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Association between toll-like receptor 4 expression and symptoms of major depressive disorder.

ABSTRACT: BACKGROUND:In our previous study, toll-like receptor 4 (TLR4) mRNA expression level was associated with severity of major depressive disorder (MDD) evaluated with the 17-item Hamilton Depression Rating Scale (HAMD-17). However, there are few studies that have investigated the relationship between symptoms of MDD and changes in TLR4 expression. Therefore, the aim of the present study was to further analyze the association between subscales of HAMD-17 and TLR4. METHODS:Fifty-one patients with MDD (15 male and 36 female) participated in this study. HAMD-17 was used to assess the symptoms of major depression. The mRNA expression levels of TLR4 were examined in parallel with a housekeeping gene, using real-time polymerase chain reaction. A stepwise linear regression forward model was used to evaluate the relationships between items of HAMD-17 and TLR4 expression. RESULTS:Some sickness behavior-associated symptoms, including suicide, somatic symptoms of anxiety, or performance of work and activities, were not associated with TLR4 expression. However, psychological signs of anxiety and loss of weight in HAMD-17 can predict the expression level of TLR4. CONCLUSION:Our results suggest a significant association between anxiety, body weight loss, and TLR4 mRNA levels in patients with MDD. Larger longitudinal studies combining both subjective and objective measures of depression are needed to clarify the link between TLR4 and symptoms of depression.

SUBMITTER: Wu MK

PROVIDER: S-EPMC4525784 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association between toll-like receptor 4 expression and symptoms of major depressive disorder.

Wu Ming-Kung MK Huang Tiao-Lai TL Huang Kai-Wei KW Huang Ya-Ling YL Hung Yi-Yung YY

Neuropsychiatric disease and treatment 20150730

<h4>Background</h4>In our previous study, toll-like receptor 4 (TLR4) mRNA expression level was associated with severity of major depressive disorder (MDD) evaluated with the 17-item Hamilton Depression Rating Scale (HAMD-17). However, there are few studies that have investigated the relationship between symptoms of MDD and changes in TLR4 expression. Therefore, the aim of the present study was to further analyze the association between subscales of HAMD-17 and TLR4.<h4>Methods</h4>Fifty-one pat ...[more]

PMID: 26257523

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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 toll-like receptor 4 expression and symptoms of major depressive disorder.

Publications

Association between toll-like receptor 4 expression and symptoms of major depressive disorder.

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