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

Abstract

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.

Meta-Analysis of Cytokines and Chemokines in Suicidality: Distinguishing Suicidal Versus Nonsuicidal Patients

“…A common comorbid diagnosis among other psychiatric diagnoses is MDD, and the association between cytokines and suicidality may be mediated through MDD (12). Of the 18 included studies, 8 (17,19,20,25,29,31,33,34) included suicidal subjects with different primary and comorbid diagnoses. Studies that defined suicidality as a prior or recent suicide attempt were more likely to include a patient population with different primary diagnoses, as were postmortem studies of completed suicides.…”

Increased levels of vascular endothelial growth factor in patients with major depressive disorder: A meta-analysis

“…After screening the remaining 46 articles in step 2, a total of 16 remained in the current meta-analysis. In addition, we re-included one article in the meta-analysis of correlations between VEGF and severity of disease (Isung et al, 2012). The results of the literature search are listed in Table 1 (Berent et al, 2014;Carvalho et al, 2014Carvalho et al, , 2013Clark-Raymond et al, 2014;Dalby et al, 2013;Dome et al, 2009;Elfving et al, 2014;Fornaro et al, 2013;Galecki et al, 2013a;Kahl et al, 2009;Kotan et al, 2012;Lee and Kim, 2012;Lu et al, 2013;Schweiger et al, 2008;Takebayashi et al, 2010;Ventriglia et al, 2009).…”

“…Many studies have reported on the significant difference between VEGF expression in patients with MDD and healthy controls. Isung and colleagues recruited a group who had attempted suicide, most of whom fulfilled the diagnosis of mood disorders in DSM (Diagnostic and Statistical Manual of Mental Disorders) axis I, and found lower VEGF levels in their cerebrospinal fluid than in healthy controls (Isung et al, 2012). In addition, many studies have demonstrated an increase in peripheral VEGF in MDD patients compared with healthy controls, either in serum (Berent et al, 2014;Carvalho et al, 2014;Elfving et al, 2014;Galecki et al, 2013a;Kahl et al, 2009;Schweiger et al, 2008) or plasma (Lee and Kim, 2012;Lu et al, 2013;Takebayashi et al, 2010).…”

Inflammatory markers and suicidal attempts in depressed patients: A review

“…No significant groups differences were reported for IL-4, 76 TGF-1β 76,78 plasma levels and IL-1β 79 CSF levels. Regarding IL-6, two authors reported no Isung et al 40 43 suicide attempters, 20 controls…”

“…significant differences between groups in plasma 76 and CSF concentrations. 40 Three authors found increased IL-6 plasma 77,78 and CSF 79 levels. Increased IFN-γ 76 and IL-10 plasma levels were reported.…”