Bridging Basic and Clinical Research in Early Life Adversity, DNA Methylation, and Major Depressive Disorder.
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ABSTRACT:
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]
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Project description:Social anxiety disorder (SAD) is a psychiatric disorder characterized by extensive fear in social situations. Multiple genetic and environmental factors are known to contribute to its pathogenesis. One of the main environmental risk factors is early life adversity (ELA). Evidence is emerging that epigenetic mechanisms such as DNA methylation might play an important role in the biological mechanisms underlying SAD and ELA. To investigate the relationship between ELA, DNA methylation, and SAD, we performed an epigenome-wide association study for SAD and ELA examining DNA from whole blood of a cohort of 143 individuals using DNA methylation arrays. We identified two differentially methylated regions (DMRs) associated with SAD located within the genes SLC43A2 and TNXB. As this was the first epigenome-wide association study for SAD, it is worth noting that both genes have previously been associated with panic disorder. Further, we identified two DMRs associated with ELA within the SLC17A3 promoter region and the SIAH3 gene and several DMRs that were associated with the interaction of SAD and ELA. Of these, the regions within C2CD2L and MRPL28 showed the largest difference in DNA methylation. Lastly, we found that two DMRs were associated with both the severity of social anxiety and ELA, however, neither of them was found to mediate the contribution of ELA to SAD later in life. Future studies are needed to replicate our findings in independent cohorts and to investigate the biological pathways underlying these effects.
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