title: Immune system dysregulation in adolescent major depressive disorder.
abstract: BACKGROUND
  A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-gamma, tumor necrosis factor-alpha, interleukin [IL]-6, IL-1beta, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-gamma/IL-4.
  
  
  METHODS
  Thirty adolescents with MDD (19 females; 13 medication-free/naïve; ages 12-19) of at least 6 weeks duration and a minimum severity score of 40 on the Children's Depression Rating Scale-Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann-Whitney test was used to compare subjects with MDD and controls.
  
  
  RESULTS
  Adolescents with MDD had significantly elevated plasma IFN-gamma levels (3.38+/-11.8 pg/ml versus 0.37+/-0.64 pg/ml; p<0.003), and IFN-gamma/IL-4 ratio (16.6+/-56.5 versus 1.76+/-2.28; p=0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52+/-2.88 pg/ml versus 0.49+/-0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded.
  
  
  CONCLUSIONS
  Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow.
authors.affiliation: New York University School of Medicine, NYU Child Study Center, NY 10016, United States. vilma.gabbay@nyumc.org
authors.forename: Vilma
authors.initials: V
authors.lastname: Gabbay
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Klein
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Alonso
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
authors.forename: Melissa
authors.initials: M
authors.lastname: Nishawala
authors.forename: Georgette
authors.initials: G
authors.lastname: De Jesus
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Hirsch
authors.forename: Pauline M Z
authors.initials: PM
authors.lastname: Hottinger-Blanc
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Gonzalez
mesh_terms: D000293:Adolescent; D002648:Child; D016207:Cytokines / Q000097:blood*; D003865:Major Depressive Disorder / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D012016:Reference Values; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines
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