High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide.

The dysregulation of inflammation has been associated with depression and, more recently, with suicidal behaviors. The reports regarding the relationship between interleukin-6 (IL-6) and suicide attempts are inconsistent. Personality traits such as impulsivity and aggression are considered endophenotypes and important factors that underlie suicidal behaviors. The aim of the current study was to assess whether plasma and cerebrospinal fluid (CSF) levels of IL-6 are associated with personality traits among suicide attempters. We assessed the relationships among personality traits, IL-6 and violent suicide attempts. The plasma and CSF levels of IL-6 were measured in suicide attempters (plasma=58, CSF=39) using antibody-based immunoassay systems. Personality domains were assessed using the Karolinska Scale of Personality (KSP). IL-6 levels in plasma and CSF were used to predict personality domains via regression models. Plasma IL-6 was significantly and positively correlated with extraversion as well as the KSP subscales impulsivity and monotony avoidance. CSF IL-6 was positively correlated with monotony avoidance. Violent suicide attempts tended to be associated with high plasma IL-6 levels. Plasma and CSF levels of IL-6 were not significantly associated with each other. These results indicate that impulsivity and the choice of a violent suicide attempt method might be related to higher levels of IL-6 in individuals who attempt suicide. The neuroinflammation hypothesis of suicidal behavior on the basis of elevated IL-6 levels might be partly explained by the positive association between IL-6 and impulsivity, which is a key element of the suicidal phenotype.

Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid of suicide attempters.

A dysregulated immune system influencing pathways for cytokine regulation and growth factor expression is implicated in the pathophysiology of several neuropsychiatric disorders. Here, we analyzed cerebrospinal fluid (CSF) cytokines and growth factors with an ultra-sensitive immunoassay system in 43 medication-free suicide attempters and 20 healthy male volunteers. CSF vascular endothelial growth factor (VEGF) and CSF interleukin-8 (IL-8) levels were significantly lower in suicide attempters compared with healthy controls. Further, CSF VEGF showed a significant negative correlation with depression severity. CSF IL-6 levels did not differ between suicide attempters and healthy controls. Low CSF levels of VEGF may represent a lack of trophic support to neurons and downregulation of neurogenesis in the hippocampus reflecting more severe depressive states. IL-8 has also been reported as important in neuroprotection as well as having chemokine activity in the innate immune response. The results support a role for an impaired innate immunity and dysregulation of neuroprotection in the pathophysiology of depression and suicidal behavior.