Severity Of Major Depressive Disorder Research Articles

Contribution of physiological dynamics in predicting major depressive disorder severity

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

Altered resting-state brain activity of the superior parietal cortex and striatum in major depressive disorder and schizophrenia

BackgroundResting-state functional magnetic resonance imaging (fMRI) studies have shown altered brain activity in major depressive disorder (MDD) and schizophrenia (SZ). Despite differing diagnoses, SZ and MDD share similar features. However, functional brain activity similarities and differences between SZ and MDD remain unclear. MethodsParticipants with MDD, SZ, and normal controls (n=36 each) underwent resting-state fMRI scans. Amplitude of low-frequency fluctuations (ALFF) was used to analyze the preprocessed rs-fMRI data. One-way ANOVAs and post hoc analyses compared ALFF values in different brain regions. Pearson correlation analysis examined associations with clinical symptoms. ResultsComparison among the three groups revealed significant differences in ALFF values within the left superior parietal cortex (L-SPC) and bilateral striatum. Through pairwise comparisons, patients with SZ but not patients with MDD were found to exhibit increased striatum ALFF values relative to NC individuals, but decreased in MDD. Meanwhile, L-SPC ALFF values were significantly increased in patients with SZ relative to both normal control individuals and patients with MDD, while no differences in these values were observed between the normal control and MDD groups. The Pearson correlation analyses showed significant positive correlations between ALFF in the striatum and PANSS positive score, but no significant correlation with other symptom severity in SZ and MDD. ConclusionThese findings support the hypothesis of alterations in brain functional activity as a fundamental component of the pathogenesis of MDD and SZ. The observed differences in functional brain activity in the superior parietal cortex and striatum between MDD and SZ provide a neuroimaging basis that can contribute to the differential diagnosis of these debilitating conditions.

The effect of major depressive disorder comorbidity on ischemia-modified albumin levels, a marker of oxidative stress, and antioxidant defense system in patients with obsessive compulsive disorder.

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. 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. 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). 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.

The Relationship Between Brain-Derived Neurotrophic Factor and Serotonin in Major Depressive and Bipolar Disorders: A Cross-Sectional Analysis.

Background Mood disorders like major depressive disorder (MDD) and bipolar disorder (BD) involve complex interactions between brain-derived neurotrophic factor (BDNF) and serotonin. While extensive research has explored these factors individually, their combined effects and interactions in these disorders are less understood. This study uniquely addresses this gap by examining how BDNF and serotonin interact and relate to mood disorder severity, providing new insights into their joint role in MDD and BD. Objectives The objective of this study was to examine the correlation between serum BDNF and plasma serotonin levels and to assess how these correlations relate to the severity of symptoms and overall disease severity in MDD and BD. Methodology This cross-sectional study, conducted at the Khyber Medical University, Peshawar, from January to September 2023, examined the correlation between BDNF and serotonin in individuals with MDD and BD. Participants (n = 63) aged 18-65 were recruited based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, excluding those with neurological disorders, substance abuse, or severe medical illness. A control group of 21 healthy individuals was matched by age and gender. Data collection involved demographic details, clinical history, and comorbid diagnoses assessed using the Mini International Neuropsychiatric Interview (MINI). Mood disorder severity was measured using the Hamilton Depression Rating Scale (HAM-D) for MDD and the Young Mania Rating Scale (YMRS) for BD, along with additional assessments (Beck Depression Inventory, Global Assessment of Functioning). Serum BDNF and serotonin levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Statistical analyses included t-tests, Mann-Whitney U tests, Pearson correlations, and subgroup analyses to assess relationships between biomarkers, mood disorder severity, and influencing factors. Results BDNF levels were found to be 20.1 ± 5.3 ng/mL in MDD, 18.5 ± 4.7 ng/mL in BD, and 25.9 ± 6.2 ng/mL in controls. Serotonin levels were 45.8 ± 12.6 ng/mL in MDD, 43.2 ± 11.4 ng/mL in BD, and 52.1 ± 14.3 ng/mL in controls. In the MDD group, significant negative correlations were observed between BDNF levels and mood disorder severity (r = -0.32, p = 0.045), whereas serotonin levels did not show significant correlations (r = -0.21, p = 0.23). In the BD group, BDNF levels also showed a significant negative correlation with manic symptoms (r = -0.28, p = 0.048), but serotonin levels showed no significant correlation. Subgroup analyses revealed that participants under 40 years had higher BDNF levels (22.8 ± 5.6 ng/mL) compared to those aged 40 and above (19.7 ± 4.3 ng/mL). Females showed higher BDNF levels (24.5 ± 6.3 ng/mL) than males (19.3 ± 3.8 ng/mL). Participants not on medication had higher BDNF levels (23.6 ± 5.1 ng/mL) compared to those on medication (17.9 ± 4.2 ng/mL). Those without comorbidities also had higher BDNF levels (23.8 ± 5.9 ng/mL) than those with comorbidities (18.2 ± 4.5 ng/mL), while serotonin levels varied similarly across these subgroups. Conclusion Lower BDNF levels are associated with mood disorders and symptom severity, indicating their potential as a biomarker.

PRKCB methylation: a potential biomarker of MDD with childhood chronic stress, a cross-sectional study in drug-naive, first-episode adolescent MDD

ABSTRACT The purpose of this study was to investigate the relationship between childhood chronic stress(CCS), Protein kinase C beta (PRKCB) methylation and adolescent major depressive disorder (MDD). After recruiting 100 adolescents with MDD and 50 healthy controls (HCs), we evaluated the severity of CCS. PRKCB methylation was assessed by pyrosequencing using whole blood-derived DNA. To explore the relationship between CCS, PRKCB and adolescent MDD, we conducted correlation analysis and regression analysis, and constructed multiplicative interaction models and generalized linear models. PRKCB methylation and CCS were both found to be associated with MDD, and CCS was associated with PRKCB methylation. No significant CCS-PRKCB methylation interactions were observed. However, we found the interaction of CCS and MDD on PRKCB methylation. Our results found that PRKCB methylation was influenced by CCS and the disease itself, and PRKCB methylation was significantly positively associated with MDD severity, suggesting that PRKCB methylation may be a potential biomarker for adolescent MDD. This study is a cross-sectional observational study, which cannot draw the conclusion of causality. Prospective cohort studies are needed to further examine the relationship between CCS, adolescent MDD, and PRKCB methylation.

Impact of air pollution exposure on the severity of major depressive disorder: Results from the DeprAir study.

Major depressive disorder (MDD) is one of the most prevalent medical conditions worldwide. Different factors were found to play a role in its etiology, including environmental ones (e.g., air pollution). The aim of this study was to evaluate the association between air pollution exposure and MDD severity. Four hundred sixteen MDD subjects were recruited. Severity of MDD and functioning were evaluated through five rating scales: Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Sheehan Disability Scale (SDS). Daily mean estimates of particulate matter with diameter ≤10 (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO2), and apparent temperature (AT) were estimated based on subjects' residential addresses. Daily estimates of the 2 weeks preceding recruitment were averaged to obtain cumulative exposure. Multivariate linear and ordinal regression models were applied to assess the associations between air pollutants and MDD severity, overall and stratifying by hypersusceptibility and AT. Two-thirds of subjects were women and one-third had a family history of depression. Most women had depression with symptoms of anxiety, while men had predominantly melancholic depression. NO2 exposure was associated with worsening of MDD severity (HAMD: β = 1.94, 95% confidence interval [CI], [0.41-3.47]; GAF: β = -1.93, 95% CI [-3.89 to 0.02]), especially when temperatures were low or among hypersusceptible subjects. PM exposure showed an association with MDD severity only in these subgroups. Exposure to air pollution worsens MDD severity, with hypersusceptibility and lower temperatures being exacerbating factors.

Exploring the use of immunomethylomics in the characterization of depressed patients: A proof-of-concept study

Alterations in DNA methylation and inflammation could represent valid biomarkers for the stratification of patients with major depressive disorder (MDD). This study explored the use of DNA-methylation based immunological cell-type profiles in the context of MDD and symptom severity over time.In 119 individuals with MDD, DNA-methylation was assessed on whole blood using the Illumina Infinium MethylationEPIC 850 k BeadChip. Quality control and data processing, as well as cell type estimation was conducted using the RnBeads package. The cell type composition was estimated using epigenome-wide DNA methylation signatures, applying the Houseman method, considering six cell types (neutrophils, natural killer cells (NK), B cells, CD4+ T cells, CD8+ T cells and monocytes). Two cytokines (IL-6 and IL-1β) and hsCRP were quantified in serum. We performed a hierarchical cluster analysis on the six estimated cell-types and tested the differences between these clusters in relation to the two cytokines and hsCRP, depression severity at baseline, and after 6 weeks of treatment (celecoxib/placebo + vortioxetine). We performed a second cluster analysis with cell-types and cytokines combined. ANCOVA was used to test for differences across clusters. We applied the Bonferroni correction.After quality control, we included 113 participants. Two clusters were identified, cluster 1 was high in CD4+ cells and NK, cluster 2 was high in CD8+ T-cells and B-cells, with similar fractions of neutrophils and monocytes. The clusters were not associated with either of the two cytokines and hsCRP, or depression severity at baseline, but cluster 1 showed higher depression severity after 6 weeks, corrected for baseline (p = 0.0060). The second cluster analysis found similar results: cluster 1 was low in CD8+ T-cells, B-cells, and IL-1β. Cluster 2 was low in CD4+ cells and natural killer cells. Neutrophils, monocytes, IL-6 and hsCRP were not different between the clusters. Participants in cluster 1 showed higher depression severity at baseline than cluster 2 (p = 0.034), but no difference in depression severity after 6 weeks.DNA-methylation based cell-type profiles may be valuable in the immunological characterization and stratification of patients with MDD. Future models should consider the inclusion of more cell-types and cytokines for better a prediction of treatment outcomes.

The Effects of Variation in the GABAA Receptor Gene on Anxious Depression are Mediated by the Functional Connectivity Between the Amygdala and Middle Frontal Gyrus.

γ-aminobutyric acid (GABA) and its main receptor, the GABAA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC. The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62healthy controls (HC).All participants underwent genotyping for polymorphisms of GABAA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABAA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABAA receptor gene MGPS and AD clinical features. Compared with the NAD group, the AD group had a higher GABAA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD. The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.

C-reactive protein in anhedonia among patients with major depressive disorder and its relation to suicidal ideation

BackgroundThere is evidence that major depressive disorder (MDD) with its cardinal symptoms, anhedonia and suicide, are linked with raised inflammatory markers like C-reactive protein (CRP). This case–control study investigated the correlation between high sensitive CRP (Hs-CRP), anhedonia, suicidal ideation, and depression severity in MDD patients.MethodsForty-one MDD patients and 47 healthy controls were recruited. MDD diagnosis was confirmed using DSM-5 criteria. Depression severity, anhedonia, and suicidal ideation were assessed using standardized scales. Serum Hs-CRP levels were measured as an inflammatory marker.ResultsMDD cases had significantly greater Hs-CRP levels compared to controls. Additionally, Hs-CRP levels were positively correlated with both anhedonia and suicidal ideation in MDD cases. Depression severity was significantly linked with both anhedonia and suicidal ideation.ConclusionThis study suggests a link between inflammation, anhedonia, suicidal ideation, and depression severity in MDD patients. Additional research is necessary to find out the principal mechanisms.

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.

Glycolytic metabolism: Food for immune cells, fuel for depression?

Inflammation is one biological pathway thought to impact the brain to contribute to major depressive disorder (MDD) and is reliably associated with resistance to standard antidepressant treatments. While peripheral immune cells, particularly monocytes, have been associated with aspects of increased inflammation in MDD and symptom severity, significant gaps in knowledge exist regarding the mechanisms by which these cells are activated to contribute to behavioral symptoms in MDD. One concept that has gained recent appreciation is that metabolic rewiring to glycolysis in activated myeloid cells plays a crucial role in facilitating these cells’ pro-inflammatory functions, which may underlie myeloid contribution to systemic inflammation and its effects on the brain. Given emerging evidence from translational studies of depression that peripheral monocytes exhibit signs of glycolytic activation, better understanding the immunometabolic phenotypes of monocytes which are known to be elevated in MDD with high inflammation is a critical step toward comprehending and treating the impact of inflammation on the brain. This narrative review examines the extant literature on glycolytic metabolism of circulating monocytes in depression and discusses the functional implications of immunometabolic shifts at both cellular and systemic levels. Additionally, it proposes potential therapeutic applications of existing immunomodulators that target glycolysis and related metabolic pathways in order to reverse the impact of elevated inflammation on the brain and depressive symptoms.

A Meta-analysis of Different Acupuncture Modalities Combined With Antidepressants to Reduce Major Depressive Disorder.

Acupuncture is an effective therapy for depression. Nevertheless, the results of clinical studies on major depressive disorder (MDD) remain controversial. By November 2023, English-language published randomized clinical trials involving acupuncture for treating MDD were searched. The analysis comprised 9 studies with 809 subjects who met the eligibility criteria. The quality of the included studies was evaluated using the Quality in Prognostic Studies (QUIPS) tool. Acupuncture moderately alleviated the severity of MDD, independent of the method used (standardized mean difference [SMD] = -0.55; confidence interval [CI] 95%: -1.19, 0.09; P = 0.08). The severity of MDD was moderated by MA, regardless of antidepressant use (SMD = -0.49; CI95%: -1.13, 0.14, P = 0.09). Subgroup analysis revealed a nonsignificant reduction in MDD severity when using manual acupuncture alone (SMD -0.52; CI95%: -1.47, 0.44, P = 0.18). MDD severity was reduced by the use of manual acupuncture and antidepressants (SMD = -0.47; CI95%: -0.88, -0.06). Laser acupuncture and electroacupuncture (with or without antidepressants) did not significantly affect the severity of MDD. Manual acupuncture with or without antidepressants may alleviate the severity of MDD, but its clinical benefit for treating MDD is inconclusive.

Major depressive disorder and perceived social support: Moderated mediation model of security and brain dysfunction

Low social support increases the risk of Major depressive disorder (MDD), yet its effects on brain function are unclear. Thirty-two MDD patients with low social support, 52 with high social support, and 54 healthy controls were recruited. We investigated regional brain activity in MDD patients with low social support using resting-state functional Magnetic Resonance Imaging, employing measures such as degree centrality (DC), regional homogeneity, amplitude of low-frequency fluctuations, and fractional amplitude of low-frequency fluctuations. Abnormal regions identified in these analyses were selected as regions of interest for functional connectivity (FC) analysis. We then explored relationships among social support, brain dysfunction, MDD severity, and insecurity using partial correlation and moderated mediation models. Our findings reveal that MDD patients with low social support show decreased DC in the right superior temporal pole and right medial geniculate nucleus, coupled with increased FC between the right superior temporal pole and right inferior temporal gyrus, and the right supramarginal gyrus compared to those with high social support. Furthermore, the DC of the right medial geniculate nucleus positively correlates with social support, while the FC between the right superior temporal pole and right supramarginal gyrus negatively correlates with both social support and subjective support. Additionally, a moderated mediation model demonstrates that the FC between the right superior temporal pole and right supramarginal gyrus mediates the relationship between social support and depression severity, with security moderating this mediation. These findings underscore the impact of low social support on brain function and depression severity in MDD patients.

Prospective Associations Between Personality Traits and Major Depressive Disorder Symptom Severity: The Mediating Role of Illness Representations.

Major depressive disorder (MDD) patients' personality traits and illness representations are linked to MDD severity. However, the associations between personality and illness representations in MDD and the mediating role of illness representations between personality and MDD severity have not been investigated. This study aimed to prospectively investigate the aforementioned associations and the possible mediating role of illness representations between personality and MDD severity. One hundred twenty-five patients with a MDD diagnosis, aged 48.18 ± 13.92 (84% females), participated in the study. Personality traits were measured with the Traits Personality Questionnaire at baseline. Illness representations were measured with the Illness Perception Questionnaire-Mental Health about five months later (mean = 5.08 ± 1.14 months). MDD severity was measured about 10 months after the baseline assessment (mean = 9.53 ± 2.36 months) with the Beck Depression Inventory. SPSS 29 and AMOS 27 were used to conduct correlational and parallel mediation analyses. According to the results, Neuroticism was positively and Extraversion was negatively linked to MDD severity. Negative MDD impact representations fully mediated these associations. Neuroticism and Extraversion are linked to future MDD severity through patients' representations of MDD's impact. Restructuring maladaptive representations about MDD's impact can be a promising way to reduce symptom severity in patients with high Neuroticism and low Extraversion levels.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

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

Assessing the Relationship Between Vitiligo and Major Depressive Disorder Severity: Cross-Sectional Study.

Vitiligo, a common dermatological disorder in Saudi Arabia, is associated with significant psychological impacts. This study explores the relationship between vitiligo and the severity of major depressive disorder (MDD), highlighting the broader implications on mental health among affected individuals. We aim to assess the prevalence and predictors of depression among adult patients with vitiligo, and to examine the relationship between MDD severity and vitiligo. Using a cross-sectional design, the research used the vitiligo area severity index and the Patient Health Questionnaire-9 to measure the extent of vitiligo and depression severity, respectively. This study involved 340 diagnosed patients with vitiligo from various health care settings. Logistic and ordinal regression analysis were applied to evaluate the impact of sociodemographic variables and vitiligo types on MDD severity. The prevalence of MDD was 58.8% (200/340) of participants. Depression severity varied notably: 18.2% (62/340) of patients experienced mild depression, 17.9% (61/340) moderate, 11.8% (40/340) moderately severe, and 10.9% (37/340) severe depression. Female patients had higher odds of severe depression than male patients (adjusted odds ratio [aOR] 3.14, 95% CI 1.93-5.1; P<.001). Age was inversely related to depression severity, with patients aged older than 60 years showing significantly lower odds (aOR 0.1, 95% CI 0.03-0.39; P<.001). Lower income was associated with higher depression severity (aOR 10.2, 95% CI 3.25-31.8; P<.001). Vitiligo types also influenced depression severity; vulgaris (aOR 5.3, 95% CI 2.6-10.9; P<.001) and acrofacial vitiligo (aOR 2.8, 95% CI 1.5-5.1; P<.001) were significantly associated with higher depression levels compared to focal vitiligo. The findings suggest that vitiligo contributes to an increased risk of severe depression, highlighting the need for integrated dermatological and psychological treatment approaches to address both the physical and mental health aspects of the disease.

T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression

Major depressive disorder (MDD) is associated with T cell activation, but no studies have examined the combined effects of T cell activation and deficits in T regulatory (Treg) cells on the severity of acute phase MDD. Using flow cytometry, we determined the percentage and median fluorescence intensity of CD69, CD71, CD40L, and HLADR-bearing CD3+, CD4+, and CD8+ cells, and cannabinoid type 1 receptor (CB1), CD152 and GARP (glycoprotein A repetitions predominant)-bearing CD25+ FoxP3 T regulatory (Treg) cells in 30 MDD patients and 20 healthy controls in unstimulated and stimulated (anti-CD3/CD28) conditions. Based on cytokine levels, we assessed M1 macrophage, T helper (Th)-1 cell, immune-inflammatory response system (IRS), T cell growth, and neurotoxicity immune profiles. We found that the immune profiles (including IRS and neurotoxicity) were significantly predicted by decreased numbers of CD152 or GARP-bearing CD25+ FoxP3 cells or CD152 and GARP expression in combination with increases in activated T cells (especially CD8+ CD40L+ percentage and expression). MDD patients showed significantly increased numbers of CD3+ CD71+, CD3+ CD40L+, CD4+ CD71+, CD4+ CD40L+, CD4+ HLADR+, and CD8+ HLADR+ T cells, increased CD3+ CD71+, CD4+ CD71+ and CD4+ HLADR+ expression, and lowered CD25+ FoxP3 expression and CD25+ FoxP+ CB1+ numbers as compared with controls. The Hamilton Depression Rating Scale score was strongly predicted (between 30 and 40% of its variance) by a lower number of CB1 or GARP-bearing Treg cells and one or more activated T cell subtypes (especially CD8+ CD40L+). In conclusion, increased T helper and cytotoxic cell activation along with decreased Treg homeostatic defenses are important parts of MDD that lead to enhanced immune responses and, as a result, neuroimmunotoxicity.

Vitamin B12 and homocysteine in patients with major depressive disorder.

Alterations in the level of neurotransmitters are evident in patients with major depressive disorder (MDD). Vitamin B12 mediates the synthesis of neurotransmitters, and hence, vitamin B12 deficiency could be associated with depression. To assess the levels of serum vitamin B12, homocysteine (Hcy), and haematological profiles in patients of MDD. Fifty-nine patients with MDD were recruited based on ICD-10 criteria. Severity of depression was assessed by HAM-D scale. Vitamin B12, Hcy levels, and haematological profiles were analysed. Vitamin B12 was deficient or depleted in all patients with MDD. The median level of vitamin B12 in serum was 164.2 pg./ml and significantly lower in patients with severe MDD. The mean value of Hcy was 18.34 μmol/L, which was high compared to the normal reference range. The red cell distribution width (RDW-CV) varied significantly between the three groups of MDD patients. Patients consuming non-vegetarian food had a significantly higher median value of serum vitamin B12. Vitamin B12 deficiency is found in patients with MDD and varies inversely with severity of MDD. Hcy is found to be higher in patients with MDD. The manifestation of depressive symptoms precedes the more commonly known haematological manifestations of vitamin B12 deficiency in this study.

Polysomnographic parameters associated with cognitive function in patients with major depression and insomnia.

To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF. Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF. Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF. Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.