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

Background: 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. Methods: 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). Results: 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. Limitations: Data are nominally significant and not resistant to correction for multiple testing. Conclusion: 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. (C) 2011 Elsevier B.V. All rights reserved.