Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events

Abstract

Depression is accompanied by an inflammatory reaction and activation of cell mediated immunity (CMI) and stressors may induce the cytokine network in humans. The proinflammatory cytokine interleukin-18 (IL-18) is less investigated in depression but highly relevant since it is produced by activated macrophages and expressed in the brain. The distribution of six polymorphisms in IL10, IL18 and NF was compared between patients with a single episode of depression either preceded by a stressful life event (n=182), or occurring without a prior stressful life event (n=106) and a group of healthy control individuals (n=335). The major C allele of the IL18 rs187238 and the major G allele of rs1946518 had a significantly higher prevalence among the patients with a stressful life event prior to onset of disease than both patients without a stressful life event and compared with the healthy controls individuals. None of the examined IL10 or NF alleles were differently distributed among these groups. Data are nominally significant and not resistant to correction for multiple testing. The major C allele of the IL18 rs187238 and the major G allele rs1946518 have previously been associated with higher expression of IL-18 mRNA. Our data suggest that this genetic trend towards higher IL-18 production may increase the susceptibility to depression in response to stressful life events.