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

J Isung,B Mårtensson,P Nordström,F Mobarrez,F Piehl,J Jokinen,S Aeinehband,M Åsberg

doi:10.1038/tp.2012.123

J Isung, B Mårtensson + Show 6 more

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https://doi.org/10.1038/tp.2012.123

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Journal: Translational Psychiatry	Publication Date: Nov 1, 2012
Citations: 81	License type: cc-by

Affiliation: Karolinska Institutet

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.

Highlights

The neurotrophic and neurogenesis hypothesis postulates that growth factor disturbances are important in the pathogenesis of neuropsychiatric disorders such as depression
cerebrospinal fluid (CSF) vascular endothelial growth factor-A (VEGF) and IL-8 levels were significantly lower in suicide attempters (VEGF mean 3.7 pg ml À 1, IL À 8 mean 17.1 pg ml À 1) compared with controls (VEGF mean 5.0 pg ml À 1, IL-8 mean 25.6 pg ml À 1) (t-ratio 1⁄4 À 3.76, P 1⁄4 0.0004; t-ratio 1⁄4 À 5.82, Po0.0001, both adjusted for age) (Figure 1, 2)
The levels of CSF VEGF and IL-8 did not correlate with plasma levels of VEGF and IL-8 in suicide attempters (Spearman’s rho 1⁄4 0.04, P 1⁄4 0.80; Spearman’s rho 1⁄4 0.06, P 1⁄4 0.70)

Summary

Introduction

The neurotrophic and neurogenesis hypothesis postulates that growth factor disturbances are important in the pathogenesis of neuropsychiatric disorders such as depression. We analyzed CSF cytokines and vascular endothelial growth factor-A (VEGF) with a sensitive immunoassay system in medication-free suicide attempters and healthy volunteers. We hypothesized that growth factor levels, as well as proinflammatory cytokines would differentiate in the CSF of patients with a recent suicide attempt, as compared with healthy controls

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Conclusion