and gender. Results: IMA and MDA levels were significantly higher in the OCD group compared to the control group, and SOD, CAT and GSH-Px levels were lower in the OCD group compared to the control group (p<0.01). IMA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group, while SOD, CAT and GSH-Px levels were significantly lower in the OCD+MDD group compared to the OCD-MDD group (p<0101). MDA levels were significantly higher in the OCD+MDD group compared to the OCD-MDD group (p=0.009). When the entire OCD patient group was examined, significant, powerful, positive correlations were observed between Y-BOCS and HDRS scores and IMA and MDA, and significant powerful negative correlations between Y-BOCS and HDRS scores and SOD, CAT, and GSH-Px (p<0.001 for all). In OCD+MDD group, oxidative stress markers increased significantly in parallel with the severity of depression, while antioxidant levels decreased (p=0.003 for IMA, p<0.001 for others). Conclusions: We believe that parameters indicating impaired oxidant/antioxidant balance in patients with obsessive-compulsive disorder may help to elucidate the cause of the disease and may be potentially useful biomarkers in the diagnosis and determination of the severity of comorbid MDD. [ABSTRACT FROM AUTHOR]

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions. [ABSTRACT FROM AUTHOR]

Background: The subgenual Anterior Cingulate Cortex (sgACC), as a part of the Anterior Cingulate Cortex and the limbic system plays a crucial role in mood regulation. Previous structural and functional brain imaging studies of the sgACC have revealed alterations of Gray Matter (GM) volumes and Blood Oxygenation Level Dependent signals (BOLD) in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD), suggesting potential biomarker traits for affective disorders. Method: In this study we investigated the gray matter volume of the sgACC in 3 different patient groups: 40 MDD patients, of which 20 were medicated (MDDm) and 20 were unmedicated (MDDu), and 21 medicated BD patients, and compared them with 23 healthy volunteers. We examined GM volume alteration using highresolution 7T Magnetic Resonance Imaging (MRI) which produced quantitative maps of the spin-lattice relaxation time (T1). T1 maps provide high contrast between gray and white matter, and at 7 Tesla voxels with submillimeter resolution can be acquired in a reasonable scan time. We developed a semiautomatic segmentation protocol based on refined landmarks derived from previous volumetric studies using quantitative T1 maps as raw input data for automatic tissue segmentation of GM, WM and CSF (cerebrospinal fluid) tissue. The sgACC ROI was then superimposed on these tissue probability maps and traced manually by two independent raters (F.B., M.M.) following our semiautomatic segmentation protocol. Interrater reliability was calculated on a subset of 10 brain scans for each hemisphere, showing an Intra-Class Correlation coefficient (ICC) r = 0.96 for left sgACC and r = 0.84 for right sgACC respectively. In summary, we have developed a reproducible and reliable semi-automatic segmentation protocol to measure gray matter volume in the sgACC. Based on previous findings from meta-analyses on morphometric studies of the sgACC, we hypothesized that patients with MDD would have lower gray matter sgACC volumes compared to healthy subjects. Results: Post-hoc analysis revealed smaller subgenual volumes for the left hemisphere in both the medicated (MDDm) and non-medicated (MDDu) group versus healthy controls (p = .001, p = .008) respectively. For the right hemisphere, the (MDDu) and BD group exhibited significantly lower subgenual volumes than healthy controls (p < .001, p = .004) respectively. Conclusion: To our knowledge, this is the first morphometric MRI study using T1 maps obtained in high-resolution 7 Tesla MRI to compare MDD and BD patients with healthy controls. [ABSTRACT FROM AUTHOR]

Background: The presence of a mental illness is a known risk factor for suicide mortality and other suicide-related behaviours, including suicidal ideation. We examined prevalence of mental illnesses among adults with and without suicidal ideation in Canada during the pandemic. Data and methods: We used pooled data from the 2020, 2021, & 2023 Survey on COVID-19 and Mental Health to estimate the prevalence of moderate to severe symptoms of generalized anxiety disorder, major depressive disorder, and posttraumatic stress disorder among adults who reported suicidal ideation, compared to those who did not report suicidal ideation. We also conducted the analyses across sociodemographic factors and COVID-19 pandemic-related experiences. Results: Among adults in Canada who reported suicidal ideation, 83.0% also screened positive for at least one of the three mental illnesses. The prevalence of mental illnesses did not differ significantly across sociodemographic factors or pandemic-related experiences. In contrast, the prevalence of at least one mental illness among adults without suicidal ideation was much lower (21.2%), and this prevalence differed by sociodemographic factors and pandemic-related experiences. Interpretation: During the COVID-19 pandemic, most adults in Canada with suicidal ideation had moderate to severe symptoms of mental illness. [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

Background: Emerging studies reveal a shared pathophysiological underpinning for metabolic problems and mental illnesses. The present study aimed to determine the association between atherogenic index of plasma (AIP) and the incidence of major depressive disorder (MDD). Methods: 7,951 subjects of US adults were collected from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. MDD was evaluated through the Patient Health Questionnaire (PHQ-9). Multivariate logistic regression, sensitivity analysis, and spline smoothing plot method were used to identify the relationship between AIP and MDD. The cut-off point was calculated using recursive partitioning analysis when segmenting effects emerged. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were conducted to evaluate the performance of AIP in identifying MDD. Subgroup analyses and interaction tests were used to explore whether the association was stable in different populations. Results: A positive correlation between AIP and PHQ-9 score and MDD was both observed in 7,951 subjects included in the study, with a significant threshold of -0.42 determined using recursive partitioning analysis. In the fully adjusted model, a positive association between AIP and PHQ-9 score and MDD was observed (b=0.46, 95% CI 0.14~0.78; OR=1.42, 95% CI 1.04~1.93). Individuals in the highest AIP quartile had a 0.39-unit higher PHQ-9 score (b=0.39, 95% CI 0.12~0.66) and a significantly 33% greater risk of MDD than those in the lowest AIP quartile (OR=1.33, 95% CI 1.02~1.73). Spline smoothing plot analysis further confirmed the positive and non-linear association between AIP and PHQ-9 and MDD. ROC analysis (AUC=0.771) and the Hosmer-Lemeshow test (c2 = 14.239, P=0.076) suggested an excellent performance and goodness-of-fit of the relatively optimal model. DCA and CIC analysis also revealed a favorable overall net benefit and clinical impact of the model. Subgroup analyses and interaction tests revealed that the association between AIP and PHQ-9 score and MDD remained consistent across different subgroups and was not modified by other covariates, and this positive correlation was more pronounced in those with diabetes or hypertension. Results: A positive correlation between AIP and PHQ-9 score and MDD was both observed in 7,951 subjects included in the study, with a significant threshold of -0.42 determined using recursive partitioning analysis. In the fully adjusted model, a positive association between AIP and PHQ-9 score and MDD was observed (b=0.46, 95% CI 0.14~0.78; OR=1.42, 95% CI 1.04~1.93). Individuals in the highest AIP quartile had a 0.39-unit higher PHQ-9 score (b=0.39, 95% CI 0.12~0.66) and a significantly 33% greater risk of MDD than those in the lowest AIP quartile (OR=1.33, 95% CI 1.02~1.73). Spline smoothing plot analysis further confirmed the positive and non-linear association between AIP and PHQ-9 and MDD. ROC analysis (AUC=0.771) and the Hosmer-Lemeshow test (c2 = 14.239, P=0.076) suggested an excellent performance and goodness-of-fit of the relatively optimal model. DCA and CIC analysis also revealed a favorable overall net benefit and clinical impact of the model. Subgroup analyses and interaction tests revealed that the association between AIP and PHQ-9 score and MDD remained consistent across different subgroups and was not modified by other covariates, and this positive correlation was more pronounced in those with diabetes or hypertension. [ABSTRACT FROM AUTHOR]

In patients with major depressive disorder, various functional areas are impaired, negatively impacting the quality of life. Remission can restore pre-depression functions; however, some patients may still have residual impairments. Distinguishing between near-normal recovery and residual impairment helps identify those at a high risk of relapse risk and helps tailor treatment. Accordingly, we aimed to discover and validate biomarkers that distinguish between near-normal recovery and residual impairment in remission states through serum proteome analysis. Pooled serum and individual serum samples from three groups (depression status, remission status with residual impairment, and remission status with normal recovery) were analyzed using liquid chromatography-tandem mass spectrometry. The combination of four proteins—antithrombin-III, serum amyloid A4 protein, C1q subcomponent subunit B, and serum amyloid P-component—was selected as a candidate biomarker. The trend of protein changes suggests complement C1q subcomponent subunit B and serum amyloid P-component as potential biomarkers for distinguishing remission from residual impairment. Changes in complement C1q subcomponent subunit B and serum amyloid P-component suggest that the complement system and inflammation-related immune mechanisms are associated with residual impairment in remittent major depressive disorder. [ABSTRACT FROM AUTHOR]

Background/Objectives: Empowerment in medicine and psychiatry involves patients gaining control over health-related decisions, improving treatment adherence, outcomes, and satisfaction. This concept is especially significant in psychiatric care due to the complex challenges of mental health conditions, including stigma and impairment of emotional and cognitive functioning. We aim to investigate the correlations between patient trust, decision-making involvement, symptom severity, and perceived empowerment among individuals with Major Depression. Methods: Patients with Major Depressive Disorder were recruited in the "Policlinico G. Rodolico" psychiatry outpatient clinic from November 2022 to June 2023. Inclusion criteria: ages 18–65, ability to consent, stable condition, psychiatric medication history, and recent consultation. Exclusion criteria: psychotic features, bipolar disorder, substance abuse, high suicide risk, and severe comorbidities. Measures included the User Scale for Measuring Empowerment in Mental Health Services (SESM), Trust in Oncologist Scale (TiOS), Clinical Decision-Making Style for Patients (CDMS-P), and Hamilton Depression Rating Scale (HAM-D). Analysis used Kendall's Tau correlation and Two-One-Sided Tests procedure. Results: Seventy-three patients completed the study. No relationship was found between decision-making involvement and perceived empowerment (τ = −0.0625; p = 0.448), or between trust in psychiatrists and empowerment (τ = 0.0747; p = 0.364). An inverse correlation existed between patient involvement in therapy management and trust (τ = −0.2505; p = 0.002). Depression severity inversely correlated with empowerment (τ = −0.2762; p = <.001), but not with trust or decision-making involvement. Conclusions: The lack of significant correlations suggests that decision-making involvement and trust alone may not suffice to enhance empowerment. Trust may encourage patient passivity, while skepticism might drive active involvement. Higher empowerment is associated with less depressive symptoms, highlighting its potential connection with patient outcomes. [ABSTRACT FROM AUTHOR]

Compromised mitochondrial electron transport chain (ETC) activities are associated with depression in humans and rodents. However, the effects of the enhancement of mitochondrial ETC activities on depression remain elusive. We recently reported that an extremely low-frequency electromagnetic field (ELF-EMF) of as low as 10 μT induced hormetic activation of mitochondrial ETC complexes in human/mouse cultured cells and mouse livers. Chronic social defeat stress (CSDS) for 10 consecutive days caused behavioral defects mimicking depression in mice, and using an ELF-EMF for two to six weeks ameliorated them. CSDS variably decreased the mitochondrial ETC proteins in the prefrontal cortex (PFC) in 10 days, which were increased by an ELF-EMF in six weeks. CSDS had no effect on the mitochondrial oxygen consumption rate in the PFC in 10 days, but using an ELF-EMF for six weeks enhanced it. CSDS inactivated SOD2 by enhancing its acetylation and increased lipid peroxidation in the PFC. In contrast, the ELF-EMF activated the Sirt3-FoxO3a-SOD2 pathway and suppressed lipid peroxidation. Furthermore, CSDS increased markers for mitophagy, which was suppressed by the ELF-EMF in six weeks. The ELF-EMF exerted beneficial hormetic effects on mitochondrial energy production, mitochondrial antioxidation, and mitochondrial dynamics in a mouse model of depression. We envisage that an ELF-EMF is a promising therapeutic option for depression. [ABSTRACT FROM AUTHOR]

Objectives: Melancholic depression (MD) is a common subtype of major depressive disorder (MDD). It is difficult to treat because its neurobiological basis is poorly understood. Therefore, to investigate whether MD patients have any structural changes in gray matter (GM) and the molecular foundation of these changes, we combined voxel‐based morphometry (VBM) analysis with neurotransmitter system‐derived mapping from public data. Methods: 137 drug‐naive MDD patients and 75 healthy controls (HCs) were recruited for structural magnetic resonance imaging. The imaging results were analyzed using VBM analysis. MDD patients were then divided into MD and nonmelancholic depression (NMD) subgroups according to their scores on the Montgomery–Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale. Next, we analyzed the spatial correlation between the changes in the gray matter volume (GMV) maps and the neurotransmitter receptor/transporter protein density maps provided by the JuSpace toolbox. Results: Compared to HCs, patients with MD had significant GMV reduction in the bilateral hippocampus, bilateral thalamus, right amygdala, and right posterior cingulate cortex (PCC)/precuneus. Compared to patients with NMD, MD patients had significant GMV reduction in the bilateral PCC/precuneus and lateral occipital cortex. Moreover, compared to HCs, changes in GMV introduced by MD were spatially associated with the serotonin transporter, cannabinoid receptor, and μ‐opioid receptor. Compared to NMD patients, changes in GMV introduced by MD were spatially associated with the vesicular acetylcholine transporter. Conclusion: The present study discovered abnormal GMV alterations in patients with subtypes of depression. We also found a series of neurotransmitter receptors that may be associated with the alterations. The findings of the current study may provide a more comprehensive understanding of the molecular mechanisms underlying the structural abnormalities in subtypes of depression and potentially offer new insights into developing new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Depression and anxiety are major public health issues; however, there is an unmet need for novel, effective, and accessible treatments, particularly in rural communities. Blueberries are an unexplored nutraceutical for these conditions due to their excellent nutritional profile, with particularly high levels of polyphenols and anthocyanins and benefits on mood, cognition, and health. Here, we present a narrative review of the literature concerning the etiology and treatments of major depressive disorder (MDD) and generalized anxiety disorder (GAD). In both animal and human studies, blueberry supplementation can ameliorate behavioral symptoms of both anxiety and depression. The mechanistic underpinnings of these behavioral improvements are not fully defined, but likely involve biochemical alterations in the gut–brain axis, including to inflammatory cytokines, reactive oxygen species, and growth factors. We also review the limitations of traditional therapies in rural settings. Finally, we assess the potential benefit of nutraceutical interventions, particularly blueberries, as novel therapeutics for these distinct, yet related mental health issues. [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 multicenter 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]

Background: Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Hypericumperforatum (HP) is a traditional herb that has been shown to have antidepressant effects, but its mechanism is unclear. This study aims to identify the molecular targets of HP for the treatment of MDD. Methods: We performed differential analysis and weighted gene co-expression network analysis (WGCNA) with blood mRNA expression cohort of MDD and healthy control to identify DEGs and significant module genes (gene list 1). Three databases, CTD, DisGeNET, and GeneCards, were used to retrieve MDD-related gene intersections to obtain MDD-predicted targets (gene list 2). The validated targets were retrieved from the TCMSP database (gene list 3). Based on these three gene lists, 13 key pathways were identified. The PPI network was constructed by extracting the intersection of genes and HP-validated targets on all key pathways. Key therapeutic targets were obtained using MCODE and machine learning (LASSO, SVM-RFE). Clinical diagnostic assessments (Nomogram, Correlation, Intergroup expression), and gene set enrichment analysis (GSEA) were performed for the key targets. In addition, immune cell analysis was performed on the blood mRNA expression cohort of MDD to explore the association between the key targets and immune cells. Finally, molecular docking prediction was performed for the targets of HP active ingredients on MDD. Results: Differential expression analysis and WGCNA module analysis yielded 933 potential targets for MDD. Three disease databases were intersected with 982 MDD-predicted targets. The TCMSP retrieved 275 valid targets for HP. Separate enrichment analysis intersected 13 key pathways. Five key targets (AKT1, MAPK1, MYC, EGF, HSP90AA1) were finally screened based on all enriched genes and HP valid targets. Combined with the signaling pathway and immune cell analysis suggested the effect of peripheral immunity on MDD and the important role of neutrophils in immune inflammation. Finally, the binding of HP active ingredients (quercetin, kaempferol, and luteolin) and all 5 key targets were predicted based on molecular docking. Conclusions: The active constituents of Hypericumperforatum can act on MDD and key targets and pathways of this action were identified. [ABSTRACT FROM AUTHOR]

Background: Depression is a leading cause of disability worldwide, and treatments could be more effective. Identifying methods to improve treatment success has the potential to reduce disease burden dramatically. Preparing or "priming" someone to respond more effectively to psychotherapy (e.g., cognitive behavioral therapy [CBT]) by preceding sessions with aerobic exercise, a powerful neurobiological activator, could enhance the success of the subsequently performed therapy. However, the success of this priming approach for increasing engagement of working mechanisms of psychotherapy (e.g., increased working alliance and behavioral activation) has yet to be formally tested. Methods: The CBT + trial will be a parallel-arm randomized controlled trial that will recruit 40 adult participants with DSM-5 diagnosed depression (verified with clinical interview) via referrals, mass emails, local flyers, and social media posts. Participants will be randomized to an ActiveCBT or CalmCBT condition. The ActiveCBT group will receive an 8-week CBT intervention primed with 30 min of moderate-intensity aerobic exercise (cycling on a stationary bike at a 13 rating of perceived exertion). The CalmCBT group will receive the same 8-week CBT intervention while resting for 30 min before CBT (i.e., cycling vs no cycling is the only difference). The primary outcome measures will be mean working alliance (assessed with the client version of the Working Alliance Inventory—Short Revised) and mean behavioral activation (self-reported Behavioral Activation for Depression Scale) recorded at each of the 8 therapy sessions. Secondary outcomes include evaluation of state anhedonia and serum brain-derived neurotrophic factor before the active/calm conditions, between the condition and therapy, and after the therapy. Additional exploratory analyses will evaluate group differences in algorithm-generated ratings of therapist-participant interactions via the Lyssn platform. Discussion: The novel approach of priming CBT with moderate-intensity aerobic exercise evaluated in a randomized controlled trial (CBT + trial) has the potential to demonstrate the usefulness of exercise as an augmentation strategy that improves working mechanisms of therapy and overall treatment outcomes for adults with depression. Trial registration: ClinicalTrials.gov NCT06001346. Registered on August 21, 2023. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is associated with deficits in cognitive function, thought to be related to underlying decreased hedonic experiences. Further research is needed to fully elucidate the role of functional brain activity in this relationship. In this study, we investigated the neurofunctional correlate of the interplay between cognitive function and hedonic experiences in medication-free MDD using functional near-infrared spectroscopy (fNIRS). Methods: We examine differences of brain activation corresponding to the verbal fluency test (VFT) between MDD patients and healthy controls (HCs). Fifty-six MDD patients and 35 HCs underwent fMRI scanning while performing the VFT. In exploratory analyses, cognitive performance, as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), four dimensions of hedonic processing (desire, motivation, effort, and consummatory pleasure) measured by the Dimensional Anhedonia Rating Scale (DARS), and relative changes in oxygenated hemoglobin concentration during the VFT were compared across groups. Results: Patients with MDD demonstrated impairments in sustained attention and working memory, accompanied by lower total and subscale scores on the DARS. Compared to healthy controls, MDD patients exhibited reduced activation in the prefrontal cortex (PFC) during the VFT task (t = 2.32 to 4.77, p < 0.001 to 0.02, FDR corrected). DARS motivation, desire, and total scores as well as sustained attention, were positively correlated with activation in the dorsolateral PFC and Broca's area (p < 0.05, FDR corrected). Conclusions: These findings indicate that changes in prefrontal lobe oxygenated hemoglobin levels, a region implicated in hedonic motivation and cognitive function, may serve as potential biomarkers for interventions targeting individuals with MDD. Our results corroborate the clinical consensus that the prefrontal cortex is a primary target for non-invasive neuromodulatory treatments for depression. [ABSTRACT FROM AUTHOR]