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Impact of Expression and Genetic Variation of microRNA-34b/c on Cognitive Dysfunction in Patients with Major Depressive Disorder.

ABSTRACT: Background:Patients suffering from major depressive disorder (MDD) commonly demonstrate lower performance across multiple cognitive domains. Cognitive impairment is an intrinsic characteristic of MDD status and is often influenced by genetic factors. microRNAs (miRNAs or miRs) have been shown to have important implications in the etiology of MDD. Therefore, we aimed to identify and analyze the impact of expression and genetic variation of miR-34b/c on cognitive dysfunction in MDD. Methods:First, we analyzed miR-34c-5p expression in 48 cases of MDD and 54 healthy controls in a Chinese population using qRT-PCR. We assessed the relationship between the level of miR-34c-5p expression and cognitive performance by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test (TMT). Second, in order to characterize allelic effects of miR-34b/c on cognitive performance in MDD patients, we performed genetic association analysis of single-nucleotide polymorphism (SNP) loci of the MIR34B/C genes with cognitive function in a second group consisting of 531 MDD patients and 267 healthy controls. Results:We found a significant negative correlation between the level of miR-34c-5p expression and both the language and delayed memory index scores in patients with MDD. We also found a significant positive correlation between the level of miR-34c-5p expression and the time required to complete tests A and B of the TMT. The interaction between the rs2187473 genotype and the disease was significant for both immediate memory and delayed memory. In the patient group, the rs2187473 CC genotype was significantly associated with higher performance on immediate memory (F = 6.683, p < 0.05) and delayed memory tasks (F = 4.221, p < 0.05). Conclusion:Our findings suggest that changes in miR-34c expression level have important impacts on cognitive function in patients with MDD. In particular, the polymorphism rs2187473 is a potential genetic risk factor for cognitive function in MDD, which may be of clinical use.

SUBMITTER: Sun N

PROVIDER: S-EPMC7311205 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Impact of Expression and Genetic Variation of microRNA-34b/c on Cognitive Dysfunction in Patients with Major Depressive Disorder.

Sun Ning N Yang Chunxia C He Xiaoting X Liu Zhifen Z Liu Sha S Li Xinrong X Wang Yanfang Y Jin Ruihua R Zhang Kerang K

Neuropsychiatric disease and treatment 20200619

<h4>Background</h4>Patients suffering from major depressive disorder (MDD) commonly demonstrate lower performance across multiple cognitive domains. Cognitive impairment is an intrinsic characteristic of MDD status and is often influenced by genetic factors. microRNAs (miRNAs or miRs) have been shown to have important implications in the etiology of MDD. Therefore, we aimed to identify and analyze the impact of expression and genetic variation of miR-34b/c on cognitive dysfunction in MDD.<h4>Met ...[more]

PMID: 32606706

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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

Impact of Expression and Genetic Variation of microRNA-34b/c on Cognitive Dysfunction in Patients with Major Depressive Disorder.

Publications

Impact of Expression and Genetic Variation of microRNA-34b/c on Cognitive Dysfunction in Patients with Major Depressive Disorder.

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