A Preliminary Study of Cytokines in Suicidal and Nonsuicidal Adolescents with Major Depression

Background: Increased systemic cytokine levels, modulators of the immune system, have been repeatedly documented in adult and adolescent major depressive disorder (MDD). This preliminary study extends this work to test the role of cytokines in suicidal symptomatology in adolescent MDD. Hypotheses were that acutely suicidal depressed adolescents would have: (1) increased plasma levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1b, and (2) a proinflammatory/antiinflammatory cytokine imbalance (indexed by plasma IFN-gamma/IL-4), compared to nonsuicidal depressed adolescents and healthy controls. Methods: Twelve suicidal adolescents with MDD (7 females [58%]; 5 medication-free/naive), 18 nonsuicidal adolescents with MDD (12 females [67%]; 8 medication-free/naive), and 15 controls (8 females [53%]) were enrolled. MDD had to be of at least 6 weeks duration, with a minimum severity score of 40 on the Children's Depression Rating Scale-Revised. Plasma cytokines were examined using enzyme-linked immunosorbent assays. Nonparametric tests were used to compare subject groups. Results: Unexpectedly, suicidal adolescents with MDD had significantly decreased plasma TNF-alpha concentrations compared to nonsuicidal adolescents with MDD (1.33 +/- 2.95 pg/mL versus 30.9 +/- 110.9 pg/mL; p = 0.03). IFN-gamma was increased in both suicidal and nonsuicidal adolescents with MDD compared to controls (2.14 +/- 6.22 and 4.20 +/- 14.48 versus 0.37 +/- 0.64; p<0.02, p = 0.005). Findings remained evident when controlled for age and gender. Conclusions: Our preliminary findings suggest that immune system dysregulation may be associated with suicidal symptomatology in adolescent MDD. These findings should be replicated in larger samples with medication-free adolescents.