A Meta-Analysis of 5-Hydroxytryptamine Receptor 1B Polymorphisms With Risk of Major Depressive Disorder and Suicidal Behavior.
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SUBMITTER: Yang P
PROVIDER: S-EPMC8311000 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceMajor depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples.ObjectiveTo describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines.Design, setting, and participantsThis population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022.ExposuresPatients with MDD with and without records of suicidal behavior.Main outcomes and measuresThe main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated.ResultsA total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed.Conclusions and relevanceThis cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.
| S-EPMC10433143 | biostudies-literature
Project description:Although an association between major depressive disorder (MDD) and suicide exists, most depressed patients never attempt suicide. An improved understanding of the factors contributing to suicidal risk in MDD can provide direction for suicide predictor development. In MDD suicide attempters (MDD-SA), MDD non-attempters (MDD-NA), and healthy controls (HC) (n = 12 each group), complementary plasma proteomics identified 45 differential proteins mapped to coagulation and inflammation, 25 of which underwent Western blotting. In another cohort including antidepressant-treated patients (n = 49 each group), seven additional extrinsic pathway proteins were selected for ELISA. Two inflammatory proteins and eight coagulatory proteins demonstrated alterations in MDD-SA relative to MDD-NA and HC. Applying a relative mass-action ratio, MDD-SA subjects displayed a higher relative prothrombinase activity than MDD-NA subjects, while healthy controls displayed higher relative prothrombinase activity than both MDD-SA and MDD-NA subjects. Consistent with our human findings, we found that heparin treatment significantly increased forced swimming test (FST) immobility time in rodents. MDD, independent of suicidality, is associated with a proinflammatory state accompanied by a hypothrombotic state. Suicidal behavior in MDD is associated with a more pronounced proinflammatory and prothrombotic phenotype accompanied by extrinsic pathway activation, revealing an extrinsic pathway biomarker that can be applied in predicting and monitoring suicidal risk.
| S-EPMC5015115 | biostudies-literature
Project description:EPIC array data were generated from 2 MDD case control cohorts. EWAS was performed in each cohort, followed by meta-analysis between the 2 cohort. Cohort 1: A total of 191 blood samples from 112 patients with MDD was collected up till the interim analysis (wave 1 samples) from an observational clinical study OBSERVEMDD0001 (ClinicalTrials.gov Identifier: NCT02489305) compared to 32 healthy controls; Cohort 2: The MDD cases (N = 359) were drawn from the Molecular Biomarkers of Antidepressant Response study compared to 68 healthy controls.
2022-11-03 | GSE198904 | GEO
Project description:BackgroundWe sought to evaluate the prevalence and correlates of major depressive disorder (MDD) and suicidal behavior among urban dwelling Ethiopian adults.MethodsThis was a cross-sectional study of 1097 outpatient adults (≥18 years of age) in a major hospital in Addis Ababa, Ethiopia. Sociodemographic and lifestyle characteristics were collected via structured interviews. MDD and suicidal behavior were assessed using the Composite International Diagnostic Interview (CIDI) among all study participants. Multivariable logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI).ResultsPrevalence estimates for lifetime and 12-month MDD were 18.0% and 6.7%, respectively. The prevalence of suicidal behavior during the previous year (i.e., suicidal ideation, plan or attempt) was 15.2% with approximately 4% having reported attempts. Overall, women were more likely to report suicidal behavior (17.8%) than men (11.3%). MDD odds were 1.53-fold higher among women as compared with men (aOR=1.53, 95% CI 1.05-2.23). Lifetime MDD was significantly associated with age, sex, marital status, and self-reported physical health. Participants reporting poor mental health had approximately 3-fold increased odds of MDD (OR=2.93; 95%CI: 1.05-2.23); those between 35 and 44 years old (aOR=1.92; 95%CI: 1.06-3.49) and those older than 55 years (aOR=2.54; 95%CI: 1.16-5.57) had higher odds of MDD. Similarly suicidal behavior was significantly associated with sex, marital status, and self-reported physical and mental health.LimitationsThis cross-sectional study utilized self-reported data from outpatients. Causality cannot be inferred, and results may not be fully generalizable.ConclusionsOverall results show that MDD and suicidal behavior are highly prevalent among urban-dwelling Ethiopian adults. Women and middle-age adults constitute a high-risk group and may therefore benefit from targeted interventions.
| S-EPMC4964269 | biostudies-literature
Project description:BackgroundThe impact of treatment-resistant depression (TRD) or prior suicidal ideation/suicide attempt (SI/SA) on mortality by suicide among patients with major depressive disorder (MDD) is not well known. This retrospective, observational, descriptive cohort study characterized real-world rates of suicide-specific mortality among patients with MDD with or without TRD or SI/SA.MethodsAdult patients with MDD among commercially insured and Medicare enrollees in Optum Research Database were included and assigned to three cohorts: those with treatment-resistant MDD (TRD), those with MDD and SI/SA (MDD+SI/SA), and those with MDD without TRD or SI/SA (MDD alone). Suicide-specific mortality was obtained from the National Death Index. The effects of demographic characteristics and SI/SA in the year prior to the end of observation on suicide-specific mortality were assessed.ResultsFor the 139,753 TRD, 85,602 MDD+SI/SA, and 572,098 MDD alone cohort patients, mean age ranged from 55 to 59 years and the majority were female. At baseline, anxiety disorders were present in 53.92%, 44.11%, and 21.72% of patients with TRD, MDD+SI/SA, and MDD alone, respectively. Suicide-mortality rates in the three cohorts were 0.14/100 person-years for TRD, 0.27/100 person-years for MDD+SI/SA, and 0.04/100 person-years for MDD alone. SI/SA during the year prior to the end of observation, younger age, and male sex were associated with increased suicide risk.ConclusionsPatients with TRD and MDD+SI/SA have a heightened risk of mortality by suicide compared with patients with MDD alone. Suicide rates were higher in patients with recent history versus older or no history of SI/SA, men versus women, and those of young age versus older age.
| S-EPMC10454258 | biostudies-literature
Project description:Purpose/backgroundNumerous health authority approvals of esketamine nasal spray, combined with oral antidepressant, to treat depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior were based on 2 identically designed, double-blind, phase 3 studies.Methods/proceduresAcross both ASPIRE studies (NCT03039192, NCT03097133), patients (N = 456) were randomized to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks plus comprehensive standard of care, including hospitalization and newly initiated or optimized antidepressant(s). In post hoc analyses of pooled data, changes from baseline at 24 hours after the first dose in Montgomery-Åsberg Depression Rating Scale total score and Clinical Global Impression-Severity of Suicidality-Revised, in the full cohort and in subgroups, were analyzed using analysis of covariance.Findings/resultsEsketamine plus standard of care demonstrated significantly greater improvement in Montgomery-Åsberg Depression Rating Scale total score versus placebo plus standard of care at 24 hours (least square mean difference [95% confidence interval], -3.8 [-5.75 to -1.89]) and at earlier (4 hours: -3.4 [-5.05 to -1.71]) and later time points (day 25: -3.4 [-5.36 to -1.36]). The between-group difference (95% confidence interval) for change in Clinical Global Impression-Severity of Suicidality-Revised at 24 hours was -0.20 (-0.43 to 0.04) for all patients and -0.31 (-0.61 to -0.01) for those with a history of suicide attempt. Common adverse events (≥20%) during esketamine treatment were dizziness, dissociation, nausea, somnolence, and headache.Implications/conclusionsEsketamine plus comprehensive standard of care rapidly reduces depressive symptoms in patients with major depressive disorder who have acute suicidal ideation or behavior, especially in those with a history of suicide attempt, providing a new treatment option for this particularly ill and vulnerable population.
| S-EPMC8407443 | biostudies-literature
Project description:Magnetization transfer imaging (MTI) provides a quantitative measure of the macromolecular structural integrity of brain tissue, as represented by magnetization transfer ratio (MTR). In this study, we utilized MTI to identify biophysical alterations in MDD patients with a history of suicide attempts relative to MDD patients without such history. The participants were 36 medication-free MDD patients, with (N = 17) and without (N = 19) a history of a suicide attempt, and 28 healthy controls matched for age and gender. Whole brain voxel-based analysis was used to compare MTR across three groups and to analyze correlations with symptom severity and illness duration. We identified decreased MTR in left inferior parietal lobule and right superior parietal lobule in suicide attempters relative to both non-attempters and controls. Non-attempters also showed significantly reduced MTR in left inferior parietal lobule relative to controls, as well as an MTR reduction in left cerebellum. These abnormalities were not correlated with symptom severity or illness duration. Depressed patients with a history of suicide attempt showed bilateral abnormalities in parietal cortex compared to nonsuicidal depressed patients and healthy controls. Parietal lobe abnormalities might cause attentional dysfunction and impaired decision making to increase risk for suicidal behavior in MDD.
| S-EPMC4389668 | biostudies-literature
Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.
2011-10-04 | E-GEOD-19738 | biostudies-arrayexpress
Project description:This study explored the impact of social support on suicidal ideation in 169 prisoners with major depressive disorder, accounting for known demographic, criminological, and clinical risk factors. Greater social support was associated with a lower likelihood of the presence of current suicide ideation. This effect remained significant even after adjusting for other significant predictors of suicide ideation including sex, length of sentence served, severity of current depression, and having prior suicide attempts. This study is the first to explore social support and other known risk factors for suicide ideation in a prison population with major depressive disorder. Our findings demonstrate that, even in the presence of significant risk factors for suicidal ideation, social support remained a strong predictor, suggesting the importance of fostering social support in correctional settings.
| S-EPMC7067664 | biostudies-literature
Project description:Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SI n = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22-42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80-1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management.
| S-EPMC10721812 | biostudies-literature