Article

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

New York University School of Medicine , NYU Child Study Center, New York, New York 10016, USA.
Journal of child and adolescent psychopharmacology (Impact Factor: 2.93). 08/2009; 19(4):423-30. DOI: 10.1089/cap.2008.0140
Source: PubMed

ABSTRACT

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-1beta, and (2) a proinflammatory/antiinflammatory cytokine imbalance (indexed by plasma IFN-gamma/IL-4), compared to nonsuicidal depressed adolescents and healthy controls.
Twelve suicidal adolescents with MDD (7 females [58%]; 5 medication-free/naïve), 18 nonsuicidal adolescents with MDD (12 females [67%]; 8 medication-free/naïve), 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.
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.
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.

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    • "There is strong support for the role of inflammation in the pathogenesis of both MDD[15,22,38]and other psychiatric disorders[42]. Work in our lab has documented immune system dysregulation and increased levels of proinflammatory cytokines – proteins that function as signaling molecules to modulate immune responses – in adolescent MDD[15,16]. Cytokines also interact with mitochondria to increase the production of reactive oxygen species (ROS), and ROS, through a recurring cycle, further activate cytokines and evoke an inflammatory response[51,41]. "
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    • "Recent systematic review by Mills et al. (2013) supports the view that depression in adolescents is a low-grade neuro-inflammation state. The role of pro-inflammatory cytokines, such as IL-1β, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, IL-6 etc. in the etiology and pathophysiology of depression is well investigated (O'Brien et al., 2007; Dhabhar et al., 2009; Dowlati et al., 2010; Janelidze et al., 2011) including their in suicidality (Simon et al., 2008; Gabbay et al., 2009b). In contrast to pro-inflammatory cytokines such as IL-6, considerably less attention has been focused on the potential role of anti-inflammatory (IL-10), immunomodulatory (TGF-β1) and autoimmune (IL-17) cytokines. "
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    ABSTRACT: The present study compares the serum cytokine levels between adolescent depression patients and healthy controls and assesses correlation between depression, anxiety scores and serum levels of eight cytokines. Study also checked the variation in serum levels with medication status (medication free/naïve vs. patients on medication). Following clinical and psychometric assessment of 77 adolescent (aged 13-18 years) depression patients (49 males and 28 females; 56 medication free/naïve) and 54 healthy controls (25 males, 29 females), eight cytokines (IL-1β, IL-2, IL-6, IL-10, TNF-α, IFN-γ, TGF-β1 and IL-17A {denoted IL-17 throughout}) were measured in serum using ELISA. Depressed adolescents had significantly high levels of IL-2 (p<0.001) and IL-6 (p=0.03) as compared to controls. The female population skewed the result of one cytokine (IL-6) in patients. Anxiety scores showed positive correlation (only in female patients) with IL-1β, IL-10 and negative correlation with TGF-β1 and IL-17. The gender effect in relationship between anxiety and cytokines was not straightforward. On comparing study groups on the medication/naïve status, IL-2 and TGF-β1 showed significant difference between the groups (p<0.001, p=0.007 higher in medicated). Depression in adolescents was associated with elevation of proinflammatory serum cytokines with a gender bias for females. Anxiety scores correlated negatively with TGF-β1 and IL-17. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Jun 2015
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    • "The current sample is part of previous published studies examining a) plasma cytokine levels in suicidal depressed adolescents (Gabbay et al., 2009) and b) the KP in adolescent MDD (Gabbay et al., 2010a). Participants were 30 non-suicidal adolescents with MDD (mean age¼15. "
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