Early-life adversity severity, timing, and context type are associated with SLC6A4 methylation in emerging adults: Results from a prospective cohort study.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Pergamon Press Country of Publication: England NLM ID: 7612148 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3360 (Electronic) Linking ISSN: 03064530 NLM ISO Abbreviation: Psychoneuroendocrinology Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford, Elmsford, N. Y., Pergamon Press.
    • Subject Terms:
      Serotonin Plasma Membrane Transport Proteins*/genetics ; Adverse Childhood Experiences* ; DNA Methylation*/genetics ; CpG Islands*/genetics ; Epigenesis, Genetic*/genetics; Humans ; Female ; Male ; Prospective Studies ; Adolescent ; Young Adult ; Adult ; Stress, Psychological/genetics ; Stress, Psychological/metabolism ; Promoter Regions, Genetic/genetics ; Child
    • Abstract:
      Background: Epigenetic modifications, including DNA methylation (DNAm), can play a role in the biological embedding of early-life adversity (ELA) through serotonergic mechanisms. The current study examines methylation of the CpG island in the promoter region of the stress-responsive serotonin transporter gene (SLC6A4) and is the first to jointly assess how it is influenced by ELA severity, timing, and type-specifically, deprivation and threat.
      Methods: We use data from 627 Youth Emotion Project study participants, recruited from two US high schools. Using adjusted linear regressions, we analyze DNA collected in early adulthood from 410 participants and ELA based on interviewer-rated responses from concurrent Childhood Trauma Interviews, adjusting for survey-measured covariates.
      Results: ELA robustly predicted mean CpG island SLC6A4 DNAm percent across 71 CpG sites. Each additional major-severity ELA event was associated with a 0.121-percentage-point increase (p<0.001), equating to a 0.177 standard deviation (sd) higher DNAm level (95 % CI: 0.080, 0.274) with each 1-sd higher adversity score. When modeled separately, both childhood and adolescent ELA predicted SLC6A4 DNAm. When modeled jointly, adolescent ELA was most strongly predictive, and child adversity remained significantly associated with DNAm through indirect associations via adolescent adversity. Additionally, the ELA-SLC6A4 DNAm association may vary by adversity type. Across separate models for childhood and adolescent exposures, deprivation coefficients are positive and statistically significant. Meanwhile, threat coefficients are positive and not significantly significant but do not statistically differ from deprivation coefficients. In models including all ELA dimensions, one major adolescent deprivation event is associated with a 0.222-percentage-point increased SLC6A4 DNAm (p<0.05), or a 1-sd higher deprivation score with a 0.157-sd increased DNAm.
      Conclusion: Results further implicate epigenetic modification on serotonergic neurotransmission via DNAm in the downstream sequelae of ELA-particularly adolescent deprivation-and support preventive interventions in adolescence to mitigate biological embedding.
      Competing Interests: Declaration of Competing Interest None.
      (Copyright © 2024. Published by Elsevier Ltd.)
    • Contributed Indexing:
      Keywords: DNA methylation; Deprivation; Early life adversity; Epigenetics; Threat; Youths
    • Accession Number:
      0 (Serotonin Plasma Membrane Transport Proteins)
      0 (SLC6A4 protein, human)
    • Publication Date:
      Date Created: 20240919 Date Completed: 20241003 Latest Revision: 20241009
    • Publication Date:
      20241009
    • Accession Number:
      10.1016/j.psyneuen.2024.107181
    • Accession Number:
      39298801