title: Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events.
abstract: 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.
  
  
  CONCLUSIONS
  Data are nominally significant and not resistant to correction for multiple testing.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Immunology, the Blood Bank, the National University Hospital, Copenhagen, Denmark. Electronic address: ehaastrup@hotmail.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Haastrup
authors.affiliation: Psychiatric Centre, National University Hospital, Copenhagen, Denmark.
authors.forename: Jens Drachmann
authors.initials: JD
authors.lastname: Bukh
authors.affiliation: Psychiatric Centre, National University Hospital, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Bock
authors.affiliation: Psychiatric Centre, National University Hospital, Copenhagen, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: Department of Clinical Immunology, the Blood Bank, the National University Hospital, Copenhagen, Denmark.
authors.forename: Lise Wegner
authors.initials: LW
authors.lastname: Thørner
authors.affiliation: Research Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Research Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.affiliation: Psychiatric Centre, National University Hospital, Copenhagen, Denmark.
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: Department of Clinical Immunology, the Blood Bank, the National University Hospital, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003863:Depression / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics*; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013315:Stress, Psychological / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10