A Systematic Review of Tumor Necrosis Factor-α in Post-Traumatic Stress Disorder: Evidence from Human and Animal Studies

BACKGROUND: Growing evidence suggests a pathophysiological role of cytokines in post-traumatic stress disorder (PTSD). Tumor necrosis factor (TNF)-α is a key cytokine. Therefore, we performed a systematic review to examine the findings regarding TNF-α derived from both animal and human studies of PTSD.

METHODS: Using PRISMA guidelines, we reviewed relevant articles in PubMed from inception until 11th April 2017. Human studies that reported group comparisons and/or longitudinal investigations of TNF-α production/concentration were included. Research reporting on TNF-α levels in animal models of PTSD were also included.

RESULTS: Twenty-seven articles were identified. Data from human cross-sectional studies suggests that plasma/serum levels of TNF-α are elevated in those with PTSD, as compared to healthy controls. Longitudinal assessments of TNF-α are limited and data are mixed. Limited data from animal studies suggest an increased TNF-α production in the hippocampus of rats following stress, which can be reversed by immunomodulatory drugs.

CONCLUSIONS: Our findings suggest TNF-α may be a potential biomarker and treatment target for PTSD. Findings need to be considered in light of heterogeneous methods for measurement and analysis of TNF-α concentration. Longitudinal research is needed to understand the role of TNF-α in the development and/or maintenance of PTSD.