Dataset Information

Bridging Basic and Clinical Research in Early Life Adversity, DNA Methylation, and Major Depressive Disorder.

ABSTRACT: Early life adversity (ELA)- including childhood physical, emotional, and sexual abuse, as well as childhood neglect- is an important predictive factor for negative psychopathology, including Major Depressive Disorder (MDD). ELA can epigenetically regulate key emotional and behavioral systems in ways that can stably persist into adulthood and contribute to the development of MDD and other psychopathology. DNA methylation has been one of the most investigated forms of epigenetic regulation in ELA to MDD pathway. From these studies, genes and sites associated with ELA/MDD have been identified and should be further investigated in order to identify potential avenues for intervention.

SUBMITTER: Brown A

PROVIDER: S-EPMC6448008 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Bridging Basic and Clinical Research in Early Life Adversity, DNA Methylation, and Major Depressive Disorder.

Brown Amanda A Fiori Laura M LM Turecki Gustavo G

Frontiers in genetics 20190322

Early life adversity (ELA)- including childhood physical, emotional, and sexual abuse, as well as childhood neglect- is an important predictive factor for negative psychopathology, including Major Depressive Disorder (MDD). ELA can epigenetically regulate key emotional and behavioral systems in ways that can stably persist into adulthood and contribute to the development of MDD and other psychopathology. DNA methylation has been one of the most investigated forms of epigenetic regulation in ELA ...[more]

PMID: 30984237

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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

Bridging Basic and Clinical Research in Early Life Adversity, DNA Methylation, and Major Depressive Disorder.

Publications

Bridging Basic and Clinical Research in Early Life Adversity, DNA Methylation, and Major Depressive Disorder.

Similar Datasets

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