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Acute stress induces changes in epigenome-wide DNA methylation.

Lea Zillich1, Nathaly S Czernin1, Oscar Crespo Salvador1

  • 1Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
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Acute stress dynamically alters DNA methylation (DNAm) patterns, influencing cortisol reactivity and implicating genes in thyroid function and cognition. This study reveals dynamic epigenetic changes following stress exposure.

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Area of Science:

  • Neuroscience
  • Epigenetics
  • Endocrinology

Background:

  • Stress significantly impacts mental and somatic health by disrupting the hypothalamic-pituitary-adrenal (HPA) axis.
  • Epigenetic mechanisms, especially DNA methylation (DNAm), are hypothesized to mediate the link between stress and health outcomes.
  • The longitudinal effects of acute stress on DNAm remain largely unexplored.

Purpose of the Study:

  • To investigate the relationship between acute stress, cortisol reactivity, and dynamic changes in DNA methylation.
  • To identify specific DNA methylation patterns and genes associated with stress response.

Main Methods:

  • 122 healthy individuals underwent the Maastricht Acute Stress Test (MAST).
  • Salivary cortisol was measured at seven time points; blood was collected for DNA methylation analysis pre- and post-stress.
  • Statistical analyses included robust linear models for cortisol reactivity prediction and mixed linear models for longitudinal DNAm changes.

Main Results:

  • Baseline DNA methylation predicted cortisol reactivity, with 120 CpG sites and four differentially methylated regions (DMRs) identified.
  • Longitudinal epigenome-wide analysis revealed dynamic DNAm changes at 32 CpG sites and four DMRs post-stress.
  • Gene Ontology analysis highlighted terms related to learning, cognition, and synaptic processes, with TTR and TSHR genes identified as key hits.

Conclusions:

  • Acute stress is associated with dynamic changes in DNA methylation, which are linked to cortisol reactivity.
  • Key genes involved in thyroid function and transcriptional regulation are implicated in the acute stress response.
  • Further multi-omics research is needed to validate these findings and explore their functional significance.