The role of cytokines in the pathophysiology of suicidal behavior

Abstract

Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors. Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk.

Association of suicidal ideation with poor sleep quality among Ethiopian adults

“…Alterations of the HPA axis, observed among individuals with suicidal ideation and depressive disorders, may well be one mechanism underlying the consistently observed statistical association of sleep disturbance and suicidal ideation. In a recent study, suicidal patients, as compared with their non-suicidal counterparts, were found to have chronic systemic inflammation, as evidenced by their higher plasma or serum concentrations of pro-inflammatory cytokines including interleukin-1β, interleukin-6, interleukin-10, C-reactive protein, and tumor necrosis factor-α [30]. In addition to these hypothesized neuroendocrine and proinflammatory mechanism, some investigators have posited that shared psychosocial and behavioral mechanisms, including adverse life events, psychiatric conditions and physical inactivity [26, 27] may explain the observed associations.…”

Air pollution, aeroallergens and suicidality: a review of the effects of air pollution and aeroallergens on suicidal behavior and an exploration of possible mechanisms

“…Interestingly, the role of cytokines in suicidal behavior is contrary to what would be expected; previous evidence has suggested increases in interferon gamma (IFN)-γ, which down regulates the production of IgE. Moreover, an association between increased levels of IL-4 and suicide was only demonstrated in one study (121). Notwithstanding the foregoing results, IgE status has been associated with increased depression scores indicating worse mood symptoms (122).…”

Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review

“…In regard to the type of depressive symptoms, Capuron et al only observed that IL-6 appeared to be related to the “reduced appetite” score of the Montgomery–Asberg Depression Rating Scale in elderly subjects [47]. Moreover, a recently published review concluded that IL-6 is the cytokine most robustly associated with suicidal ideation, suicides, and nonfatal suicide attempts [48], thereby suggesting an important role of this interleukin in this aspect of depression. The authors found that the results for other inflammatory parameters were inconclusive.…”