AUTHOR=Sun Shengnan , Wilson Caroline M. , Alter Sharon , Ge Yongchao , Hazlett Erin A. , Goodman Marianne , Yehuda Rachel , Galfalvy Hanga , Haghighi Fatemeh 

TITLE=Association of interleukin-6 with suicidal ideation in veterans: a longitudinal perspective

JOURNAL=Frontiers in Psychiatry

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1231031

DOI=10.3389/fpsyt.2023.1231031

ISSN=1664-0640

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>Studies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally.</p></sec><sec id="sec2"><title>Methods</title><p>Veterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA <italic>n</italic> = 38, MDD/NS <italic>n</italic> = 41) and non-psychiatric non-attempter controls (HC <italic>n</italic> = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology.</p></sec><sec id="sec3"><title>Results</title><p>Significant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1β, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (<italic>p</italic> = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction <italic>F</italic><sub>1,91.77</sub> = 5.58, <italic>p</italic> = 0.0203) and TNF-α (<italic>F</italic><sub>1,101.73</sub> = 4.69, <italic>p</italic> = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: <italic>b</italic> = −0.04, 95% CI = (−0.08, −0.01), <italic>p</italic> = 0.0245 and TNF-α: <italic>b</italic> = −0.02, 95% CI = (−0.04, −0.01), <italic>p</italic> = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), <italic>p</italic> = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (<italic>b</italic> = 0.19, <italic>p</italic> = 0.0422).</p></sec><sec id="sec4"><title>Discussion</title><p>IL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk.</p></sec>