Interplay between pro-inflammatory cytokines, childhood trauma, and executive function in depressed adolescents

J Psychiatr Res. 2019 Jul:114:1-10. doi: 10.1016/j.jpsychires.2019.03.030. Epub 2019 Apr 1.

Abstract

Background: Pro-inflammatory cytokines have been linked to depression, early childhood trauma, and impairment in executive function in adults. Whether these links are present during adolescence, a time when vulnerability to depression is heightened, a point more proximal to childhood trauma, and a critical period of brain development, is not well understood.

Method: Serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) were measured in 70 adolescents aged 12-17, including 40 with a DSM-IV depressive disorder (DEP), a sub-set (n = 22) of whom reported a history of childhood trauma (DEP-T), and 30 healthy controls (HCs). Participants completed performance-based (Parametric Go/No-Go Task) and observer-rated (Behavior Rating Inventory of Executive Function) measures of executive function. Procedures were conducted at a subspecialty clinic (Dec 2015-June 2017).

Results: IL-6 was elevated in DEP and DEP-T adolescents compared to controls (p = .014) and TNF-α was elevated in DEP participants only (p = .040) compared to controls, whereas no group differences were found in IL-1β (p = .829). Additionally, DEP-T participants demonstrated relative deficits in performance-based (p = .044) and observer-rated inhibitory control (p = .049) compared to controls. Across the whole sample, TNF-α was associated with performance-based (r = -0.25, p = .039) and observer-rated (r = 0.32, p = .009) inhibitory control deficits. In subgroup analyses, TNF-α was associated with increased observer-rated inhibitory deficits in DEP, and at the trend level, with reduced inhibitory control performance in DEP-T.

Conclusions: The current results suggest that inflammation may be a marker of disease processes in adolescent depression. Though longitudinal studies are needed, depressed adolescents with childhood trauma exposure appear to constitute a uniquely vulnerable group in terms of objective risk for executive dysfunction. Immune dysregulation may partly contribute to this risk.

Keywords: Adolescence; Depression; Executive function; Inflammation; Trauma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adverse Childhood Experiences*
  • Case-Control Studies
  • Child
  • Cytokines / blood*
  • Depression / blood
  • Depression / etiology
  • Depression / metabolism
  • Depression / psychology*
  • Executive Function*
  • Female
  • Humans
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Male
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha