title: Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1β in youth.
abstract: OBJECTIVE
  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 6months 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychology, University of California, Los Angeles, USA. Electronic address: MTartter@ucla.edu.
authors.forename: Margaret
authors.initials: M
authors.lastname: Tartter
authors.affiliation: Department of Psychology, University of California, Los Angeles, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, USA.
authors.forename: Constance
authors.initials: C
authors.lastname: Hammen
authors.affiliation: Department of Psychology, University of California, Los Angeles, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, USA; Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, USA.
authors.forename: Julienne E
authors.initials: JE
authors.lastname: Bower
authors.affiliation: Department of Psychology, Emory University, Atlanta, GA, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Brennan
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, USA; Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, USA; School of Medicine, University of California, Los Angeles, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Cole
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D003863:Depression / Q000235:genetics* / Q000523:psychology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007398:Interpersonal Relations; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000235:genetics* / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Adolescent depression; Depression; Gene–environment interaction; IL1β; IL6; Pro-inflammatory cytokines; TNF