Severity Of Major Depressive Disorder Research Articles

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.

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.

The Humanistic and Economic Burden Associated with Major Depressive Disorder: A Retrospective Cross-Sectional Analysis.

Major depressive disorder (MDD) is a debilitating and costly condition. This analysis characterized the health-related quality of life (HRQoL), health care resource utilization (HCRU), and costs between patients with versus without MDD, and across MDD severity levels. The 2019 National Health and Wellness Survey was used to identify adults with MDD, who were stratified by disease severity (minimal/mild, moderate, moderately severe, severe), and those without MDD. Outcomes included HRQoL (Short Form-36v2 Health Survey, EuroQol Five-Dimension Visual Analogue Scale, utility scores), HCRU (hospitalizations, emergency department [ED] visits, health care provider [HCP] visits), and annualized average direct medical and indirect (workplace) costs. A subgroup analysis was conducted in participants with MDD and prior medication treatment failure. Participant characteristics and study outcomes were evaluated using bivariate analyses and multivariable regression models, respectively. Cohorts comprised 10,710 participants with MDD (minimal/mild = 5905; moderate = 2206; moderately severe = 1565; severe = 1034) and 52,687 participants without MDD. Participants with MDD had significantly lower HRQoL scores than those without (each comparison, P < 0.001). Increasing MDD severity was associated with decreasing HRQoL. Relative to participants without MDD, participants with MDD reported more HCP visits (2.72 vs 5.64; P < 0.001) and ED visits (0.18 vs 0.22; P < 0.001) but a similar number of hospitalizations. HCRU increased with increasing MDD severity. Although most patients with MDD had minimal/mild to moderate severity, total direct medical and indirect costs were significantly higher for participants with versus without MDD ($8814 vs $6072 and $5425 vs $3085, respectively, both P < 0.001). Direct and indirect costs were significantly higher across all severity levels versus minimal/mild MDD (each comparison, P < 0.05). Among patients with prior MDD medication treatment failure (n = 1077), increasing severity was associated with significantly lower HRQoL and higher total indirect costs than minimal/mild MDD. These results quantify the significant and diverse burdens associated with MDD and prior MDD medication treatment failure.

Comparative Analysis of Personality Traits in Major Depressive Disorder and Bipolar Disorder: Impact, Differences, and Associations with Symptoms.

This cross-sectional study aimed to compare the personality traits of patients with major depressive disorder (MDD) and bipolar disorder (BD) with those of healthy individuals. The goal was to gain insight into the potential impact of personality traits on the development and manifestation of mood disorders. One hundred seventy-eight patients with mood disorders were analyzed as either MDD or BD, with each group containing euthymic and depressive members: e-MDD, d-MDD, e-BD, and d-BD. Mood status was assessed using the Young Mania Rating Scale (YMRS), and the 17-item Hamilton Depression Rating Scale (HAMD-17). Ninety-five healthy individuals served as controls. Personality traits were assessed with the Eysenck Personality Questionnaire. The scores for neuroticism in the patient groups were comparable, but each group had higher scores compared to the control group (P < 0.001). Each patient group exhibited significantly lower scores for extraversion compared to the control group, with e-MDD, d-MDD, and d-BD showing particularly notable differences (P < 0.001); these groups scored significantly lower than the e-BD (P = 0.041, 0.009, 0.038). In patients with BD, there was an inverted association between extraversion score and HAMD total score (P = 0.010, r = -0.27), and a positive association with the YMRS total score (P = 0.022, r = 0.24). In the MDD group, there was a positive association between the neuroticism score and HAMD total score (P = 0.021, r = 0.25). Patients with mood disorders are characterized by lower extraversion and higher neuroticism. Level of neuroticism associated with depression severity in MDD. Patients with BD may be more extraverted, but their extraversion can be affected by depressive episodes. Extraversion may be a feature of BD, and may differentiate BD from MDD. Personality traits are related to disease diathesis and state, and shaped by symptom manifestations.

Serum indoleamine 2, 3-dioxygenase and tryptophan-2, 3-dioxygenase: potential biomarkers for the diagnosis of major depressive disorder.

The objective of this study was to observe the changes in the levels of indoleamine 2, 3-dioxygenase (IDO) and tryptophan-2, 3-dioxygenase (TDO) in patients with major depressive disorder (MDD) and investigate their potential role as novel biomarkers for diagnosing MDD. A total of 55 MDD patients and 55 healthy controls (HC) were enrolled in the study. The severity of MDD was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24) before and after treatment. The serum concentrations of IDO and TDO were measured at baseline and after treatment. The correlations between the serum levels of IDO and TDO and HAMD-24 scores were evaluated using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the area under the curve (AUC) of serum levels of IDO and TDO for discriminating MDD patients from HC. The serum IDO and TDO concentrations were significantly higher in patients with MDD at baseline than in healthy controls, and decreased significantly after 2weeks or 1month of treatment. The levels of IDO and TDO were significantly positively correlated with HAMD-24 scores. Furthermore, the AUC values for IDO and TDO were 0.999 and 0.966, respectively. The study suggests that serum IDO and TDO may serve as novel biomarkers for diagnosing MDD. These findings may lead to a better understanding of the pathogenesis of MDD and the development of new therapeutic targets.

Cortical glutamate, Glx, and total N-acetylaspartate: potential biomarkers of repetitive transcranial magnetic stimulation treatment response and outcomes in major depression

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for individuals with major depressive disorder (MDD) who have not improved with standard therapies. However, only 30–45% of patients respond to rTMS. Predicting response to rTMS will benefit both patients and providers in terms of prescribing and targeting treatment for maximum efficacy and directing resources, as individuals with lower likelihood of response could be redirected to more suitable treatment alternatives. In this exploratory study, our goal was to use proton magnetic resonance spectroscopy to examine how glutamate (Glu), Glx, and total N-acetylaspartate (tNAA) predict post-rTMS changes in overall MDD severity and symptoms, and treatment response. Metabolites were measured in a right dorsal anterior cingulate cortex voxel prior to a standard course of 10 Hz rTMS to the left DLPFC in 25 individuals with MDD. MDD severity and symptoms were evaluated via the Inventory of Depression Symptomatology Self-Report (IDS-SR). rTMS response was defined as ≥50% change in full-scale IDS-SR scores post treatment. Percent change in IDS-SR symptom domains were evaluated using principal component analysis and established subscales. Generalized linear and logistic regression models were used to evaluate the relationship between baseline Glu, Glx, and tNAA and outcomes while controlling for age and sex. Participants with baseline Glu and Glx levels in the lower range had greater percent change in full scale IDS-SR scores post-treatment (p < 0.001), as did tNAA (p = 0.007). Low glutamatergic metabolite levels also predicted greater percent change in mood/cognition symptoms (p ≤ 0.001). Low-range Glu, Glx, and tNAA were associated with greater improvement on the immuno-metabolic subscale (p ≤ 0.003). Baseline Glu predicted rTMS responder status (p = 0.025) and had an area under the receiving operating characteristic curve of 0.81 (p = 0.009), demonstrating excellent discriminative ability. Baseline Glu, Glx, and tNAA significantly predicted MDD improvement after rTMS; preliminary evidence also demonstrates metabolite association with symptom subdomain improvement post-rTMS. This work provides feasibility for a personalized medicine approach to rTMS treatment selection, with individuals with Glu levels in the lower range potentially being the best candidates.

Elevated depression and anxiety predict future patterns of individualistic and collectivistic cultural values: A cross-lagged longitudinal network analysis

BackgroundSpecific components of independent and interdependent self-construal have been associated with psychopathology. However, most studies on this topic have been cross-sectional, precluding causal inferences. We used contemporaneous and temporal cross-lagged network analysis to establish weak causal effects in understanding the association between self-construal and psychopathology components. MethodsMiddle-aged and older community-dwelling adults (n = 3294) participated in the Midlife Development in the United States study across two time-points, spaced nine years apart. Six self-construal (interdependence: connection to others, commitment to others, receptiveness to influence; independence: behavioral consistency, sense of difference from others, self-reliance) and three psychopathology nodes (major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) symptom severity) were examined. All network analyses controlled for age, sex, race, and number of chronic illnesses as covariates. ResultsContemporaneous and temporal networks yielded relations between elevated MDD and PD and increased receptiveness to influence. Heightened GAD symptom severity was associated with future increased difference from others and decreased connection to others, commitment to others, and receptiveness to influence. Higher MDD, GAD, and PD severity were associated with future lower self-reliance. Network comparison tests revealed no consistent network differences across sex and race. LimitationsDSM-III-R measures of MDD, GAD, and PD were used. Results may not generalize to culturally diverse racial groups. ConclusionsChanges in self-construal may result from increased MDD, GAD, and PD severity. Findings suggest the importance of targeting common mental health symptoms to positively influence how individuals view the self and others in various social contexts.

Genome-wide transcriptomic and biochemical profiling of major depressive disorder: Unravelling association with susceptibility, severity, and antidepressant response

Identifying biomarkers for diagnosing Major Depressive Disorder (MDD), assessing its severity, and guiding treatment is crucial. We conducted whole genome transcriptomic study in North Indian population, and analyzed biochemical parameters. Our longitudinal study investigated gene-expression profiles from 72 drug-free MDD patients and 50 healthy controls(HCs) at baseline and 24 patients after 12-weeks of treatment. Gene expression analyses identified differentially expressed genes(DEGs) associated with MDD susceptibility, symptom severity and treatment response, independently validated by qPCR. Hierarchical clustering revealed distinct expression patterns between MDD and HCs, also between mild and severe cases. Enrichment analyses of significant DEGs revealed inflammatory, apoptosis, and immune-related pathways in MDD susceptibility, severity, and treatment response. Simultaneously, we assessed thirty biochemical parameters in the same cohort, showed significant differences between MDD and HCs in 13 parameters with monocytes, eosinophils, creatinine, SGPT, and total protein remained independent predictors of MDD in a multivariate-regression model. Our study supports the role of altered immune/inflammatory signaling in MDD pathophysiology, offering clinically relevant biochemical parameters and insights into transcriptomic gene regulation in MDD pathogenesis and treatment response.

Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study

BackgroundSocial anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined. Methods85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables. ResultsA significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: −0.006, 95 % CI: −0.0108 – −0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables. ConclusionsBased on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia.

Analysis of EEG features and study of automatic classification in first-episode and drug-naïve patients with major depressive disorder.

Major depressive disorder (MDD) has a high incidence and an unknown mechanism. There are no objective and sensitive indicators for clinical diagnosis. This study explored specific electrophysiological indicators and their role in the clinical diagnosis of MDD using machine learning. Forty first-episode and drug-naïve patients with MDD and forty healthy controls (HCs) were recruited. EEG data were collected from all subjects in the resting state with eyes closed for 10min. The severity of MDD was assessed by the Hamilton Depression Rating Scale (HAMD-17). Machine learning analysis was used to identify the patients with MDD. Compared to the HC group, the relative power of the low delta and theta bands was significantly higher in the right occipital region, and the relative power of the alpha band in the entire posterior occipital region was significantly lower in the MDD group. In the MDD group, the alpha band scalp functional connectivity was overall lower, while the scalp functional connectivity in the gamma band was significantly higher than that in the HC group. In the feature set of the relative power of the ROI in each band, the highest accuracy of 88.2% was achieved using the KNN classifier while using PCA feature selection. In the explanatory model using SHAP values, the top-ranking influence feature is the relative power of the alpha band in the left parietal region. Our findings reveal that the abnormal EEG neural oscillations may reflect an imbalance of excitation, inhibition and hyperactivity in the cerebral cortex in first-episode and drug-naïve patients with MDD. The relative power of the alpha band in the left parietal region is expected to be an objective electrophysiological indicator of MDD.

A Comparative Efficacy of Antidepressants in the Treatment of Major Depressive Disorder: A Systematic Review and Meta-Analysis

Major Depressive Disorder (MDD) affects about 280, 000, 000 people globally, with a higher incidence among females than males. The increasing incidence implicates health burdens and clinical dilemmas regarding the low efficacy of the existing antidepressants. A literature search was performed on electronic databases, PubMed, the Cochrane Library of Randomized Trials, Scopus, and ProQuest, for studies reporting the efficacy of an SNRI (Desvenlafaxine 50 mg/d), a serotonin modulator (Vortioxetine 10-20 mg/d), and an aminoketone antidepressant (Bupropion). Study selection focused on randomized controlled trials (RCTs) and observational studies. All statistical analyses and visualization were performed using the Review Manager (RevMan) software and Python programming. The random effects model, ANOVA test, and Cohen’s d were used for statistical analyses. The present meta-analysis involved 17 studies, including 11, 533 participants. The results aligned with previous studies and accounts provided by literature regarding the efficacy of antidepressants used to manage MDD. Five studies, including 2, 377 MDD patients, reported a statistically significant outcome, that Desvenlafaxine 50 mg/d reduced MDD’s severity than placebo (OR: 0.52, 95% CI [0.44, 0.62], P &lt; 0.00001, I2 = 0%). Three studies involving 742 MDD patients reported the efficacy of dextromethorphan-bupropion (AXS-50). The reduction of MADRS scores in the treatment group was statistically insignificant, with high variability, favouring the placebo (OR of 1.85 [95% CI: 0.93, 3.70], p = 0.08, I2 = 79%). Additionally, Vortioxetine 10-20 mg/d produced adverse effects, headache, vomiting, nausea, diarrhea, dizziness, nasopharyngitis, somnolence, and suicidal ideation among 6, 669 MDD patients reported by the 9 studies. The finding was statistically significant but with a high variability OR: 15.25, 95% CI [12.55, 18.52], P &lt; 0.00001, I2 = 98%). A preliminary analysis of evidence collected following Desvenlafaxine, AXS-50, and Vortioxetine administration yielded compelling evidence on the efficacy of antidepressants in MDD treatment. Desvenlafaxine and AXS-50 reported reduced severity and symptomatology in MDD, respectively. On the other hand, Vortioxetine implicated adverse effects, which are common with most antidepressants. Despite adverse effects like headache, vomiting, nausea, diarrhea, dizziness, nasopharyngitis, somnolence, and suicidal ideation, antidepressants used to treat MDD yield clinically satisfying outcomes like decreased severity of depression and relief from symptoms. Clinicians should monitor patients to take care of any adverse effects resulting from the treatments. Keywords: Antidepressant efficacy, adverse effects, major depressive disorder, MDD symptomatology, severity, improved outcomes.

A Comparative Efficacy of Antidepressants in the Treatment of Major Depressive Disorder: A Systematic Review and Meta-Analysis

Study background &amp; objective: Major Depressive Disorder (MDD) affects about 280, 000, 000 people globally, with a higher incidence among females than males. The increasing incidence implicates health burdens and clinical dilemmas regarding the low efficacy of the existing antidepressants. Methods: A literature search was performed on electronic databases, PubMed, the Cochrane Library of Randomized Trials, Scopus, and ProQuest, for studies reporting the efficacy of an SNRI (Desvenlafaxine 50 mg/d), a serotonin modulator (Vortioxetine 10-20 mg/d), and an aminoketone antidepressant (Bupropion). Study selection focused on randomized controlled trials (RCTs) and observational studies. All statistical analyses and visualization were performed using the Review Manager (RevMan) software and Python programming. The random effects model, ANOVA test, and Cohen’s d were used for statistical analyses. Results: The present meta-analysis involved 17 studies, including 11, 533 participants. The results aligned with previous studies and accounts provided by literature regarding the efficacy of antidepressants used to manage MDD. Five studies, including 2, 377 MDD patients, reported a statistically significant outcome, that Desvenlafaxine 50 mg/d reduced MDD’s severity than placebo (OR: 0.52, 95% CI [0.44, 0.62], P &lt; 0.00001, I2 = 0%). Three studies involving 742 MDD patients reported the efficacy of dextromethorphan-bupropion (AXS-50). The reduction of MADRS scores in the treatment group was statistically insignificant, with high variability, favouring the placebo (OR of 1.85 [95% CI: 0.93, 3.70], p = 0.08, I2 = 79%). Additionally, Vortioxetine 10-20 mg/d produced adverse effects, headache, vomiting, nausea, diarrhea, dizziness, nasopharyngitis, somnolence, and suicidal ideation among 6, 669 MDD patients reported by the 9 studies. The finding was statistically significant but with a high variability OR: 15.25, 95% CI [12.55, 18.52], P &lt; 0.00001, I2 = 98%). Discussion: A preliminary analysis of evidence collected following Desvenlafaxine, AXS-50, and Vortioxetine administration yielded compelling evidence on the efficacy of antidepressants in MDD treatment. Desvenlafaxine and AXS-50 reported reduced severity and symptomatology in MDD, respectively. On the other hand, Vortioxetine implicated adverse effects, which are common with most antidepressants. Conclusion: Despite adverse effects like headache, vomiting, nausea, diarrhea, dizziness, nasopharyngitis, somnolence, and suicidal ideation, antidepressants used to treat MDD yield clinically satisfying outcomes like decreased severity of depression and relief from symptoms. Clinicians should monitor patients to take care of any adverse effects resulting from the treatments.

A - 126 Cognitive Performance in Individuals with Major Depressive Disorder and no Diagnosis.

To compare performance in neuropsychological assessments between a sample of individuals with Major Depressive Disorder (MDD) and those with no diagnosis. The MDD group (n = 77; Mage = 34.69, SD = 12.80; Med =13.41, SD = 2.45) had 41.6% male, 69.7% White, 10.5% Black, 17.1% Hispanic, and 2.6% other race). The undiagnosed group (n = 83, Mage = 33.39, SD = 11.82; Med =13.62, SD = 3.02) had 56.6% male, 56.6% White, 18.1% Black, 16.9% Hispanic, and 8.4% other. Participants were selected from a de-identified outpatient clinical database. The groups did not differ significantly in age, years of education, race, or gender (p values >0.05). No significant differences were found in intellectual functioning or memory ability as measured by the WAIS-IV and WMS-IV, respectively (p values >0.05). At the group level, individuals diagnosed with MDD completed significantly fewer categories [t(137) = -2.15, p = 0.02] and made more errors [t(137) = 1.99, p = 0.02] and perseverative responses [t(135) = 2.66, p = 0.004] on the WCST than undiagnosed participants. The increased number of errors and perseverative responses among individuals with MDD might be associated with difficulties sustaining attention, set-shifting, and abstract concept formation associated with depression. As expected, we did not observe differences in recognition memory or intellectual functioning, which tend to remain stable in the presence of mood disorders. Limitations of our study include the lack of a premorbid measure of intellectual functioning and MDD severity. Future research could explore the effect of MDD severity on cognitive performance.

Changes in comorbid depression following intensive trauma-focused treatment for PTSD and complex PTSD

ABSTRACT Background: The extent to which intensive trauma-focused treatment for individuals with post-traumatic stress disorder (PTSD) is also effective in treating comorbid major depressive disorder (MDD) remains unclear. Objective: The purpose of the present study was to test the hypothesis that brief intensive trauma-focused therapy for PTSD is associated with significant reductions in depressive symptoms and loss of diagnostic status of MDD. Methods: A total of 334 adult patients with PTSD (189 patients who were also diagnosed with MDD) underwent a brief intensive trauma-focused treatment programme consisting of EMDR therapy, prolonged exposure, physical activity, and psychoeducation. At pre-treatment, post-treatment and 6-month follow-up, severity and diagnostic status of PTSD and MDD were assessed. A linear mixed model was used to analyze changes in the severity of PTSD and depressive symptoms, whereas a generalized linear mixed model was used to determine changes in the MDD diagnostic status. Results: Treatment resulted in a significant and strong decrease of PTSD and MDD symptoms at post-treatment (d = 2.34 and 1.22, respectively), and at 6-month follow-up (d = 1.67 and 0.73, respectively). The proportion of patients fulfilling the diagnostic status of MDD changed from 57% at pre-treatment to 33% at the 6-month follow-up. Although the initial response to treatment did not differ between patients with and without comorbid MDD, for both groups a significant relapse in depressive symptoms was found after six months, which could be explained almost entirely by the presence of CPTSD at baseline. Conclusions: The results support the notion that brief, intensive trauma-focused treatment is highly effective for individuals with PTSD and comorbid MDD. Because patients with CPTSD are vulnerable to relapse in depressive symptoms, this target group may require additional treatment.

Discovery and validation of a protein biomarker for the diagnosis and classification of disease severity of major depressive disorder

Background and aimsDiagnosis and classification of disease severity of major depressive disorder (MDD) are determined through a doctor’s consultation and questionnaire-based rating scale. This study aimed to identify and validate a serum protein biomarker for diagnosing and classifying the disease severity of MDD. Materials and methodsBased on the Hamilton Depression Rating Scale (HAMD) score, participants were divided into control, mild, moderate, and severe groups. Samples prepared from collected sera were analyzed using non-targeted qualitative and targeted quantitative tools to identify potential biomarkers. ResultsFour proteins were selected as biomarker candidates, which showed statistically significant consistent tendencies depending on MDD severity. Among them, tetranectin was the only validated protein in the quantitative analysis that showed the same decreasing tendency as that in the qualitative analysis. Furthermore, tetranectin showed fair discrimination performance between the control and MDD group. ConclusionsTetranectin may be a novel potential biomarker for diagnosing and classifying the severity of MDD, though further verification and validation studies of its efficacy are needed

Effects of childhood neglect on regional brain activity and corresponding functional connectivity in major depressive disorder and healthy people: Risk factor or resilience?

BackgroundChildhood neglect is a high risk factor for major depressive disorder (MDD). However, the effects of childhood neglect on regional brain activity and corresponding functional connectivity in MDD patients and healthy populations remains unclear. MethodsRegional homogeneity, amplitude of low-frequency fluctuations (ALFF), fractional ALFF, degree centrality, and voxel-mirrored homotopic connectivity were extensively calculated to explore intraregional brain activity in MDD patients with childhood neglect and in healthy populations with childhood neglect. Functional connectivity analysis was then performed using regions showing abnormal brain activity in regional homogeneity/ALFF/fractional ALFF/degree centrality/voxel-mirrored homotopic connectivity analysis as seed. Partial correlation analysis and moderating effect analysis were used to explore the relationship between childhood neglect, abnormal brain activity, and MDD severity. ResultsWe found decreased brain function in the inferior parietal lobe and cuneus in MDD patients with childhood neglect. In addition, we detected that childhood neglect was significant associated with abnormal cuneus brain activity in MDD patients and that abnormal cuneus brain activity moderated the relationship between childhood neglect and MDD severity. In contrast, higher brain function was observed in the inferior parietal lobe and cuneus in healthy populations with childhood neglect. ConclusionsOur results provide new evidence for the identification of neural biomarkers in MDD patients with childhood neglect. More importantly, we identify brain activity characteristics of resilience in healthy populations with childhood neglect, providing more clues to identify neurobiological markers of resilience to depression after suffering childhood neglect.

Intolerance of uncertainty, perfectionism, and coping as predictors of depression diagnosis and severity

Major Depressive Disorder (MDD) is the leading cause of disability worldwide, affecting 3.8% of the global population. Despite its prevalence, less than half of those diagnosed with MDD receive treatment and remission rates remain low. Given these poor outcomes for individuals with depression and the findings of our previous study examining the role of certain psychological phenomena on the incidence of obsessive-compulsive disorder (OCD), the present study aims to examine whether intolerance of uncertainty, perfectionism, and coping strategies can together predict the diagnosis and severity of MDD. Participants were outpatients (N = 549) referred to a tertiary care clinic in Toronto, Canada between 2011 and 2014. After undergoing a diagnostic assessment, participants were administered a series of self-report questionnaires that measured intolerance of uncertainty, perfectionism, and coping. Results demonstrate that task-oriented coping and emotion-oriented coping significantly predicted depression diagnosis, while avoidant coping, perfectionism, and intolerance of uncertainty did not. As for depression severity, significant predictors included perfectionism, task-oriented coping, emotion-oriented coping, and avoidant coping. Further research is needed to identify interactions between the subscales of these constructs to determine how they work in tandem to influence MDD. Our findings indicate a need for more personalized interventions in the treatment of this disorder.

Correlation of Severity of Depression with a Novel Inflammatory Marker: Neutrophil to Lymphocyte Ratio

Introduction: Many new inflammatory markers are being extensively used recently for assessing the severity and prognosis of chronic conditions. Neutrophil-Lymphocyte ratio (NLR) because of its simplicity and affordability stands out. Its applicability to psychiatric disorders specifically Depression is an eye-opener. Hamilton Rating Scale for Depression (HAM-D), a clinician-based scoring system is better among other self-scoring systems where the study population is semi-illiterate. Materials and Method: Total of 80 patients over a period of 1 year presenting to psychiatric OPD with depressive symptoms were evaluated for the severity of Major Depressive Disorder (MDD) using HAM-D scale. A score of 7-17, 18-24 and &gt;25 was categorised under mild, moderate, and severe degrees respectively. NLR was calculated and was correlated with their severity. Statistical analysis was done using PSPP software and p value of &lt;0.05 was considered significant. Results: Out of the 80 patients 45 were females and 35 were males. The average age was 35.41 years ± 10.13 SD. 23 patients categorised under mild depression had mean NLR of 1.56 ± 0.46 SD, 40 patients with moderate depression and 17 patients with severe depression had mean NLR of 2.70 ± 1.08 SD and 4.62 ± 1.31 SD respectively. The mean value of NLR for patients of severe depression lied in the Mild-Moderate Inflammation zone (3-7). P-value was &lt;0.05 and was considered significant. Discussion: A novel and easy biomarker like NLR can be as useful as assessing Inflammatory Cytokines like IL-6, IL-1 and TNF-α for assessing the severity of MDD. Rise of cortisol in persistent stress favours an increase in neutrophils and a reduction in lymphocytes, and thus, increased NLR. Thus, a rise of NLR with increasing severity of Depression could become a robust tool in future for predicting mortality and severity in patients suffering from MDD.

Structural Relationship of Psychiatric Disorders, Quality of Life, Coping Styles and Their Associated Factors Among Brain Pathology Patients and Hematological Cancer Patients

Introduction: The study aimed to examine the structural relationship of major depressive disorder (MDD), anxiety disorder, various mental diseases, quality of life, coping methods, and other variables in patient with brain pathology and hematological cancer patients. Methods: A total of (n=215) samples were included in the structural equation modeling (SEM) analyses. The analyses were done with brain pathology patients (110) and haematological cancer patients (105). Results: In the current study, the multivariate normality kurtosis was 9.112 with c.r = 3.950 obtained in this SEM model. In the SEM model, the global health status towards MDD can explain about 30% of the variance. The global health status score was found to have a significant positive association with self-distraction coping styles, gender, and emotional functioning. Gender has a significant positive association with global health status, indicating that male patients have improved overall health. In terms of severity of MDD the positive correlation was found with panic disorder life time. Emotional functioning, self distraction and global health status were shown to have a significant and inverse relationship with the severity of MDD (p&lt;0.05). Conclusion: The severity of MDD was found to have a strong and detrimental association with cancer types indicating the brain pathology patients tends to have more severity of depression compared to haematological cancer patients.

The clinical, economic, and patient-centric burden of insomnia symptom severity in adults with major depressive disorder in the United States.

Insomnia is prevalent in adults with major depressive disorder (MDD) and is a key diagnostic criterion of MDD; however, little is understood about the burden of insomnia symptom severity in MDD. We evaluated the relationship between insomnia symptom severity and the clinical, economic, and patient-centric burden among community-dwelling individuals with MDD. Respondents with diagnosed depression who reported insomnia symptoms in the past 12 months (N=4402) were identified from the 2019 United States National Health and Wellness Survey. Multivariable analyses assessed the association of Insomnia Severity Index (ISI) with health-related outcomes while controlling for sociodemographic and health characteristics. Further analyses also controlled for depression severity (9-item Patient Health Questionnaire). Mean ISI score was 14.3±5.6. Higher ISI was associated with greater depression severity (r=.51, p<.001). After adjustments, a one-standard deviation (5.6-point) increase in ISI score was significantly associated with higher depression (rate ratio [RR]=1.36), anxiety (RR=1.33) and daytime sleepiness (RR=1.16) levels, more healthcare provider (RR=1.13) and emergency room visits (RR=1.31), hospitalizations (RR=1.21), work productivity and activity impairment (RRs=1.27 and 1.23, respectively), and poorer mental and physical health-related quality of life (β=-3.853 and -1.999, respectively) (p<.001). These findings remained statistically significant when controlling for concurrent depression severity. In adults with MDD, greater insomnia symptom severity is associated with worse health-related outcomes, which suggests the importance of addressing insomnia symptoms as a clinical target for treating MDD.