Dataset Information

Association between serum lipid concentrations and attempted suicide in patients with major depressive disorder: A meta-analysis.

ABSTRACT: Background: There is growing evidence that serum lipid concentrations may be associated with attempted suicide in patients with major depressive disorder (MDD), but these findings remain controversial. Thus, we performed a comprehensive meta-analysis to quantitatively assess the associations between serum lipid concentrations and attempted suicide in MDD patients.

Materials and methods: Electronic databases (PubMed, Embase, the Cochrane Library and the China National Knowledge Library) were searched for relevant literature up to 10 February 2020. We used a random-effects model based on heterogeneity amongst studies and generated pooled standardised mean differences (SMDs).

Results: Thirty-two studies comprising 7,068 subjects met the inclusion criteria. A pooled analysis showed that compared with non-attempters, MDD patients who had attempted suicide had significantly lower serum concentrations of total cholesterol (TC) (SMD: -0.63, 95% CI: -0.83 to -0.44) and low-density lipoprotein cholesterol (LDL-C) (SMD: -0.69, 95% CI: -1.04 to -0.34), but the serum concentrations of high-density lipoprotein cholesterol (HDL-C) (SMD: -0.12, 95% CI: -0.33 to 0.10) and triglycerides (TGs) (SMD: 0.00, 95% CI: -0.20 to 0.20) were not significantly different between the two groups. Subgroup and meta-regression analysis indicated that heterogeneity with respect to TC concentrations may be due to different ages (p = 0.041) and sample sizes (p = 0.016) of studies, and that heterogeneity with respect to HDL-C concentrations may be partly due to different settings of studies (p = 0.017).

Conclusions: This meta-analysis demonstrated that lower concentrations of TC and LDL-C, but not of HDL-C and TGs, were associated with attempted suicide in MDD patients. This indicates that TC and LDL-C may be useful as biological markers for predicting whether MDD patients may attempt to commit suicide.

SUBMITTER: Li H

PROVIDER: S-EPMC7728216 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association between serum lipid concentrations and attempted suicide in patients with major depressive disorder: A meta-analysis.

Li Huan H Zhang Xueyan X Sun Qing Q Zou Rui R Li Zhijun Z Liu Shengyuan S

PloS one 20201210 12

<h4>Background</h4>There is growing evidence that serum lipid concentrations may be associated with attempted suicide in patients with major depressive disorder (MDD), but these findings remain controversial. Thus, we performed a comprehensive meta-analysis to quantitatively assess the associations between serum lipid concentrations and attempted suicide in MDD patients.<h4>Materials and methods</h4>Electronic databases (PubMed, Embase, the Cochrane Library and the China National Knowledge Libra ...[more]

PMID: 33301469

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Project description:Background: Individuals with major depressive disorder (MDD) and a lifetime history of attempted suicide demonstrate lower antidepressant response rates than those without a prior suicide attempt. Identifying biomarkers of antidepressant response and lifetime history of attempted suicide may help augment pharmacotherapy selection and improve the objectivity of suicide risk assessments. Towards this goal, this study sought to use network science approaches to establish a multi-omics (genomic and metabolomic) signature of antidepressant response and lifetime history of attempted suicide in adults with MDD. Methods: Single nucleotide variants (SNVs) which associated with suicide attempt(s) in the literature were identified and then integrated with a) p180-assayed metabolites collected prior to antidepressant pharmacotherapy and b) a binary measure of antidepressant response at 8 weeks of treatment using penalized regression-based networks in 245 'Pharmacogenomics Research Network Antidepressant Medication Study (PGRN-AMPS)' and 103 'Combining Medications to Enhance Depression Outcomes (CO-MED)' patients with major depressive disorder. This approach enabled characterization and comparison of biological profiles and associated antidepressant treatment outcomes of those with (N = 46) and without (N = 302) a self-reported lifetime history of suicide attempt. Results: 351 SNVs were associated with suicide attempt(s) in the literature. Intronic SNVs in the circadian genes CLOCK and ARNTL (encoding the CLOCK:BMAL1 heterodimer) were amongst the top network analysis features to differentiate patients with and without a prior suicide attempt. CLOCK and ARNTL differed in their correlations with plasma phosphatidylcholines, kynurenine, amino acids, and carnitines between groups. CLOCK and ARNTL-associated phosphatidylcholines showed a positive correlation with antidepressant response in individuals without a prior suicide attempt which was not observed in the group with a prior suicide attempt. Conclusion: Results provide evidence for a disturbance between CLOCK:BMAL1 circadian processes and circulating phosphatidylcholines, kynurenine, amino acids, and carnitines in individuals with MDD who have attempted suicide. This disturbance may provide mechanistic insights for differential antidepressant pharmacotherapy outcomes between patients with MDD with versus without a lifetime history of attempted suicide. Future investigations of CLOCK:BMAL1 metabolic regulation in the context of suicide attempts may help move towards biologically-augmented pharmacotherapy selection and stratification of suicide risk for subgroups of patients with MDD and a lifetime history of attempted suicide.

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.

Dataset Information

Association between serum lipid concentrations and attempted suicide in patients with major depressive disorder: A meta-analysis.

Publications

Association between serum lipid concentrations and attempted suicide in patients with major depressive disorder: A meta-analysis.

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