Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1β in youth

• Type of Material: Article
• Authors: Margaret Tartter, University of California, Los Angeles; Constance Hammen, University of California, Los Angeles; Julienne E. Bower, University of California, Los Angeles; Patricia Brennan, Emory University; Steven Cole, University of California, Los Angeles
• Language: English
• Date: 2015-01-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Elsevier B.V. or its licensors or contributors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbi.2015.01.003
• Title of Journal or Parent Work: Brain, Behavior, and Immunity
• ISSN: 0889-1591
• Volume: 46
• Start Page: 104
• End Page: 111
• Grant/Funding Information: We are also grateful for the assistance of the UCLA Social Genomics Core Laboratory, which is supported by NIH grant P30 AG017265.; This research was supported by National Institutes of Health (NIH) grant R01 MH52239 to CH, JMN, and PAB; by NIH grant T32 MH017140 to MAT; and by a seed grant from the UCLA Cousins Center for Psychoneuroimmunology to JEB, CH, and SWC.
• Keywords: Polymorphism, Single Nucleotide; Alleles; Female; Adolescent; Adolescent depression; IL6; Genetic Predisposition to Disease; Young Adult; Genotype; Male; TNF; Pro-inflammatory cytokines; Gene-Environment Interaction; Stress, Psychological; Adult; Interpersonal Relations; IL1β; Interleukin-1beta; Promoter Regions, Genetic; Depression; Humans; Interleukin-6; Psychiatric Status Rating Scales; Tumor Necrosis Factor-alpha; Gene–environment interaction
• Research Categories: Psychology, Clinical; Biology, Genetics; Health Sciences, Mental Health

Abstract

Aims: Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1β (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms. Methods: Participants were 444 Australian youth (mean age = 20.12) whose exposure to chronic stress in the past 6. months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping. Results: In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1β, previously associated with higher IL-1β expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes. Conclusion: Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to individual differences in depressive symptomatology following interpersonal stress exposure.