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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 11 th 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.

Background: Changes in serum concentrations of tumor necrosis factor-α (TNF-α) and its soluble receptors (sTNF-R) p55 and p75 have been shown to be associated with various psychiatric treatments., Subjects and Methods: Before and after treatment, serum levels of TNF-α, sTNF-R p55 and sTNF-R p75 were measured in 38 German soldiers who had been deployed abroad and suffered from combat-related post-traumatic stress disorder (PTSD). Patients were randomized either to inpatient psychotherapy (N=21) including eye movement desensitization and reprocessing (EMDR) or to outpatient clinical management (N=17). Symptoms of PTSD were measured using the Post-traumatic Stress Diagnostic Scale (PDS)., Results: The PDS score significantly decreased across time in both groups. Serum concentrations of TNF-α increased, while sTNF-R p55 and sTNF-R p75 levels decreased significantly. After the treatment period, we could not detect any significant difference regarding TNF-α, sTNF-R p55 or sTNF-R p75 levels between the inpatient psychotherapy group and the outpatient clinical management control group., Conclusions: This relatively small clinical study suggests that specific inpatient psychotherapy but also non-specific supportive outpatient treatment for PTSD are associated with changes in the TNF-α system. This may represent an immunological effects or side effects of psychotherapy.

Growing evidence suggests involvement of the tumor necrosis factor (TNF)-α system in the pathophysiology of psychiatric disorders. Research into post-traumatic stress disorder (PTSD) has investigated serum levels of TNF-α, but not to date its soluble receptors sTNF-R p55 and sTNF-R p75. We examined serum levels of TNF-α, sTNF-R p55 and sTNF-R p75 in 135 male German soldiers 70 of whom had been deployed abroad and 65 in Germany only. Post-traumatic stress symptoms were measured using the Post-traumatic Stress Diagnostic Scale (PDS) and the Trier Inventory for the Assessment of Chronic Stress (TICS). Correlational analysis controlling for multiple testing, showed no significant Spearman rank correlations between PDS or TICS scores and serum levels of TNF-α, sTNF-R p55 or sTNF-R p75, either in the full sample or in the group of soldiers who had been deployed abroad. ANCOVAs showed no significant differences between soldiers with or without a PDS-derived diagnosis of PTSD, or between soldiers with or without deployment abroad, after controlling for age, smoking and body mass index (BMI). These results suggest that the TNF-α system, as reflected by TNF-α, sTNF-R p55 and sTNF-R p75 serum levels, does not play a major role in the pathophysiology and development of PTSD symptoms as measured by the PDS and the TICS. However, several methodological and contextual issues have to be considered.