Major Depressive Disorder Group Research Articles

Exploring the role of affective temperaments: predicting major depressive disorder in the context of borderline personality disorder

ABSTRACT Purpose Major depressive disorder (MDD) is a complex condition believed to arise from a multifaceted interplay of genetic, environmental, and biological factors. In the pursuit of understanding its etiology, two elements that warrant investigation are borderline personality disorder (BPD) and affective temperaments. We aim to gain deeper insights into the mechanisms underlying this debilitating mental health condition. Method The dataset comprises individuals who sought assistance from psychiatry outpatient clinics for diverse reasons during the period spanning from 2018 to 2022. These individuals underwent SCID-II assessments to diagnose borderline personality disorder (BPD) and also completed the TEMPS-A temperament tests. Results The mean years of schooling was lower in the MDD group (p = 0.014). Two groups are compared in terms of affective temperament. Depressive (p < 0.0001), cyclothymic (p < 0.0001), anxious (p = 0.001), and irritable (p < 0.0001) temperament scores were statistically higher in the MDD group. Apart from the scale scores, the prevalence of affective temperament was evaluated and the same temperaments (depressive (p < 0.0001), cyclothymic (p < 0.0001), anxious (p = 0.001), and irritable (p < 0.0001)) were found to be significantly higher in the MDD group. Diagnosis of BPD is higher in the MDD group (p = 0.002). Binary logistic regression analysis revealed that the presence of cyclothymic temperament and marital status may be predictor factors for the development of MDD (p < 0.0001, CI: 0.001–0.121 and p = 0.002, CI: 1.550–7.172, respectively). Conclusion Notably, higher scores in cyclothymic temperament and experiencing loneliness have been identified as significantly associated with MDD. Interestingly, in patients with comorbid BPD-MDD, the presence of cyclothymic temperament appears to be a more critical factor than personality traits. This finding underscores the potential role of cyclothymic temperament in contributing to the co-occurrence of BPD and MDD.

Enhanced classification and severity prediction of major depressive disorder using acoustic features and machine learning.

Previous studies have classified major depression and healthy control groups based on vocal acoustic features, but the classification accuracy needs to be improved. Therefore, this study utilized deep learning methods to construct classification and prediction models for major depression and healthy control groups. 120 participants aged 16-25 participated in this study, included 64 MDD group and 56 HC group. We used the Covarep open-source algorithm to extract a total of 1200 high-level statistical functions for each sample. In addition, we used Python for correlation analysis, and neural network to establish the model to distinguish whether participants experienced depression, predict the total depression score, and evaluate the effectiveness of the classification and prediction model. The classification modelling of the major depression and the healthy control groups by relevant and significant vocal acoustic features was 0.90, and the Receiver Operating Characteristic (ROC) curves analysis results showed that the classification accuracy was 84.16%, the sensitivity was 95.38%, and the specificity was 70.9%. The depression prediction model of speech characteristics showed that the predicted score was closely related to the total score of 17 items of the Hamilton Depression Scale(HAMD-17) (r=0.687, P<0.01); and the Mean Absolute Error(MAE) between the model's predicted score and total HAMD-17 score was 4.51. This study's results may have been influenced by anxiety comorbidities. The vocal acoustic features can not only effectively classify the major depression and the healthy control groups, but also accurately predict the severity of depressive symptoms.

Irritability in youth: Trauma, maltreatment, and bullying in mood disorders

ObjectiveDisruptive Mood Dysregulation Disorder (DMDD) is characterized by irritability and anger outbursts, categorized under depressive disorders along with Major Depressive Disorder (MDD) in DSM-5. This study aims to investigate exposure to peer bullying and trauma in irritable youth with DMDD and compare it with those with MDD and healthy controls. MethodsThis cross-sectional study included 313 participants aged 12–17 (DMDD: 103, MDD: 105, healthy controls: 105; mean age 15.0±1.6). The diagnosis was established using the Schizophrenia for School-Aged Children Present and Lifetime Version (K-SADS-PL) semi-structured interview. The Olweus Bullying Questionnaire, Childhood Trauma Questionnaire, and sociodemographic forms were utilized. ResultsBoth DMDD and MDD groups experienced significantly more physical, sexual, and emotional abuse, as well as physical and emotional neglect, compared to the healthy control group. Among the DMDD group, 34.9% were bullies, 42.7% were victims, and 18.4% were bully-victims. ConclusionAdolescents diagnosed with DMDD are at increased risk for experiencing peer bullying and trauma. Emotional dysregulation and intense outbursts of anger predispose these individuals to both perpetrate and fall victim to peer bullying, as well as to become bully-victims. Including irritable adolescents in peer bullying intervention programs may be beneficial. Additionally, considering the elevated risk of anger outbursts and irritability in individuals exposed to trauma, they should be closely monitored.

Correlates of cannabis use and cannabis use disorder among adolescents with major depressive disorder and bipolar disorder in the National Comorbidity Survey-Adolescent Supplement (NCS-A)

BackgroundDespite evidence regarding prevalence and correlates of cannabis use (CU) and cannabis use disorder (CUD) in major depressive disorder (MDD) and bipolar disorder (BD) in adults, little is known about this topic among adolescents. MethodsData is from the 2001–2004 National Comorbidity Survey–Adolescent Supplement, an in-person, cross-sectional epidemiologic survey of mental disorders. Participants included adolescents, ages 13–18 years, with MDD (n = 354 with CU, n = 70 with CUD, n = 688 with no CU), BD (n = 79 with CU, n = 32 with CUD, n = 184 with no CU), or adolescents without mood disorders (n = 1413 with CU, n = 333 with CUD, n = 6970 with no CU). Analyses examined prevalence and correlates of CU and CUD within MDD and BD groups. ResultsCU was most prevalent in adolescents with MDD followed by adolescents with BD then controls. CUD was most prevalent in adolescents with BD followed by adolescents with MDD then controls. In covariate-adjusted ordinal logistic regression models, within MDD and BD, CU and CUD groups had significantly higher odds of lifetime suicidal ideation/attempts, as well as other significant indicators of clinical severity. LimitationsBased on changes in cannabis acceptance, potency, and availability in the two decades since this study was conducted, present findings may underestimate adverse cannabis associations. ConclusionCU and CUD are both associated with adverse clinical characteristics in a community-based sample of adolescents with MDD and BD. Evidence that risks of cannabis use extend across the spectrum of use is important for adolescents with MDD and BD, in whom cannabis-related consequences tend to be more severe.

The Relationship of Immune Markers with Severity and Heritability of Depressive Disorder: A Cross-Sectional Hospital-Based Study from North India

Background: Inflammatory response plays a pivotal role in the pathophysiology of depression. With this background, we planned this study to see if immune markers, interleukin 6 (IL-6), and erythrocyte sedimentation rate (ESR) are raised in subjects with major depressive disorder (MDD) and compare its level with healthy controls and first-degree relatives of subjects. We also explored if variation in the level of these markers was related to the severity of depression. Methods: This comparative observational study included 120 subjects, who were divided into three groups of 40 individuals each. Group 1 was the MDD group, group 2 was the healthy first-degree relative group, and group 3 was the healthy control group. All the subjects were then made to undergo estimation of IL-6 (pg/mL) and ESR (mm/h) from our hospital biochemistry lab. The patients in group 1 were additionally screened for the severity of depression. Results: The mean IL-6 and ESR measure within the MDD group was 9.20 ± 13.40 (pg/mL) and 5.90 ± 5.35 (mm/h), respectively. We found that the mean and median values of both IL-6 and ESR were highest in the MDD group as compared to other groups, which were statistically significant ( p &lt;0.05). A pairwise comparison found no significant difference in the IL-6 and ESR scores among the healthy controls and healthy first-degree relatives. The mean of IL-6 was highest in individuals with moderate severity of depression, while the mean of ESR was highest in individuals with severe depression. Conclusion: The immune markers, IL-6 and ESR, were significantly raised in the MDD group; however, the levels did not correlate significantly with the differential severity of the depressive disorder as per Hamilton depression rating scale (HAM-D) scores.

Frontal Activity of Recent Suicide Attempters: EEG spectrum Power Performing Raven Task.

Background: Deficits in problem-solving may be related to vulnerability to suicidal behavior. We aimed to identify the electroencephalographic (EEG) power spectrum associated with the performance of the Raven as a reasoning/problem-solving task among individuals with recent suicide attempts. Methods: This study with the case-control method, consisted of 61 participants who were assigned to three groups: Suicide attempt + Major Depressive Disorder (SA + MDD), Major Depressive Disorder (MDD), and Healthy Control (HC). All participants underwent clinical evaluations and problem-solving abilities. Subsequently, EEG signals were recorded while performing the Raven task. Results: The SA + MDD and MDD groups were significantly different from the HC group in terms of anxiety, reasons for life, and hopelessness. Regarding brain oscillations in performing the raven task, increased theta, gamma, and betha power extending over the frontal areas, including anterior prefrontal cortex, dlPFC, pre-SMA, inferior frontal cortex, and medial prefrontal cortex, was significant in SA + MDD compared with other groups. The alpha wave was more prominent in the left frontal, particularly in dlPFC in SA + MDD. Compared to the MDD group, the SA + MDD group had a shorter reaction time, while their response accuracy did not differ significantly. Conclusions: Suicidal patients have more frontal activity in planning and executive function than the two other groups. Nevertheless, it seems that reduced activity in the left frontal region, which plays a crucial role in managing emotional distress, can contribute to suicidal tendencies among vulnerable individuals. Limitation The small sample size and chosen difficult trials for the Raven task were the most limitations of the study.

Abnormal activation patterns in MT+ during visual motion perception in major depressive disorder.

Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC). Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC. Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus. Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.

The impact of ACTH levels on neurotransmitters and antioxidants in patients with major depressive disorder: A novel investigation

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

The mediating role of family functioning between childhood trauma and depression severity in major depressive disorder and bipolar disorder

BackgroundChildhood trauma (CT) and family functioning exert significant influences on the course and long-term outcome of major depressive disorder (MDD) and bipolar disorder (BD) patients. Hence, we examined the intricate relationship between CT, family function, and the severity of depressive episodes in MDD and BD patients. Methods562 patients with depressive episodes (336 MDD and 226 BD) and 204 healthy controls (HCs) were included in this retrospective study. The 17-item Hamilton Depression Rating Scale (HAMD-17), Childhood Trauma Questionnaire (CTQ), and Family Adaptability and Cohesion Evaluation Scale (FACES II-CV) were assessed. Pearson correlation analysis and mediation analysis were performed. ResultsCT had both a direct and indirect impact on depression severity in MDD and BD groups. In MDD, family adaptability mediated the impact of all CT subtypes on depression severity (Effect = 0.113, [0.030, 0.208]). In BD, family cohesion played a mediating role between emotional neglect (EN) and HAMD-17 scores (Effect = 0.169, [0.008, 0.344]). Notable differences were observed in onset age, illness duration, episode frequency, family history, and CT subtypes between MDD and BD (P < 0.05). LimitationsThis study has several limitations including recall bias, lack of objective family functioning measures, small sample size, and cross-sectional design. ConclusionsFamily functioning mediated the impact of CT on depressive symptoms severity in MDD and BD patients. MDD patients with a history of CT exhibited reduced family adaptability, while BD patients with a history of EN had weaker familial emotional bonds. Our findings highlighted the importance of family-focused preventive interventions in mitigating the long-term effects of CT.

Mind-wandering in daily life in depressed individuals: An experience sampling study

BackgroundA diagnostic criterion for Major Depressive Disorder (MDD) is difficulty concentrating and increased distractibility. One form of distraction that occurs in everyday life is mind-wandering. The current study aims to test how individuals with MDD and healthy controls differ in their mind-wandering in everyday life. MethodsAdults diagnosed with MDD (n = 53) and healthy controls (n = 53) completed a week of experience sampling, with prompts administered up to eight times per day. At each prompt, participants reported the occurrence and characteristics of their mind-wandering. They also reported levels of momentary negative affect (NA), positive affect (PA), and rumination. ResultsMDD participants reported mind-wandering almost twice as often as healthy control participants. Compared to healthy participants, MDD participants rated their mind-wandering as more negative, but did not differ in terms of temporal orientation. Higher NA and lower PA predicted mind-wandering in the MDD group but not healthy controls, even after controlling for rumination. Time-lagged analyses revealed that current mind-wandering predicted future levels of PA in MDD participants but not in healthy controls; in contrast, current NA and PA did not predict future mind-wandering. LimitationsLimitations include our examination of specific forms of mind-wandering (i.e., we did not sample the full spectrum of this construct). ConclusionsIndividuals with MDD frequently report engaging in mind-wandering in everyday life, and this appears to be coupled with affect. Mind-wandering may have maladaptive effects in MDD and could serve as a target for intervention.

Increased expression of ER stress, inflammasome activation, and mitochondrial biogenesis-related genes in peripheral blood mononuclear cells in major depressive disorder.

A subset of major depressive disorder (MDD) is characterized by immune system dysfunction, but the intracellular origin of these immune changes remains unclear. Here we tested the hypothesis that abnormalities in endoplasmic reticulum (ER) stress, inflammasome activity and mitochondrial biogenesis contribute to the development of systemic inflammation in MDD. RT-qPCR was used to measure mRNA expression of key organellar genes from peripheral blood mononuclear cells (PBMCs) isolated from 186 MDD and 67 healthy control (HC) subjects. The comparative CT (2-ΔΔCT) method was applied to quantify mRNA expression using GAPDH as the reference gene. After controlling for age, sex, BMI, and medication status using linear regression models, expression of the inflammasome (NLRC4 and NLRP3) and the ER stress (XBP1u, XBP1s, and ATF4) genes was found to be significantly increased in the MDD versus the HC group. Sensitivity analyses excluding covariates yielded similar results. After excluding outliers, expression of the inflammasome genes was no longer statistically significant but expression of the ER stress genes (XBP1u, XBP1s, and ATF4) remained significant and the mitochondrial biogenesis gene, MFN2, was significantly increased in the MDD group. NLRC4 and MFN2 were positively correlated with serum C-reactive protein concentrations, while ASC trended significant. The altered expression of inflammasome activation, ER stress, and mitochondrial biogenesis pathway components suggest that dysfunction of these organelles may play a role in the pathogenesis of MDD.

A Comparison of Cognitive Disengagement Syndrome in Children with Major Depression Versus Attention Deficit and Hyperactivity Disorder

Objective: There is growing evidence that Cognitive Disengagement Syndrome (CDS) is a distinct construct, supported by both empirical research and clinical differentiation. CDS demonstrates a stronger association with the inattentive type of Attention Deficit Hyperactivity Disorder (ADHD-IA), compared to its correlation with hyperactivity/impulsivity symptoms. Several studies have identified a significant positive relationship between CDS and internalizing symptoms such as anxiety and depression. To our knowledge, no study has explored CDS in children with major depression (MD). In the present study, we compared children with MD but without ADHD to children with ADHD but without depression in terms of CDS. We examined whether children with MD would have greater CDS when compared to children with ADHD. Methods: Thirty-six adolescents with ADHD, and twenty-five adolescents with MD, aged 12 to 18 years old, were administered the Barkley Child Attention Scale (BCAS), Turgay's DSM-IV Based ADHD and Disruptive Behavior Disorders Screening Scale, and the Children’s Depression Rating Scale-Revised (CDRS-R). Results: The majority of the ADHD and MD groups were boys. The MD group had significantly higher BCAS scores than the ADHD group (U=287.0, p=0.016). In the ADHD group, the severity of BCAS scores was inversely correlated with ADHD-Hyperactivity/impulsivity scores (r=-0.681, p&lt;0.001). In the MD group, there was a significant positive relationship between BCAS and CDRS scores (r= 0.493, p=0.012). Conclusions: The findings of this study highlight the transdiagnostic relevance of CDS by demonstrating its association with depression, independent of ADHD. This underscores the importance of considering CDS in the assessment and treatment of depression across various clinical contexts.

Regional brain structural network topology mediates the associations between white matter damage and disease severity in first-episode, Treatment-naïve pubertal children with major depressive disorder

Puberty is a vulnerable period for the onset of major depressive disorder (MDD) due to considerable neurodevelopmental changes. Prior diffusion tensor imaging (DTI) studies in depressed youth have had heterogeneous participants, making assessment of early pathology challenging due to illness chronicity and medication confounds. This study leveraged whole-brain DTI and graph theory approaches to probe white matter (WM) abnormalities and disturbances in structural network topology related to first-episode, treatment-naïve pediatric MDD. Participants included 36 first-episode, unmedicated adolescents with MDD (mean age 15.8 years) and 29 age- and sex-matched healthy controls (mean age 15.2 years). Compared to controls, the MDD group showed reduced fractional anisotropy in the internal and external capsules, unveiling novel regions of WM disruption in early-onset depression. The right thalamus and superior temporal gyrus were identified as network hubs where betweenness centrality changes mediated links between WM anomalies and depression severity. A diagnostic model incorporating demographics, DTI, and network metrics achieved an AUROC of 0.88 and a F1 score of 0.80 using a neural network algorithm. By examining first-episode, treatment-naïve patients, this work identified novel WM abnormalities and a potential causal pathway linking WM damage to symptom severity via regional structural network alterations in brain hubs.

Maternal emotion regulation abilities affect adolescent depressive symptoms by mediating their emotion regulation ability: An ERP study

Adolescents with major depressive disorder (MDD) experience significant difficulties in emotion regulation. This study aimed to explore emotion regulation in adolescents with depression using an emotion regulation paradigm combined with event-related potentials (ERP) while investigating the relationship between maternal emotion regulation and adolescent depressive symptoms through a mediation model. Overall, 38 healthy controls (HC) and 57 adolescents with depression (MDD) rated the pictures they saw according to aversive reappraisal (reappraisal of an aversive picture or down-regulate aversive emotions), aversive watch, and neutral conditions. Adolescents with depression gave more negative ratings to aversive images, and the emotional regulation success index (ERSI) of adolescents with depression was lower than that of healthy individuals. ERP data revealed an elevation in late positive potential (LPP) amplitude during the aversive reappraisal and aversive watch conditions compared with that in the neutral condition in the MDD group. Compared with the HC group, adolescents with depression showed larger LPP amplitudes under aversive watch conditions. The aversive reappraisal condition evoked a larger LPP than that in the other conditions in the HC group in the late time windows. The ΔLPP (separating the variability in the ERP wave associated with emotion regulation) was larger in the HC group than in the MDD group. Mediation analysis revealed that maternal emotion regulation influenced adolescent depression levels through its effect on the adolescent’s emotion regulation. These findings provide important insights into the emotion regulation process in adolescents with depression and offer suggestions for clinical interventions.

Quantification of Glutathione and Its Associated Spontaneous Neuronal Activity in Major Depressive Disorder and Obsessive-Compulsive Disorder

BackgroundGlutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy using the Mescher-Garwood point-resolved spectroscopy sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders. MethodsBy combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging, we quantified brain GSH and glutamate in the medial prefrontal cortex and precuneus and explored relationships between GSH levels and intrinsic neuronal activity as well as clinical symptoms among healthy control (HC) participants (n = 30), people with major depressive disorder (MDD) (n = 28), and people with obsessive-compulsive disorder (OCD) (n = 28). ResultsGSH concentrations were lower in the medial prefrontal cortex and precuneus in both the MDD and OCD groups than in the HC group. In the HC group, positive correlations were noted between GSH and glutamate levels and between GSH and fractional amplitude of low-frequency fluctuations in both regions. However, while these correlations were absent in both patient groups, there was a weak positive correlation between glutamate and fractional amplitude of low-frequency fluctuations. Moreover, GSH levels were negatively correlated with depressive and compulsive symptoms in MDD and OCD, respectively. ConclusionsThese findings suggest that reduced GSH levels and an imbalance between GSH and glutamate could increase oxidative stress and alter neurotransmitter signaling, thereby leading to disruptions in GSH-related neurochemical-neuronal coupling and psychopathologies across MDD and OCD. Understanding these mechanisms could provide valuable insights into the processes that underlie these disorders and potentially become a springboard for future directions and advancing our knowledge of their neurobiological foundations.

Serum Thiols and Ischemia-Modified Albumin Levels in Children With Major Depressive Disorder: A Cross-Sectional Study.

Introduction This cross-sectional study aimed to investigate potential biomarkers of oxidative stress by analyzing serum thiol-disulfide homeostasis (TDH) and ischemia-modified albumin (IMA) levels in children who have been diagnosed with major depressive disorder (MDD). Methods The study included 24 medication-naive children aged seven to 17 years diagnosed with MDD and 19 healthy controls matched for age, gender, and body mass index. Clinical interviews were conducted using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL-DSM-5), and diagnoses were made according to DSM-5. The Child Depression Inventory (CDI) and the Clinical Global Impression Scale-Severity (CGI-S) were also administered to the participants. Venous blood samples were taken from all subjects to assess TDH and IMA levels, considered potential oxidative stress indicators. Results The study showed no significant difference in TDH and IMA levels between the MDD and the control groups. Although not statistically significant, it was observed that native thiol and total thiol levels were higher in the MDD group. No direct relationship was found between disease severity and either TDH or IMA levels. Conclusion In conclusion, while there were no significant differences in the levels of TDH and IMA, higher levels of both native and total thiols were found in the MDD group.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center

BackgroundDepression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD.MethodsWe conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data.ResultsThe initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD.ConclusionsOur analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Brain-derived neurotrophic factor and C-reactive protein (CRP) biomarkers in suicide attempter and non-attempter major depression disorder (MDD) patients

BackgroundIn the available literature, levels of BDNF and CRP have been reported to correlate with suicide in depressive patients but there are inconsistencies in the results. We aimed to evaluate and compare BDNF and CRP concentrations in MDD patients with(MDD + SA) and without suicide attempts (MDD-SA) and healthy controls.Methods30 (MDD + SA) patients, 30 (MDD-SA) patients, and 26 healthy controls were enrolled in the study. Age, sex, and BMI of patients were recorded. Blood sample was obtained for measurement of BDNF and CRP. Smoking and drug history, family history of suicide, and history of self-harm were also documented. Data were analyzed with SPSS version 22 and R version 4.1.1.Results86 patients in three groups were evaluated (mean age: 28.45 ± 9.27 years, 56.71% female). Baseline and demographic parameters except for self-harm (40%, 3.3%, and 0% for MDD + SA, MDD-SA, and healthy controls, respectively, p = 0.001) did not differ between groups. CRP level was not significantly different between groups. BDNF showed a significant difference between groups (17.35, 16.45, and 19.43 for three groups, respectively, p < 0.001). An increase in BDNF decreased the odds of both depression and suicide. Roc curve showed excellent power for BDNF in discriminating MDD groups With healthy group.Roc can notdicrimiate MDD + SA and MDD-SA.ConclusionIn our study, the concentration of BDNF differed significantly between depressed patients with/without suicide attempts and healthy controls which shows the association of BDNF with depression development and not suicide attempts. We could not find any association between CRP level and suicide attempt but still larger cohorts are needed for a definite conclusion.

Association between major depressive disorder and gut microbiota dysbiosis.

Major depressive disorder (MDD) affects 300 million people globally. Because dysbiosis may alter the central nervous system, it plays a potential role in this disorder. Dysbiosis is characterized by a decrease in microbial diversity and an increase in proinflammatory species. The human gut microbiota refers to the trillions of microbes, such as bacteria, that live in the human gut. The purpose of this study was to compare the gut microbiota of patients with MDD with that of healthy controls. This case-control study involved 35 MDD cases and 35 healthy age- and sex-matched controls. Stool samples were collected and subjected to quantitative real-time PCR. Four intestinal bacterial phyla (firmicutes, bacteroidetes, actinobacteria, and proteobacteria) were investigated by 16SrRNA analysis. The findings indicated a relative abundance of bacteroidetes to firmicutes in the control and case groups was 0.66 vs. 1.33, respectively (p < .05). There were no significant differences in actinobacteria or proteobacteria among those in the MDD group compared to the healthy control group. Gut microbiota dysbiosis may contribute to the onset of depression, underscoring the importance of understanding the relationship between MDD and gut microbiota. Firmicutes, which produce short-chain fatty acids, are crucial for intestinal health. However, dysbiosis can disrupt the gut microbiota, impacting the central nervous system and contributing to the onset of depression.

Neurocognitive and clinical profile of male patients with substance use disorder in early remission phase with and without comorbid depression

Substance Use Disorder (SUD) represents one of the most frequent conditions worldwide which commonly coexists with major depressive disorder (MDD). This comorbidity (SUD + MDD) is one of the most prevalent with patients showing certain social and clinical characteristics that could lead to a worsening of their cognitive performance. However, despite these particularities, only a few studies have addressed the possible differences in cognitive performance between patients with SUD + MDD compared with those with SUD-only patients. Therefore, the aim of this study is to examine the clinical and cognitive profile of patients with SUD + MDD vs. SUD-only who are in early remission phase. For this purpose, 271 male patients underwent a clinical and neuropsychological assessment (SUD + MDD group: N = 101; SUD-only group: N = 170). Results indicated that SUD + MDD patients showed worse cognitive performance than SUD in visuospatial reasoning, verbal memory and learning, recognition, and processing speed even after a 3-month period of abstinence. Furthermore, these patients exhibited more self-reported prefrontal symptoms, as well as worse social and clinical conditions. This study indicates that the neurocognitive and clinical profile of patients with SUD + MDD could represent a risk since their characteristics have been associated with poorer recovery and prognosis. Our results could be helpful in clinical practice highlighting the need for cognitive remediation strategies in these populations, providing information that would allow the implementation of more appropriate treatments and preventive strategies.