title: Cross-species evidence for the role of interleukin-33 in depression risk.
abstract: Extensive evidence highlights the role of inflammatory processes in major depressive disorder (MDD). However, most studies have examined a consistent set of inflammatory cytokines and there is evidence that other immune-derived products may play a role in MDD. In this article, we present data from 3 complimentary studies that support the role of a novel cytokine, interleukin-33 (IL-33), in depression risk. First, we show that a 2-SNP haplotype in the IL-33 gene (rs11792633 and rs7044343) moderated the link between women's history of childhood abuse and their history of recurrent MDD (rMDD), such that the link between childhood abuse and rMDD was stronger among women with fewer copies of the protective IL-33 CT haplotype. Second, linking these findings to differences in circulating cytokine levels, we show in a separate sample that those with a history of rMDD had higher peripheral levels of IL-33 and IL-1β compared with women with a single MDD episode or no history of MDD. Third, providing initial evidence of brain regions underlying these effects using archival rat brain tissue, we show that an acute stressor increased IL-33 expression in the paraventricular nucleus of the hypothalamus and, to a lesser extent, the prefrontal cortex, key brain regions underlying stress response and emotion regulation. These findings provide converging support for the potential role of IL-33 in risk for recurrent MDD. (PsycINFO Database Record
authors.affiliation: Center for Affective Science, Binghamton University (SUNY).
authors.forename: Anastacia Y
authors.initials: AY
authors.lastname: Kudinova
authors.affiliation: Center for Affective Science, Binghamton University (SUNY).
authors.forename: Terrence
authors.initials: T
authors.lastname: Deak
authors.affiliation: Center for Affective Science, Binghamton University (SUNY).
authors.forename: Cara M
authors.initials: CM
authors.lastname: Hueston
authors.affiliation: Providence Veterans Affairs Medical Center.
authors.forename: John E
authors.initials: JE
authors.lastname: McGeary
authors.affiliation: Division of Behavioral Genetics, Rhode Island Hospital.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Knopik
authors.affiliation: Division of Behavioral Genetics, Rhode Island Hospital.
authors.forename: Rohan H C
authors.initials: RH
authors.lastname: Palmer
authors.affiliation: Center for Affective Science, Binghamton University (SUNY).
authors.forename: Brandon E
authors.initials: BE
authors.lastname: Gibb
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism; D003865:Major Depressive Disorder / Q000097:blood* / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006239:Haplotypes; D006801:Humans; D000067596:Interleukin-33 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D000067596:Interleukin-33