Journal
PSYCHONEUROENDOCRINOLOGY
Volume 111, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2019.104487
Keywords
Depression; Suicidality; Suicide behavior; Adaptive immunity; Autoimmunity; IL-4; Type 2 immune response
Categories
Funding
- W.W. Caruth Jr. Foundation
- REDCap [UL1 TR001105]
- Center for Depression Research and Clinical Care
- Hersh Foundation
- National Institute of Mental Health (NIMH) [N01 MH90003]
- Acadia Pharmaceutical
- Janssen Research
- NIMH
- NIDA
- JJ
- Janssen Research and Development LLC
- NARSAD
- Duke University
- Forest Research Institute, Inc.
- Janssen Pharmaceuticals
- Elizabeth Jordan Harris Foundation
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Background: Immune system dysfunction has been implicated in the pathophysiology of suicide behavior. Here, we conducted an exploratory analysis of immune profile differences of three groups of adolescents and young adults (ages 10-25 years): healthy controls (n = 39), at risk of major depressive disorder (MDD; at-risk, n = 33), and MDD with recent suicide behavior/ ideation (suicide behavior, n = 37). Methods: Plasma samples were assayed for chemokines and cytokines using Bio-Plex Pro Human Chemokine 40-plex assay. Log-transformed cytokine and chemokine levels were compared after controlling for age, gender, body mass index, race, ethnicity, and C-reactive protein (CRP) levels. In post-hoc analyses to understand the effect of dysregulated immune markers identified in this exploratory analysis, their association with auto-antibodies was tested in an unrelated sample (n = 166). Results: Only levels of interleukin 4 (IL-4) differed significantly among the three groups [false discovery rate (FDR) adjusted p = 0.0007]. Participants with suicide behavior had lower IL-4 [median = 16.8 pg/ml, interquartile range (IQR) = 7.9] levels than healthy controls (median = 29.1 pg/ml, IQR = 16.1, effect size [ES] = 1.30) and those at-risk (median = 24.4 pg/ml, IQR = 16.3, ES = 1.03). IL-4 levels were negatively correlated with depression severity (r= -0.38, p = 0.024). In an unrelated sample of outpatients with MDD, levels of IL-4 were negatively correlated (all FDR p < 0.05) with several autoantibodies [54/117 in total and 12/18 against innate immune markers]. Conclusions: Adolescent and young adult patients with recent suicide behavior exhibit lower IL-4 levels. One biological consequence of reduced IL-4 levels may be increased risk of autoimmunity.
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