title: Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and childhood-onset mood disorders.
abstract: OBJECTIVE
  Inflammatory cytokines induce a behavioral syndrome, known as sickness behavior, that strongly resembles symptoms typically seen in depression. This resemblance has led to the theory that an imbalance of inflammatory cytokine activity may be a contributing factor in depressive disorders. Support for this is found in multiple lines of evidence, such as the effects of cytokines on the activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain-derived neurotrophic factor, and hippocampal function, all of which are implicated in the etiology of depression. In addition, associations between inflammatory activity and depressive symptomology have been documented in a number of studies, and the depressogenic effects of cytokine therapy are well known. Accordingly, given that depression has a substantial genetic basis, genes involved in the regulation of inflammatory cytokine activity are strong candidates for involvement in genetic susceptibility to depressive disorders. Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and IL10, as candidates for involvement in childhood-onset mood disorders.
  
  
  METHODS
  In this study of 384 families, each ascertained through a child with depression diagnosed before the age of 15 years, 11 polymorphisms of known or likely functional significance (coding and regulatory variants) were analyzed.
  
  
  RESULTS
  Testing for biased transmission of alleles from parents to their affected offspring, we found no evidence for an association between childhood-onset mood disorders and any of the polymorphisms, either individually or as haplotypes.
  
  
  CONCLUSIONS
  The present study does not support the involvement of the TNF, IL1A, IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to early-onset mood disorders.
authors.affiliation: Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: V L
authors.initials: VL
authors.lastname: Misener
authors.forename: L
authors.initials: L
authors.lastname: Gomez
authors.forename: K G
authors.initials: KG
authors.lastname: Wigg
authors.forename: P
authors.initials: P
authors.lastname: Luca
authors.forename: N
authors.initials: N
authors.lastname: King
authors.forename: E
authors.initials: E
authors.lastname: Kiss
authors.forename: G
authors.initials: G
authors.lastname: Daróczi
authors.forename: K
authors.initials: K
authors.lastname: Kapornai
authors.forename: Z
authors.initials: Z
authors.lastname: Tamas
authors.forename: L
authors.initials: L
authors.lastname: Mayer
authors.forename: J
authors.initials: J
authors.lastname: Gádoros
authors.forename: I
authors.initials: I
authors.lastname: Baji
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: M
authors.initials: M
authors.lastname: Kovacs
authors.forename: A
authors.initials: A
authors.lastname: Vetró
authors.forename: C L
authors.initials: CL
authors.lastname: Barr
mesh_terms: D002648:Child; D016207:Cytokines / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D019964:Mood Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C508584:IL1A protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10