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: 3.07). 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.

Download full-text

Full-text

Available from: Rachel G Klein, Jun 27, 2015
0 Followers
 · 
134 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A series of evidence suggests that interferon-gamma (IFN-γ) plays an important role in central nervous system (CNS) functions. However, previous studies have obtained inconsistent results regarding the role of IFN-γ in modulating emotion-related behaviors. The present study aimed to evaluate the behavioral profile of IFN-γ knockout (K.O.) mice in models of anxiety and depression. Male C57Bl6 wild type (WT) or IFN-γ K.O. mice were submitted to the following tests: contextual fear conditioning (CFC), elevated plus maze (EPM), open field (OF) and forced swimming test (FST). To explore the possible neurobiological mechanisms involved, we also assessed hippocampal neurogenesis by means of hippocampal doublecortin expression, and the levels of Brain-Derived Neurothophic Factor (BDNF) and Nerve Growth Factor (NGF) in the hippocampus and prefrontal cortex. Our results suggested that IFN-γ K.O. mice exhibited an anxiogenic profile in CFC, EPM and OF tests. In FST, the K.O. group spent more time immobile than the WT group. The number of doublecortin positive cells was reduced in the dentate gyrus, and the expression of NGF was down regulated in the prefrontal cortex of IFN-γ K.O. mice. Our results suggest that IFN-γ is involved in CNS plasticity, contributing to the modulation of anxiety e depressive states.
    Neuroscience Letters 06/2014; DOI:10.1016/j.neulet.2014.06.039 · 2.06 Impact Factor
  • Source
    Neurology Psychiatry and Brain Research 02/2014; 20(1):22. DOI:10.1016/j.npbr.2014.01.168 · 0.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is growing evidence that inflammatory mediators play a critical role in the pathophysiology of both major depression and suicidal behavior. Immunological differences have been reported in both major affective disorders and suicidal behavior. Specifically, increased levels of pro-inflammatory cytokines have been shown to correlate with the severity of depression and various cytokines have been identified as potentially important in understanding the pathophysiology of major affective disorders/suicidality. We aimed to conduct a systematic review of the current literature to investigate the association between inflammatory cytokines and suicidal behavior. Only articles from peer-reviewed journals were selected for inclusion in the present review. Most studies documented the association between suicidality and IL2, IL-6, IL-8, TNF-α and VEGF levels that have been found altered in suicidal behavior. The presence of major depressive disorder (MDD) with suicidal ideation/attempts was associated with differences in inflammatory cytokine profile when compared to that without suicidal ideation/attempts. Most suicide attempters or subjects with suicidal ideation showed an imbalance of the immune system but this does not imply the existence of a causal link. Also, not all studies demonstrated a positive correlation between inflammatory cytokines and suicidal behavior. Further additional studies should elucidate the molecular mechanisms of the immune activation pathways underlying suicidality.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2013; 23(12). DOI:10.1016/j.euroneuro.2013.06.002 · 5.40 Impact Factor