Early life adversity is associated with differential gene expression in immune cells: A cluster-based analysis across an acute psychosocial stressor

Laura Etzel, Abner T. Apsley, Waylon J. Hastings, Qiaofeng Ye, Idan Shalev

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Elucidating mechanisms by which early-life adversity (ELA) contributes to increased disease risk is important for mitigating adverse health outcomes. Prior work has found differences in immune cell gene expression related to inflammation and mitochondrial activity. Using a within-person between-group experimental design, we investigated differences in gene expression clusters across acute psychosocial stress and no-stress conditions. Participants were young adults (N = 29, aged 18 – 25 years, 62 % female, 47 % with a history of ELA). Gene expression was assessed in peripheral blood mononuclear cells collected at 8 blood draws spanning two 5-hour sessions (stress vs. no-stress) separated by a week, 4 across each session (number of observations = 221). We applied two unsupervised gene clustering methods – latent profile analysis (LPA) and weighted gene co-expression analysis (WGCNA) – to cluster genes with similar expression patterns across participants. LPA identified 11 clusters, 7 of which were significantly associated with ELA-status. WGCNA identified 5 clusters, 3 of which were significantly associated with ELA-status. LPA- and WGCNA-identified clusters were correlated, and all clusters were highly preserved across sessions and time. There was no significant effect of acute stress on cluster gene expression, but there was a significant effect of time, and significant differences by ELA-status. ELA-associated clusters related to RNA splicing/processing, inflammation, leukocyte differentiation and division, and mitochondrial activity were differentially expressed across time: ELA-exposed individuals showed decreased expression of these clusters at 90-minutes while controls showed increased expression. Our findings replicate previous work in this area and highlight additional mechanisms by which ELA may contribute to disease risk.

Original languageEnglish (US)
Pages (from-to)724-733
Number of pages10
JournalBrain, Behavior, and Immunity
StatePublished - Jul 2024

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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