Association between baseline pro-inflammatory cytokines and brain activation during social exclusion in patients with vulnerability to suicide and depressive disorder

A Specific Inflammatory Profile Underlying Suicide Risk? Systematic Review of the Main Literature Findings

“…Overall, 11 studies analyzed the existence of inflammatory cytokines abnormalities in suicidal vs. nonsuicidal healthy controls. Recently, Conejero et al [25] reported that IL-1β was negatively associated with right orbitofrontal cortex (OFC) activation during the explicit social exclusion vs. social inclusion, whereas IL-2 was positively associated with activation of the right anterior cingulate cortex (ACC), insula and OFC even after controlling independently for the suicidal status. Moreover, Pandey et al [4] found that IL-1β, IL-6, TNF-α, and lymphotoxin A mRNA and protein levels were significantly increased, while IL-10 and IL-1 receptor antagonists (IL-1ra) were reduced in the prefrontal cortex (PFC) of depressed individuals who died by suicide compared to healthy controls.…”

“…However, based on the selected studies and in line with a previously published paper of our research group upon the same topic [7], the existence of an association between inflammatory cytokines abnormalities and suicidal behavior does not necessarily reflect a specific causal link. Among the selected studies, eleven reports [8,9,12,[25][26][27][28][29][30][31][32] analyzed inflammatory cytokines abnormalities in suicidal patients, four [33][34][35][36] explored cytokines abnormalities in patients with both a positive history of suicide attempts and suicidal ideation, two [37,38] investigated the existence of inflammatory cytokines abnormalities levels in depressed patients with suicidal ideation vs. those abnormally without, seven [31,[40][41][42][43][44]50] examined the inflammatory cytokines abnormalities in patients with a history of suicide attempts vs. those without, three [45][46][47] analyzed patients died by suicide vs. those died for other causes, and two [48,49] focused on depressed suicidal patients with suicidality.…”

“…According to our findings, the most consistent link between inflammatory changes and suicidal behavior may be found in studies directly analyzing cytokines abnormalities and suicidal patients (completed suicides or those with a history of suicide attempts) when compared to healthy controls. Most of these studies documented abnormally higher levels of IL-1β, IL-6, TNF-α, TGF-β1, VEGF, and KYN, and lower levels of IL-2, IL-4, and IFN-γ predominantly in specific brain regions such as OFC, right ACC, insula, and dlPFC of suicidal patients (mainly suicide attempters) [8,9,12,[25][26][27][28][29][30][31][32]39,42,43]. Abnormally elevated IL-6 and IL-10 levels have also been reported in patients with active suicidal ideation when compared to healthy controls [37].…”

“…In addition, inflammatory cytokines may lead to significant behavioral and emotional changes according to their direct effects in specific brain regions [53]. However, other studies support the notion that the inflammatory modulation of the neural response to social exclusion may be directly related to specific psychiatric conditions, independently of suicidal behavior [25]. To this specific regard, the authors found that IL-1β was negatively associated with right OFC activation in explicit social exclusion vs. social inclusion, whereas IL-2 was positively associated with activation of the right ACC insula and OFC in explicit social exclusion vs. social inclusion, even after controlling for group, indicating that these changes were independent of suicidal status.…”

Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

“…Previous studies have found that in ammation was associated with abnormal brain activation and functional connectivity in limbic network [34,35]. The limbic network, which includes the hippocampus, para-hippocampal gyrus, amygdala, orbitofrontal cortex (OFC), cingulate gyrus [36], involves in various functions such as emotional processing and regulation [37,38] and reward processing [39,40], and plays a critical role in emotional dysregulation in BD [11,41].…”