Major Depressive Disorder Research Articles

Genetic polymorphism involved in major depressive disorder: a systemic review and meta-analysis

Background and objectiveGenetic 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 methodsPubMed 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.ResultsThe 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.ConclusionAt 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.

Bipolar Disorder and Suicide

Suicide is a dramatic and frequent consequence of bipolar disorder. Prevention of suicidal behavior involves an assessment of suicidal vulnerability factors (history of suicidal behavior, impulsive personality, etc.), characteristics of depression (agitated depression, a subtype of bipolar disorder, etc.), psychiatric comorbidities, and stress factors. Psychosocial at the same time with the characteristics of suicidal behavior in a depressed subject (severe or repeated gestures in particular) make it possible to direct the diagnosis towards a bipolar disorder rather than a major depressive disorder. In addition to training caregivers to screen for bipolar disorder and assess suicidal behavior, the withdrawal of lethal means, networking, and treatment of depression reduce the risk of suicidal behavior. At the medicinal level, the use of lithium salts could be of particular interest in subjects at high risk of suicide.

The Preventive Role of Perceived Social Support in Postpartum Psychiatric Morbidity: Insights from a Rural Tertiary Care Teaching Hospital in South India

Abstract Introduction: Postpartum psychiatric disorders show a rising trend in developing countries, where the lack of social support is a major risk factor. Evidence from Western scientific literature also reports of similar preventive role of social support in postpartum psychiatric states. However, the attitudes toward childbearing may differ across cultures and also within the same cultural sphere. With this background, we aimed to assess the perceived social support and its association with postpartum psychiatric morbidity in a rural setting in South India. Methodology: A total of 100 postpartum women who met the inclusion and exclusion criteria were included in the study following their consent. Sociodemographic data sheet and Edinburgh Postnatal Depression Scale, Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Text Revision (DSM IV-TR), and Multidimensional Scale of Perceived Social Support were administered on them. Appropriate statistical analysis was done. P <0.05 was considered statistically significant. Results: The majority of our sample recorded high perceived social support (76%), with 90% reporting high support from a special person. 10% had major depressive disorder, out of which 6% recorded melancholia, and 7% recorded suicidality on DSM IV-TR. Increasing age had lower perceived social support, P = 0.024. As perceived social support was reduced, increased psychiatric morbidity was significantly noted, with suicidality and melancholia. Conclusions: Our study finds a significant association between perceived social support and postpartum depression (PPD). Lesser social support was associated with increased suicidality and melancholia features in cases of PPD. Amplification of social support in expectant mothers is a useful way to safeguard against postpartum psychiatric disorders.

Invisible Victims and the Case for OTC SSRIs.

Major depressive disorder is one of the most common serious illnesses worldwide; the disease is also among those with the lowest rates of treatment. Barriers to access to care, both practical and psychological, contribute significantly to these low treatment rates. Among such barriers are regulations in many nations that require a physician's prescription for most pharmacological treatments including selective serotonin reuptake inhibitors (SSRIs). These rules are designed to protect patients. However, such regulations involve a tradeoff between the welfare of "visible" victims, who might suffer negative consequences from a lack of regulation, and the well-being of invisible "victims," who likely experience negative consequences that result from increased barriers to care. This article explores these tradeoffs and argues in favor of shifting SSRIs from prescription-only to over-the-counter status.

Deep phenotyping reveals CRH and FKBP51-dependent behavioral profiles following chronic social stress exposure in male mice.

The co-chaperone FKBP51, encoded by FKBP5 gene, is recognized as a psychiatric risk factor for anxiety and depressive disorders due to its crucial role in the stress response. Another key modulator in stress response regulation is the corticotropin releasing hormone (CRH), which is co-expressed with FKBP51 in many stress-relevant brain-regions and cell-types. Together, they intricately influence the balance of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary stress response systems. Previous research underscores the potential moderating effects these genes have on the regulation of the stressful life events towards the vulnerability of major depressive disorder (MDD). However, the specific function of FKBP51 in CRH-expressing neurons remains largely unexplored. Here, through deep behavioral phenotyping, we reveal heightened stress effects in mice lacking FKBP51 in CRH co-expressing neurons (CRHFKBP5-/-), particularly evident in social contexts. Our findings highlight the importance of considering cell-type specificity and context in comprehending stress responses and advocate for the utilization of machine-learning-driven phenotyping of mouse models. By elucidating these intricacies, we lay down the groundwork for personalized interventions aimed at enhancing stress resilience and individual well-being.

A Study on Serum Cortisol Levels and Thyroid Profile in Patients With Unipolar Depression

A Study on Serum Cortisol Levels and Thyroid Profile in Patients With Unipolar Depression

LATE ONSET PSYCHOSIS IN THE ELDERLY

Late-onset psychosis in the elderly is a condition characterized by the onset of psychotic symptoms, such as hallucinations and delusions, after the age of 60. Although psychosis at younger ages is often associated with primary psychiatric disorders such as schizophrenia, diagnosis in the elderly is more complex, as it involves the need to differentiate between various conditions that can affect the brain and behavior, such as dementias, neurological disorders and factors related to brain aging. The impact of brain aging, such as diminished cognitive abilities and changes in brain structure, also plays an important role in the development and course of psychosis in this age group. The aim of this work is to analyze the differential diagnosis of late onset psychosis in the elderly, exploring the conditions that can mimic psychotic symptoms and the impact of brain aging on this process. It also aims to assess the implications of this diagnosis for clinical management and patients’ quality of life. This study uses a systematic review to investigate late onset psychosis in the elderly, its relationship with neurodegenerative diseases, differential diagnoses with dementias and therapeutic approaches, both pharmacological and non-pharmacological. The search was carried out in databases such as SciELO, PubMed, LILACS and Journal of Neurosciences, and included analysis of critical reviews, empirical studies and clinical guidelines. Additional data was obtained from population studies and clinical analyses involving geriatric patients with psychosis. The differential diagnosis of late onset psychosis is challenging, as it involves distinguishing between primary and secondary psychiatric causes. Neurodegenerative disorders, such as Alzheimer’s disease and dementia with Lewy bodies, are often associated with psychotic symptoms in the elderly. Likewise, disorders such as major depression with psychotic features and delirium can present with similar symptoms, and a detailed clinical assessment is essential. The exclusion of underlying medical factors, such as infections, metabolic disorders and adverse effects of medication, is crucial to ensure an accurate diagnosis. Brain aging, in turn, plays a key role in the vulnerability of the elderly to psychosis. With age, structural and functional changes occur in the brain, such as cortical atrophy, reduced neuronal density and alterations in dopaminergic pathways, which can predispose to the emergence of psychotic symptoms. These changes make the brain more susceptible to stress factors, inflammation and sensory deficits, which can precipitate psychotic episodes. Thus, the treatment of late onset psychosis involves a careful approach, given the sensitivity of the elderly to antipsychotics and the increased risk of side effects. The choice of treatment must balance efficacy in controlling symptoms with minimizing risks, and the use of low doses and constant monitoring are recommended to avoid complications. It is therefore concluded that late onset psychosis in the elderly presents significant diagnostic challenges, requiring a multifactorial approach that takes into account brain aging and the various medical conditions that can mimic or contribute to psychotic symptoms. Differential diagnosis is essential to ensure appropriate treatment, which, when properly targeted, can substantially improve patients’ quality of life. The impact of brain ageing on vulnerability to psychosis highlights the need for detailed clinical assessment and individualized therapeutic strategies for this population group.

Repetitive transcranial magnetic stimulation elicits weight loss and improved insulin sensitivity in type 2 diabetic rats.

Type 2 diabetes (T2D) accounts for the majority of diabetes incidences and remains a widespread global chronic disorder. Apart from early lifestyle changes, intervention options for T2D are mainly pharmaceutical. Repetitive transcranial magnetic stimulation (rTMS) has been approved by the FDA as a therapeutic intervention option for major depressive disorders, with further studies also indicating its role in energy metabolism and appetite. Considering its safe and non-invasive properties, we evaluated the effects of rTMS on systemic metabolism using T2D rats. We observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10-day exposure. Improved systemic insulin sensitivity was maintained after a 21-day treatment period, accompanied by modest yet significant weight loss. Circulating serum lipid levels, including those of cholesteryl ester, tryglyceride and ceramides, were also reduced following rTMS application. RNA-seq analyses further revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism. Altered expression of hypothalamic genes that are related to appetite regulation, neural activity and ether lipid metabolism were also implicated. In summary, our data report a positive impact of rTMS on systemic insulin sensitivity and weight management of T2D rats. The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.

Cost-effectiveness of screening and treating alcohol use and depression among people living with HIV in Zimbabwe: a mathematical modeling study

BackgroundAlcohol use disorder (AUD) and major depressive disorder (MDD) drive HIV transmission in many sub-Saharan African settings. The impact of screening and treating AUD and MDD on HIV outcomes is unknown. We aimed to identify the cost-effectiveness of AUD and MDD interventions in Zimbabwe, and their potential contribution to reaching Zimbabwe’s Ending the HIV Epidemic 2030 goal.MethodsUsing a validated HIV compartmental transmission model in Zimbabwe, we compared four policy scenarios: prevention as usual (baseline); implement AUD screening (using AUDIT) and treatment (motivational interviewing and cognitive-behavioral therapy); implement MDD screening (using PHQ-9) and treatment (cognitive-behavioral therapy); and implement screening and treatment for both. Outcomes were HIV incidence projections, infections averted through 2030, quality-adjusted life-years gained, cost per infection averted, and cost per QALY gained. Analyses considered “spillover,” when treatment for AUD also results in an improvement in MDD and the converse. Sensitivity analyses identified cost reductions necessary for AUD and MDD interventions to be as cost-effective as other HIV interventions, particularly the scale-up of long-acting PrEP.ResultsAUD and MDD combined will be responsible for 21.1% of new HIV infections in Zimbabwe by 2030. Without considering spillover, compared to the baseline, MDD intervention can reduce new infections by 5.4% at $2039/infection averted and $3186/QALY. AUD intervention can reduce new infections by 5.8%, but at $2,968/infection averted and $4753/QALY, compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.1% at $2810/infection averted and $4229/QALY, compared to baseline. Considering spillover, compared to the baseline, MDD intervention can reduce new infections by 6.4% at $1714/infection averted and $2630/QALY. AUD intervention can reduce new infections by 7.4%, but at $2299/infection averted and $3560/QALY compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.9% at $2247/infection averted and $3382/QALY compared to baseline. For MDD intervention to match the cost-effectiveness of scaling long-acting PrEP, the cost of MDD intervention would need to be reduced from $16.64 to $12.88 per person.ConclusionsImplementing AUD and MDD interventions can play an important role in HIV reduction in Zimbabwe, particularly if intervention cost can be decreased while preserving effectiveness.

Use of passively collected actigraphy data to detect individual depressive symptoms in a clinical subpopulation and a general population.

The presentation of major depressive disorder (MDD) can vary widely due to its heterogeneity, including inter- and intraindividual symptom variability, making MDD difficult to diagnose with standard measures in clinical settings. Prior work has demonstrated that passively collected actigraphy can be used to detect MDD at a disorder level; however, given the heterogeneous nature of MDD, comprising multiple distinct symptoms, it is important to measure the degree to which various MDD symptoms may be captured by such passive data. The current study investigated whether individual depressive symptoms could be detected from passively collected actigraphy data in a (a) clinical subpopulation (i.e., moderate depressive symptoms or greater) and (b) general population. Using data from the National Health and Nutrition Examination Survey, a large nationally representative sample (N = 8,378), we employed a convolutional neural network to determine which depressive symptoms in each population could be detected by wrist-worn, minute-level actigraphy data. Findings indicated a small-moderate correspondence between the predictions and observed outcomes for mood, psychomotor, and suicide items (area under the receiver operating characteristic curve [AUCs] = 0.58-0.61); a moderate-large correspondence for anhedonia (AUC = 0.64); and a large correspondence for fatigue (AUC = 0.74) in the clinical subpopulation (n = 766); and a small-moderate correspondence for sleep, appetite, psychomotor, and suicide items (AUCs = 0.56-0.60) in the general population (n = 8,378). Thus, individual depressive symptoms can be detected in individuals who likely meet the criteria for MDD, suggesting that wrist-worn actigraphy may be suitable for passively assessing these symptoms, providing important clinical implications for the diagnosis and treatment of MDD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.07 ± 2.73). A total of 174 participants (120 women, 54 men) were randomized to active (n = 87, mean age = 37.09 ± 11.14 years) or sham (n = 87, mean age = 38.32 ± 10.92 years) treatment. tDCS consisted of five sessions per week for 3 weeks then three sessions per week for 7 weeks in a 10-week trial, followed by a 10-week open-label phase. Each session lasted 30 min; the anode was placed over the left dorsolateral prefrontal cortex and the cathode over the right dorsolateral prefrontal cortex (active tDCS 2 mA and sham tDCS 0 mA, with brief ramp up and down to mimic active stimulation). As the primary outcome, depressive symptoms showed significant improvement when measured using the Hamilton Depression Rating Scale: active 9.41 ± 6.25 point improvement (10-week mean = 9.58 ± 6.02) and sham 7.14 ± 6.10 point improvement (10-week mean = 11.66 ± 5.96) (95% confidence interval = 0.51-4.01, P = 0.012). There were no differences in discontinuation rates. In summary, a 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety. ClinicalTrials.gov registration: NCT05202119.

Exploring Patient Empowerment in Major Depressive Disorder: Correlations of Trust, Active Role in Shared Decision-Making, and Symptomatology in a Sample of Italian Patients.

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.

Effects of Gepirone-ER on Sexual Function in Patients With Major Depressive Disorder.

Effects of Gepirone-ER on Sexual Function in Patients With Major Depressive Disorder.

Perturbation graphs, invariant causal prediction and causal relations in psychology.

Networks (graphs) in psychology are often restricted to settings without interventions. Here we consider a framework borrowed from biology that involves multiple interventions from different contexts (observations and experiments) in a single analysis. The method is called perturbation graphs. In gene regulatory networks, the induced change in one gene is measured on all other genes in the analysis, thereby assessing possible causal relations. This is repeated for each gene in the analysis. A perturbation graph leads to the correct set of causes (not nec-essarily direct causes). Subsequent pruning of paths in the graph (called transitive reduction) should reveal direct causes. We show that transitive reduction will not in general lead to the correct underlying graph. We also show that invariant causal prediction is a generalisation of the perturbation graph method and does reveal direct causes, thereby replacing transitive re-duction. We conclude that perturbation graphs provide a promising new tool for experimental designs in psychology, and combined with invariant causal prediction make it possible to re-veal direct causes instead of causal paths. As an illustration we apply these ideas to a data set about attitudes on meat consumption and to a time series of a patient diagnosed with major depression disorder.

The effect of prebiotic supplementation on serum levels of tryptophan and kynurenine in obese women with major depressive disorder: a double-blinded placebo-controlled randomized clinical trial

ObjectiveThe objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD).ResultsIn this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30–40 kg/m2) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either “Prebiotic group” (received 10 g/day inulin) or “Placebo group” (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks.Trial registration: The trial was registered in the Iranian registry of clinical trials at 2018-08-02 (https://www.irct.ir/; registration number: IRCT20100209003320N15).

Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations.

Ketamine has a long and very eventful pharmacological history. Its enantiomer, esketamine ((S)-ketamine), was approved by the US Food and Drug Administration (FDA) and EMA for patients with treatment-resistant depression (TRD) in 2019. The number of approved indications for ketamine and esketamine continues to increase, as well as the number of clinical trials. This analysis provides a quantitative overview of the use of ketamine and its enantiomers in clinical trials during 2014-2024. A total of 363 trials were manually assessed from clinicaltrial.gov with the search term "Ketamine." The highest number of trials were found for the FDA-approved indications: anesthesia (~22%) and pain management (~28%) for ketamine and TRD for esketamine (~29%). Clinical trials on TRD for both ketamine and esketamine also comprised a large proportion of these trials, and interestingly, have reached phase III and phase IV status. Combinatorial treatment of psychiatric disorders and non-psychiatric conditions with pharmacological and non-pharmacological combinations (electroconvulsive therapy, psychotherapeutic techniques, virtual reality, and transcranial magnetic stimulation) is prevalent. Sub-anesthetic doses of ketamine may represent novel therapeutic avenues in neuropsychiatric conditions, that is, major depression, schizophrenia, and bipolar disorder, where glutamate excitotoxicity and oxidative stress are likely to be involved. The study suggests that the number of ketamine studies will continue to grow and possible ketamine variants can be approved for treatment of additional indications.

Effects of open-skill and closed-skill exercise on subthreshold depression in female adolescents: A randomized controlled trial

BackgroundSubthreshold depression (SD) affects a significant proportion of adolescent females, posing a risk of major depression in later life. This study examines the effects of open-skill exercise (OSE) and closed-skill exercise (CSE) on SD, executive function (EF), and emotional states in female adolescents. MethodsA double-blind randomized controlled trial involved 95 female adolescents (mean age = 16.73 ± 0.42 years) with SD symptoms. Participants were assigned to OSE, CSE, or control (CON) groups and underwent an 8-week exercise program. Primary outcomes were assessed using the Beck Depression Inventory (BDI-13) and the Center for Epidemiological Studies Depression Scale (CES-D), with secondary outcomes including EF tasks and emotional assessments. Differences were examined using generalized linear mixed models with intention-to-treat and multiple imputation. ResultsBoth OSE and CSE significantly reduced depressive symptoms, with CSE showing greater improvement. EF assessments showed enhanced cognitive flexibility and working memory in both exercise groups at 4 weeks, and superior inhibitory control and cognitive flexibility in the CSE group at 8 weeks. Emotional assessments indicated a notable reduction in negative emotions in the CSE group after 8 weeks. ConclusionsBoth OSE and CSE reduce SD symptoms in female adolescents, with CSE providing more sustained benefits for EF and emotional states. Further research on exercise interventions for mental health is warranted.Trial registration number: ChiCTR2400081139

Interoception mediates the association between social support and sociability in patients with major depressive disorder.

Interoception dysfunction has an important impact on the onset and development of major depressive disorder (MDD). Social support serves as a protective factor against MDD, and sociability also plays a significant role in this condition. These interconnected constructs-social support and sociability-play pivotal roles in MDD. However, no research on the mechanisms underlying the associations between social support and sociability, particularly the potential role of interoception, have been reported. To investigate the mediating effect of interoception between social support and social ability and to explore the independent role of social support in sociability. The participants included 292 patients with MDD and 257 healthy controls (HCs). The patient health questionnaire 9, the multidimensional assessment of interoception awareness, version 2 (MAIA-2), the social support rating scale (SSRS), and the Texas social behavior inventory (TSBI) were used to assess depression, interoception, social support, and sociability, respectively. A mediation analysis model for the eight dimensions of interoception (noticing, not distracting, not worrying, attention regulation, emotional awareness, self-regulation, body listening, and trust), social support, and sociability were established to evaluate the mediating effects. A partial correlation analysis of eight dimensions of the MAIA-2, SSRS, and TSBI scores, with demographic data as control variables, revealed pairwise correlations between the SSRS score and both the MAIA-2 score and TSBI score. In the major depression (MD) group, the SSRS score had a positive direct effect on the TSBI score, while the scores for body listening, emotional awareness, self-regulation, and trust in the MAIA-2C had indirect effects on the TSBI score. In the HC group, the SSRS score had a positive direct effect on the TSBI score, and the scores for attention regulation, emotional awareness, self-regulation, and trust in the MAIA-2C had indirect effects on the TSBI score. The proportion of mediators in the MD group was lower than that in the HC group. Interoceptive awareness is a mediating factor in the association between social support and sociability in both HCs and depressed patients. Training in interoceptive awareness might not only help improve emotional regulation in depressed patients but also enhance their social skills and support networks.

The Effect of Adding Agomelatine to Escitalopram in the Treatment of Major Depressive Disorder

Major Depressive Disorder (MDD) is a psychiatric illness that imposes a high cost on the patient and the community. Over the past few decades, a variety of treatments have been used to treat depression. One of the most common treatments for depression is medication. Today, specific serotonin reuptake inhibitors are the first line of treatment for major depression. Another drug that has been considered in the treatment of depression is agomelatine.Objective of this study was to evaluate the effect of adding agomelatine to Escitalopram in treatment of major depressive disorder.Materials and methods. This study was a double-blind randomized clinical trial with before and after designs (b and a). In this study, 70 patients with MDD referred to psychiatric clinics affiliated with Yazd University of Medical Sciences were studied. Patients were randomly divided into two groups of 35 patients (agomelatine + Escitalopram and Escitalopram + placebo) and were treated for 12 weeks. Depression Scale was the Hamilton Depression Inventory and was assessed before treatment, 1, 2, and 3 months after treatment. Variables such as gender, age, marital status, level of education, occupation, and duration of illness were also collected. The data were entered into SPSS version 18 software and analyzed using statistical tests.Results. Of the 70 patients studied, 31 (44.3%) were male and 39 (55.7%) were female. There was not significant difference between gender distribution (p=0.810), marital status(p=0.789), job (p=0.651) and educational level (p=0.794). Also, no significant difference was found between the mean variables: age (p=0.563) and duration of depression (p=0.958). There was a statistically significant difference between the mean score of depression 2 months after treatment (p=0.10) and 3 months after treatment (p=0.023) in the two groups. Also the mean depression score after treatment compared to before, was significantly lower in both groups (p=0.000). Also, no significant difference was found between the frequency of drug side effects in the two groups (p=0.970).Conclusion. Adding agomelatine to Escitalopram is more effective than mood-boosting depression as a result of depression or depressive disorder alone.Future researchers in the field of MDD treatment could consider investigating the long-term effects and comparative efficacy of combining agomelatine with other antidepressants beyond Escitalopram to further enhance treatment outcomes for patients with MDD.

Novel therapeutic targets for major depressive disorder related to oxidative stress identified by integrative multi-omics and multi-trait study.

Oxidative stress (OS) is strongly implicated in the pathophysiology of major depressive disorder (MDD) but the molecular mechanisms remain largely unknown. The purpose of this study is to identify genes related to both OS and MDD, and further to evaluate the utility of these genes as diagnostic markers and potential treatment targets. We searched datasets related to MDD from the Gene Expression Omnibus (GEO) database for differentially expressed genes (DEGs) also related to OS according to GeneCards. Bioinformatics analyses and machine learning algorithms were used to identify hub genes mediating OS-MDD interactions. A summary data-based Mendelian randomization (SMR) approach was employed to identify possible causal genes for MDD from blood tissue eQLT data. These investigations identified 32 genes mediating OS-MDD interactions, while SMR analysis identified KCNE1 (OR = 1.057, 95%CI = 1.013-1.102, P value = 0.010), MAPK3 (OR = 1.023, 95%CI = 1.004-1.043, P value = 0.020), and STIP1 (OR = 0.792, 95%CI = 0.641-0.979, P value = 0.031) as OS-related causal genes for MDD. These genes may thus serve as useful diagnostic markers and potential therapeutic targets.