Cumulative Risk on Oxytocin-Pathway Genes Impairs Default Mode Network Connectivity in Trauma-Exposed Youth

Maor Zeev-Wolf, Jonathan Levy, Richard P. Ebstein, Ruth Feldman*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)
51 Downloads (Pure)

Abstract

Background: Although the default mode network (DMN) is a core network essential for brain functioning, little is known about its developmental trajectory, particularly on factors associated with its coherence into a functional network. In light of adult studies indicating DMN's susceptibility to stress-related conditions, we examined links between variability on oxytocin-pathway genes and DMN connectivity in youth exposed to chronic war-related trauma

Methods: Following a cohort of war-exposed children from early childhood, we imaged the brains of 74 preadolescents (age 11-13 years; 39 war-exposed) during rest using magnetoencephalography (MEG). A cumulative risk index on oxytocin-pathway genes was constructed by combining single nucleotide polymorphisms on five genes previously linked with social deficits and psychopathology; OXTR rs1042778, OXTR rs2254298, OXTRrs53576, CD38 rs3796863, and AVPR1A RS3. Avoidant response to trauma reminders in early childhood and anxiety disorders in late childhood were assessed as predictors of disruptions to DMN theta connectivity.

Results: Higher vulnerability on oxytocin-pathway genes predicted greater disruptions to DMN theta connectivity. Avoidant symptoms in early childhood and generalized anxiety disorder in later childhood were related to impaired DMN connectivity. In combination, stress exposure, oxytocin-pathway genes, and stress-related symptoms explained 24.6% of the variance in DMN connectivity, highlighting the significant effect of stress on the maturing brain.

Conclusions: Findings are the first to link the oxytocin system and maturation of the DMN, a core system sustaining autobiographical memories, alteration of intrinsic and extrinsic attention, mentalization, and sense of self. Results suggest that oxytocin may buffer the effects of chronic early stress on the DMN, particularly theta rhythms that typify the developing brain.

Original languageEnglish
Article number335
Number of pages13
JournalFrontiers in Endocrinology
Volume11
DOIs
Publication statusPublished - 22 May 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • OXTR
  • magnetoencephalography
  • trauma exposure
  • anxiety disorders
  • longitudinal studies
  • genetics
  • POSTTRAUMATIC-STRESS-DISORDER
  • STATE FUNCTIONAL CONNECTIVITY
  • RECEPTOR GENE
  • MATERNAL DEPRESSION
  • SOCIAL ENGAGEMENT
  • BRAIN OXYTOCIN
  • YOUNG-CHILDREN
  • MENTAL-HEALTH
  • OXTR GENE
  • ASSOCIATION

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