Diagnosis Of Major Depressive Disorder Research Articles

Cause-specific mortality in treatment-resistant major depression: Population-based cohort study

BackgroundLimited evidence-base on long-term prognosis of treatment-resistant major depression (TRD) is a barrier to clinical decision-making. Therefore, the purpose of this study was to establish cause-specific mortality in TRD compared to non-TRD major depression. MethodWe identified all individuals with a diagnosis of major depression (MDD) who were treated with an antidepressant aged 15 to 65 years during 2004–2016 in Finland. Persons with over two treatment trials were defined to have TRD. Data were analysed with Cox proportional hazard models. Results176,942 individuals with MDD (63 % women, median age at index diagnosis 40 years), of whom 11 % (n = 19,305) fulfilled the TRD criteria, were followed-up for 1,525,646 person-years (median 8.9 years). There were 959 deaths (6.1 deaths/1000 person-years) in TRD and 7662 deaths (5.6/1000 person-years) in non-TRD. All-cause mortality was 17 % higher (adjusted hazard ratio (aHR), 1.17; 95 % confidence interval (CI), 1.09–1.25) in TRD compared to non-TRD, when sex and age at index antidepressant prescription were controlled for. In TRD, increased mortality was observed for suicides (aHR, 1.90; 95%CI, 1.64–2.20) and for accidental poisonings (aHR, 1.81; 95%CI, 1.48–2.22), but not for natural causes (aHR, 0.98; 95%CI, 0.90–1.07). A higher proportion of accidental drug overdoses was observed in TRD than in non-TRD (62 % vs 42 %, respectively). LimitationsDefinition of TRD lacks consensus. We used routine data to define TRD. ConclusionsThe markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression.

Plasma alpha-trypsin inhibitor heavy chain 4 as an age-specific biomarker in the diagnosis and treatment of major depressive disorder

Plasma alpha-trypsin inhibitor heavy chain 4 as an age-specific biomarker in the diagnosis and treatment of major depressive disorder

The impact of solid fuel use on major depression and the buffering effect of outdoor time in the UK adults: A 12-year cohort study

BackgroundThis study aims to investigate age- and gender-specific effects of household solid fuels for heating on major depression and buffering effects of outdoor time in a high-income country. MethodsData were obtained from the UK Biobank. Participants with complete information on our studied variables and no prior diagnosis of major depression at baseline were included. Cox proportional hazards regression models were used to examine the effects of household solid fuels for heating on major depression. Subgroup analyses were conducted to investigate the buffering effects of outdoor time in summer and winter. Sensitivity analyses were performed to test the robustness of the main findings. ResultsOf 255,505 participants (50.2 % women), the 12-year cumulative incidence of major depression was 4.4 %. Household solid fuels for heating increased the risk of major depression only in women aged <45 years (HR (95%CI) = 1.30 (1.04, 1.63)). In this group, the solid fuel effect was moderated by outdoor time spending both in summer (HR (95%CI), ≤2 h/day: 1.61 (1.13, 2.28); >2 h/day: 1.13 (0.84, 1.52)) and winter (≤1 h/day: 1.35 (1.01, 1.08); >1 h/day: 1.24 (0.86, 1.77)). LimitationsSelf-reported measures might lead to recall bias and some potential confounders, such as ventilation efficiency, were not measured and controlled in data analyses. ConclusionsYounger women are more vulnerable to the impact of domestic air pollution on major depression. Promoting outdoor activities is a cost-effective and efficient approach to mitigating the risk of major depression caused by household solid fuels.

Herpes simplex reactivation triggers symptom exacerbation in patients with major depressive disorder

BackgroundHerpes Simplex Virus (HSV) infection has been linked to depression, but the underlying mechanism remains largely unknown. We hypothesized that recurring HSV infection could exacerbate depressive symptomatology via activation of the immune response and the kynurenine pathway in patients with Major Depressive Disorder (MDD). Methods32 MDD patients and 17 psychiatrically healthy individuals with a history of HSV recurrence were enrolled into the study. Blood samples were obtained, and psychiatric symptom severity was assessed at three separate visits- asymptomatic, active infection, and follow-up. Plasma levels of tryptophan metabolite levels were measured using ultra-high performance liquid chromatography-mass spectrometry (LC-MS), and inflammation-associated proteins were measured using high sensitivity electrochemiluminescence. ResultsThere was a significant effect of infection recurrence on IFN-γ and sICAM-1 levels, the latter being influenced by MDD diagnosis. This indicates that the effect of infection on sICAM-1 levels differs between control and depressed groups, although post hoc analysis suggests that interaction effect might be subtle. Infection recurrence had a significant effect on the reactivity of psychiatric symptoms. Finally, there was a positive correlation between levels of anti-inflammatory cytokines IL-10 and IL-13 and depression severity in the cohort during infection recurrence. LimitationsRelatively small sample size, limited number of male participants, and the relatively weak inflammatory stimuli studied. ConclusionsMDD patients might react with an exacerbation of symptoms along with elevations of inflammatory markers during HSV recurrence. Further, the association with symptom severity indicates that therapeutic modulation of inflammation may be beneficial in patients with MDD, especially during active infections.

Neuropsychological performance in women at risk of postpartum depression and postpartum psychosis.

While neuropsychological deficits are commonly observed in affective and psychotic disorders, this remains unexplored in these disorders when they occur during pregnancy and the postpartum period. A neuropsychological test battery was administered to women defined at risk of postpartum depression (PD, N = 53) because having either a current or past diagnosis of major depressive disorder, women at risk of postpartum psychosis (PP, N = 43) because of a diagnosis of bipolar disorder or schizoaffective disorder and/or a previous episode of PP and women not at risk (NR, N = 48) in the third trimester of pregnancy. Generalized and specific cognitive abilities were compared between groups. Women at risk of PP presented worse executive functions and processing speed compared to NR and worse performance compared to women at risk of PD across all cognitive domains. In addition, women at risk of PP who developed a psychiatric relapse in the first four weeks post-partum showed worse verbal learning and memory, visual memory, executive functions and processing speed in pregnancy compared to NR, whereas women at risk of PP who remained well presented neuropsychological performance that was intermediate between that of the women NR and those at risk of PP who developed symptoms. There were no differences in performance between women at risk of PD and the NR women, even if 31 women at risk of PD presented depressive symptoms at the time of cognitive assessment. Our findings in women at risk of PP align with neuropsychological findings in individuals with, or at risk of psychosis unrelated to pregnancy. In addition, initial evidence that women at risk of PP who develop a psychiatric relapse in the postpartum show a particularly poor neuropsychological performance in pregnancy suggests that this could be considered part of a phenotype for the disease and help guiding future preventive strategies in this clinical population. In women at risk of PD, the presence of depressive symptoms did not influence cognitive performance.

Hippocampal, thalamic, and amygdala subfield morphology in major depressive disorder: an ultra-high resolution MRI study at 7-Tesla.

Morphological changes in the hippocampal, thalamic, and amygdala subfields have been suggested to form part of the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented in-depth examinations at the subfield level, precluding a fine-grained understanding of these subfields and their involvement in MDD pathophysiology. We uniquely employed ultra-high field MRI at 7.0 Tesla to map hippocampal, thalamic, and amygdala subfields in MDD. Fifty-six MDD patients and 14 healthy controls (HCs) were enrolled in the final analysis. FreeSurfer protocols were used to segment hippocampal, thalamic, and amygdala subfields. Bayesian analysis was then implemented to assess differences between groups and relations with clinical features. While no effect was found for MDD diagnosis (i.e., case-control comparison), clinical characteristics of MDD patients were associated with subfield volumes of the hippocampus, thalamus, and amygdala. Specifically, the severity of depressive symptoms, insomnia, and childhood trauma in MDD patients related to lower thalamic subfield volumes. In addition, MDD patients with typical MDD versus those with atypical MDD showed lower hippocampal, thalamic, and amygdala subfield volumes. MDD patients with recurrent MDD versus those with first-episode MDD also showed lower thalamic subfield volumes. These findings allow uniquely fine-grained insights into hippocampal, thalamic, and amygdala subfield morphology in MDD, linking some of them to the clinical manifestation of MDD.

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 effect of intranasal (R,S)-ketamine on symptoms of fatigue in severe major depressive disorder or bipolar depression with and without comorbid alcohol use disorder: Results from a randomized, double-blind, placebo-controlled trial

BackgroundFatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD). MethodsTwenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment. ResultsThe group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects. LimitationsLimitations include the limited sample size, short duration, and single, fixed dose. ConclusionsIN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions.

Identification of Pyroptosis-Related Molecular Subtypes and Diagnostic Model development in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent psychological disorder associated with inflammation, with complex pathological mechanisms. Pyroptosis has been suggested to contribute to inflammation in central nervous system diseases. Little research, however, has examined what role pyroptosis played in MDD. In the present study, the differential expression pyroptosis-related genes (DE-PRGs) in MDD were identified from the GEO database (GSE98793 and GSE19738). Then, consensus clustering analysis was used to evaluate differences in MDD molecular subtypes characteristics based on PRGs. The characteristic diagnostic biomarkers for MDD were identified by Weighted Correlation Network Analysis (WGCNA) and multiple machine learning algorithms. Three intersection genes (GZMA, AKR1C3, and CD52) were obtained, which are expected to become potential biomarkers for MDD with excellent reliability and accuracy. Subsequently, the immune infiltration characteristics result indicated that the development of MDD is mediated by immune-related function, where three DE-PRGs were strongly related to the immune infiltration landscape of MDD. The biological experiments in vitro further proved that three unique PRGs are emerging as important players in MDD diagnosis. Our research aimed to provide novel ideas and biomarkers targeting MDD.

Evaluating the Efficacy of a Digital Therapeutic (CT-152) as an Adjunct to Antidepressant Treatment in Adults With Major Depressive Disorder: Protocol for the MIRAI Remote Study.

Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. This study aimed to describe a phase 3 remote, multicenter, randomized, masked, sham-controlled trial evaluating the efficacy of a smartphone app-based DTx (CT-152) in adult participants diagnosed with MDD, used as an adjunct to antidepressant therapy (ADT). Participants aged 22-64 years with a current primary diagnosis of MDD and an inadequate response to ADT were included. Participants were randomized 1:1 to CT-152 or a sham DTx. CT-152 is a smartphone app-based DTx that delivers a cognitive-emotional and behavioral therapeutic intervention. The core components of CT-152 are the Emotional Faces Memory Task exercises, brief lessons to learn and apply key therapeutic skills, and SMS text messaging to reinforce lessons and encourage engagement with the app. The sham DTx is a digital working memory exercise with emotionally neutral stimuli designed to match CT-152 for time and attention. Participants took part in the trial for up to 13 weeks. The trial included a screening period of up to 3 weeks, a treatment period of 6 weeks, and an extension period of 4 weeks to assess the durability of the effect. Sites and participants had the option of an in-person or remote screening visit; the remaining trial visits were remote. Efficacy was evaluated using the Montgomery-Åsberg Depression Rating Scale, the Generalized Anxiety Disorder-7, Clinical Global Impression-Severity scale, the Patient Health Questionnaire-9, and the World Health Organization Disability Assessment Schedule 2.0. The durability of the effect was evaluated with the Montgomery-Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scale. Adverse events were also assessed. Satisfaction, measured by the Participant and Healthcare Professional Satisfaction Scales, and health status, measured by the EQ-5D-5L, were summarized using descriptive statistics. This study was initiated in February 2021 and had a primary completion date in October 2022. This represents the methodological design for the first evaluation of CT-152 as an adjunct to ADT. This study protocol is methodologically robust and incorporates many aspects of conventional pivotal pharmaceutical phase 3 trial design, such as randomization and safety end points. Novel considerations included the use of a sham comparator, masking considerations for visible app content, and outcome measures relevant to DTx. The rigor of this methodology will provide a more comprehensive understanding of the effectiveness of CT-152. ClinicalTrials.gov NCT04770285; https://clinicaltrials.gov/study/NCT04770285. RR1-10.2196/56960.

Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials.

Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice.

Multichannel tDCS with advanced targeting for major depressive disorder: a tele-supervised at-home pilot study.

Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies. https://clinicaltrials.gov/study/NCT05205915?tab=results, identifier NCT05205915.

Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.

Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen's d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß=0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß=-0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß=0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.

Intolerance of uncertainty on distress and impairment: The mediating role of repetitive negative thinking.

Repetitive negative thinking and intolerance of uncertainty are risk and maintenance factors for emotional disorders. Although emerging evidence suggests that intolerance of uncertainty predicts increases in distress through repetitive negative thinking, these relationships have yet to be investigated among veterans. The present study examines if repetitive negative thinking mediates the relationships of intolerance of uncertainty with stress, disordered symptoms and impairment among a mixed clinical sample of veterans. Two hundred and forty-four treatment-seeking veterans with diagnoses of major depressive disorder, panic disorder, or posttraumatic stress disorder completed measures of intolerance of uncertainty, repetitive negative thinking, stress, impairment, depression, panic, and posttraumatic stress prior to receiving treatment. Mediation models revealed indirect effects of intolerance of uncertainty through repetitive negative thinking on stress and impairment in the full sample, and on disordered symptoms in subsamples with major depressive disorder and posttraumatic stress disorder. Conversely, intolerance of uncertainty did not have direct or indirect effects on disordered symptoms in a panic disorder subsample. Findings suggest that repetitive negative thinking and intolerance of uncertainty uniquely contribute to stress, impairment, and disordered symptoms, but repetitive negative thinking, may, in part, drive intolerance of uncertainty's contribution to emotional disorders. Interventions for repetitive negative thinking might improve the efficacy of existing transdiagnostic treatment protocols. Cross-sectional data is a limitation of the present study. Prospective designs in civilian samples can better establish the temporality of these relationships and if they are generalizable to the larger population.

Suicidal ideation following ketamine prescription in patients with recurrent major depressive disorder: a nation-wide cohort study

Ketamine has gained attention for its effective treatment for patients with major depressive disorder (MDD) and suicidal ideation; Despite numerous studies presenting the rapid efficacy, long-term benefit in real-world populations remains poorly characterized. This is a retrospective cohort study using TriNetX US Collaborative Network, a platform aggregating electronic health records (EHRs) data from 108 million patients from 62 health care organizations in the US, and the study population includes 514,988 patients with a diagnosis of recurrent MDD who were prescribed relevant treatment in their EHRs. The prescription of ketamine was associated with significantly decreased risk of suicidal ideation compared to the prescription of other common antidepressants: HR = 0.63 (95% CI: 0.53–0.76) at 1 day – 7 days, 0.67 (95% CI: 0.59–0.77) at 1 day – 30 days, 0.69 (95% CI: 0.62–0.77) at 1 day – 90 days, 0.74 (95% CI: 0.67–0.81) at 1 day – 180 days, and 0.78 (95% CI: 0.69–0.83) at 1 day – 270 days. This trend was especially robust among adults over 24 years of age, females, males, and White patients with recurrent MDD. This study provides real-world evidence that ketamine has long-term benefits in mitigating suicidal ideation in patients with recurrent MDD. Future work should focus on optimizing dosage regimens for ketamine, understanding the mechanism, and the difference in various demographic subpopulations.

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

Safety and effectiveness of vortioxetine in patients with major depressive disorder in a real-life clinical setting in India: results from an interventional, flexible-dose study

Objective Vortioxetine has demonstrated safety and efficacy in improving symptoms of major depressive disorder (MDD), including overall functioning in real-world settings. This is the first study in a real-life clinical setting in India to evaluate effectiveness and safety of vortioxetine in patients with MDD. Methods This interventional, open-label study consisted of a 12-week treatment period with flexible doses of vortioxetine (5–20 mg/day) in adult patients (aged 18–65 years) with a confirmed MDD diagnosis. Effectiveness outcomes included change from baseline to week 12 in Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression–Severity (CGI-S) scores, along with CGI-Improvement (CGI-I) scores at week 12, using a mixed model for repeated measures. Adverse events (AEs) were recorded for safety outcome assessments. Results Of 395 patients who received vortioxetine, 42.3% were women mean age 38.9 years; 322 patients completed the study. Significant improvement in depressive symptoms was observed in change from baseline to week 12 least squares (LS) mean (SE) PHQ-9 total score (−9.36 [0.276]; p<.0001) and CGI-S score (−2.14 [0.065]; p<.0001). LS mean (SE) CGI-I score showed significant improvement at week 12 (1.93 [0.067]; p<.0001). Subgroup analysis across age, sex, disease severity, and body mass index showed significant improvements in depression symptoms and severity. A total of 35.4% (n = 140) of patients experienced treatment-emergent AEs (mostly mild-moderate); nausea and pruritus were the most frequent (6.6%, n = 26 each). Conclusion Safety and effectiveness of vortioxetine in improving symptoms of MDD over a 12-week period was demonstrated in a real-life clinical setting in India. Clinical trial registration information Open-label, flexible-dose study of vortioxetine in patients with major depressive disorder in India; Clinical Trials.gov ID: NCT04288895; https://www.clinicaltrials.gov/study/NCT04288895

Racial disparities in prosthesis abandonment and mobility outcomes after lower limb amputation from a dysvascular etiology in a veteran population.

Non-Hispanic Black (NHB) individuals have higher rates of amputation and increased risk of a transfemoral amputation due to dysvascular disease than non-Hispanic White (NHW) individuals. However, it is unclear if NHB individuals have differences in prosthesis use or functional outcomes following an amputation. To determine if there are racial disparities in prosthesis abandonment and mobility outcomes in veterans who have undergone their first major unilateral lower extremity amputation (LEA) due to diabetes and/or peripheral artery disease. National cohort study that identified individuals retrospectively through the Veterans Affairs (VA) Corporate Data Warehouse (CDW) from March 1, 2018, to November 30, 2020, then prospectively collected their self-reported prosthesis abandonment and mobility. Multiple logistic regression was used to control for potential confounders and identify potential effect modifiers. The VA CDW, participant mailings and phone calls. Three hundred fifty-seven individuals who underwent an incident transtibial or transfemoral amputation due to diabetes and/or peripheral arterial disease. Not applicable. (1) Self-reported prosthesis abandonment. (2) Level of mobility assessed using the Locomotor Capabilities Index. Rurally located NHB individuals without a major depressive disorder (MDD) had increased odds of abandoning their prosthesis (adjusted odds ratios [aOR] = 5.3; 95% confidence interval [CI]: [1.3-21.1]). This disparity was nearly three times as large for rurally located NHB individuals with MDD diagnosis, compared with other races from rural areas and with MDD (aOR = 15.8; 95% CI, 2.5-97.6). NHB individuals living in an urban area were significantly less likely to achieve advanced mobility, both with MDD (aOR=0.16; 95% CI: [0.04-7.0]) and without MDD (aOR = 0.26; 95% CI: [0.09-0.73]). This study demonstrated that health care disparities persist for NHB veterans following a dysvascular LEA, with increased prosthesis abandonment and worse mobility outcomes.

The role of social determinants of health in mental health: An examination of the moderating effects of race, ethnicity, and gender on depression through the all of us research program dataset

We investigate how select identity characteristics moderate the role of several SDoH domains on major depressive disorder (MDD). Our study considers an analytical sample of 86,954 participants from the NIH-funded All of Us (AoU) Research Program in the USA. Our independent variables and moderators come from survey responses and our outcome is an EHR diagnostic code. We include race/ethnicity and gender/sexual identity to moderate the role of food insecurity, discrimination, neighborhood social cohesion, and loneliness in assessing risk for MDD diagnosis. We examine those moderating effects based on connections seen in the literature. Our findings illustrate the complexity of where and how people live their lives can have significant differential impact on MDD. Women (AOR = 1.60, 95% CI = [1.53, 1.68]) and LGBTQIA2+ individuals (AOR = 1.71, 95% CI = [1.60, 1.84]) exhibit a significantly higher likelihood of MDD diagnosis compared to cisgender heterosexual males. Our study also reveals a lower likelihood of MDD diagnosis among Asian/Asian American individuals (AOR = 0.41, 95% CI = [0.35, 0.49]) compared to White individuals. Our results align with previous research indicating that higher levels of food insecurity (AOR = 1.30, 95% CI = [1.17, 1.44]) and loneliness (AOR = 6.89, 95% CI = [6.04, 7.87]) are strongly associated with an increased likelihood of MDD. However, we also find that social cohesion (AOR = 0.92, 95% CI = [0.81, 1.05]) does not emerge as a significant predictor, contradicting some literature emphasizing the protective role of neighborhood cohesion. Similarly, our finding that transience (AOR = 0.95, 95% CI = [0.92, 0.98]) reduces the likelihood of MDD diagnosis contradicts conventional wisdom and warrants further exploration. Our study provides a reminder of the substantial challenges for research focused on marginalized community segments and that deliberate sampling plans are needed to examine those most marginalized and underserved.

Uric Acid as a Biomarker for Mood Disorders: A Comparative Study of Blood Uric Acid Levels Correlating With the Symptom Severity and Treatment Response.

Background Bipolar affective disorder (BPAD) and major depressive disorder (MDD) are two mood disorders whose pathophysiology may involve the purinergic system. Elevated uric acid levels, associated with this system, can impact various behaviors in individuals affected by these conditions. In addition to genetic predisposition, blood uric acid levels can be impacted by various factors, including metabolic syndrome, the consumption of psychoactive medications, and other underlying kidney conditions such as gout. Objective The study aims to investigate the relationship between blood uric acid levels and mental health conditions, specifically BPAD subtypes (manic and depressive) and MDD. The study also examines changes in blood uric acid levels following treatment and evaluates the effectiveness of different treatment approaches in reducing uric acid levels. Methodology To be eligible to participate, individuals must have a confirmed diagnosis of BPAD (manic or depressive type) or MDD, according to the International Classification of Diseases (ICD-10). Blood uric acid levels were measured at both baseline and follow-up assessments. Symptoms were assessed weekly using standardized rating scales (Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAM-D)) until treatment response was achieved, which was defined as a 50% reduction in initial scores on both scales. We used ANOVA to examine the differences among the three patient groups and paired sample t-tests to examine the changes in means before and after treatment conditions. Results A significant positive correlation was found between the severity of illness and serum uric acid levels across all three patient groups: those with BPAD-mania, BPAD-depression, and MDD. Notably, patients with BPAD-mania patients had significantly higher serum uric acid levels (5.2±0.9 mg/dL) compared to those with BPAD-depression (4.8±1.0 mg/dL) and MDD (4.0±1.1 mg/dL). After treatment, all patient groups exhibited a decrease in serum uric acid levels. The reduction in serum uric acid levels was pronounced in all patient groups, with decreases of 3.1±0.8 mg/dL in patients with BPAD-mania, 3.1±0.9 mg/dL in those with BPAD-depression, and 3.5±1.1 mg/dL in those with MDD. The study showed that the reduction in serum uric acid levels was significantly correlated with the severity of illness in patients with BPAD-mania, but not in those with BPAD-depression or MDD. Furthermore, the study found that treatment with lithium carbonate, sodium valproate, or carbamazepine was equally effective in reducing serum uric acid levels, regardless of the mood stabilizer used. Conclusion The study supports that dysfunction in the purine system might play a significant role in the development and progression of BPAD, suggesting that this phenomenon is not solely due to chronicity or medication exposure. This study also introduces a fresh perspective on the underlying biological processes that contribute to the development of BPAD and also sheds light on new treatment regimens targeting uric acid reduction in treating patients with bipolar disorder.