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DNA methylation differences associated with social anxiety disorder and early life adversity.

ABSTRACT: 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.

SUBMITTER: Wiegand A

PROVIDER: S-EPMC7862482 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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DNA methylation differences associated with social anxiety disorder and early life adversity.

Wiegand Ariane A Kreifelts Benjamin B Munk Matthias H J MHJ Geiselhart Nadja N Ramadori Katia E KE MacIsaac Julia L JL Fallgatter Andreas J AJ Kobor Michael S MS Nieratschker Vanessa V

Translational psychiatry 20210204 1

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 ...[more]

PMID: 33542190

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Project description:BackgroundSocial anxiety disorder is characterized by intense fear and avoidance of social interactions and scrutiny by others. Although alterations in attentional control seem to play a central role in the psychopathology of social anxiety disorder, the neural underpinnings in prefrontal brain regions have not yet been fully clarified.MethodsThe present study used functional MRI in participants (age 18-50 yr) with social anxiety disorder (n = 42, 31 female) and without (n = 58, 33 female). It investigated the interrelation of the effects of social anxiety disorder and early-life adversity (a main environmental risk factor of social anxiety disorder) on brain activity during an attentional control task. We applied DNA methylation analysis to determine whether epigenetic modulation in the gene encoding the glucocorticoid receptor, NR3C1, might play a mediating role in this process.ResultsWe identified 2 brain regions in the left and medial prefrontal cortex that exhibited an interaction effect of social anxiety disorder and early-life adversity. In participants with low levels of early-life adversity, neural activity in response to disorder-related stimuli was increased in association with social anxiety disorder. In participants with high levels of early-life adversity, neural activity was increased only in participants without social anxiety disorder. NR3C1 DNA methylation partly mediated the effect of social anxiety disorder on brain activity as a function of early-life adversity.LimitationsThe absence of behavioural correlates associated with social anxiety disorder limited functional interpretation of the results.ConclusionThese findings demonstrate that the neurobiological processes that underlie social anxiety disorder might be fundamentally different depending on experiences of early-life adversity. Long-lasting effects of early-life adversity might be encoded in NR3C1 DNA methylation and entail alterations in social anxiety disorder-related activity patterns in the neural network of attentional control.

Dataset Information

DNA methylation differences associated with social anxiety disorder and early life adversity.

Publications

DNA methylation differences associated with social anxiety disorder and early life adversity.

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