A Functional Interleukin-18 Haplotype Predicts Depression and Anxiety through Increased Threat-Related Amygdala Reactivity in Women but Not Men.

Journal Article (Journal Article)

Common functional polymorphisms in the gene encoding interleukin-18 (IL18), a cytokine belonging to the IL-1 superfamily that can induce synthesis of several other cytokines, have been associated with major depressive episodes following the experience of stressful life events. The neural mechanisms underlying these associations remain unexamined. Here we use an imaging genetics strategy to examine the effects of risk-related IL18 haplotypes comprising rs187238 and rs1946518 on threat-related amygdala reactivity and, through an indirect effect, stress-related symptoms of depression and anxiety in 448 non-Hispanic Caucasian university students. Analyses indicated that women but not men possessing an IL18 haplotype comprising both risk-related alleles evidenced increased threat-related left centromedial amygdala reactivity relative to other haplotype groups. Moreover, in women only, increased threat-related left centromedial amygdala reactivity predicted increased symptoms of depression and anxiety in individuals also reporting higher levels of life stress. Path analyses revealed a significant indirect effect of IL18 risk haplotype on symptoms of depression and anxiety through increased threat-related amygdala reactivity. These results suggest that a common functional IL18 haplotype associated with heightened proinflammatory responses confers susceptibility to stress-related depression and anxiety through effects on threat-related amygdala function, a risk pathway specific to women. If replicated, these patterns can inform the search for personalized interventions targeting neurobiological pathways of risk associated with inflammation.

Full Text

Duke Authors

Cited Authors

  • Swartz, JR; Prather, AA; Di Iorio, CR; Bogdan, R; Hariri, AR

Published Date

  • January 2017

Published In

Volume / Issue

  • 42 / 2

Start / End Page

  • 419 - 426

PubMed ID

  • 27430614

Pubmed Central ID

  • PMC5399226

Electronic International Standard Serial Number (EISSN)

  • 1740-634X

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/npp.2016.129


  • eng