Abstract
A number of peripheral blood analytes have been proposed as potential biomarkers of post-traumatic stress disorder (PTSD). Few studies have investigated whether observed changes in biomarkers persist over time. The aim of this study was to investigate the association of combat-related chronic PTSD with a wide array of putative PTSD biomarkers and to determine reliability of the measurements, i.e., correlations over time. Croatian combat veterans with chronic PTSD (n = 69) and age-matched healthy controls (n = 32), all men, were assessed at two time points separated by 3 months. Serum levels of lipids, cortisol, dehydroepiandrosterone-sulfate (DHEA-S), prolactin, and C-reactive protein were determined. Multiplex assay was used for the simultaneous assessment of 13 analytes in sera: cytokines [interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, TNF-α], adhesion molecules (sPECAM-1, sICAM-1), chemokines (IL-8 and MIP-1α), sCD40L, nerve growth factor, and leptin. Group differences and changes over time were tested by parametric or non-parametric tests, including repeated measures analysis of covariance. Reliability estimates [intraclass correlation coefficient (ICC) and kappa] were also calculated. Robust associations of PTSD with higher levels of DHEA-S [F(1,75) = 8.14, p = 0.006)] and lower levels of prolactin [F(1,75) = 5.40, p = 0.023] were found. Measurements showed good to excellent reproducibility (DHEA-S, ICC = 0.50; prolactin, ICC = 0.79). Serum lipids did not differ between groups but significant increase of LDL-C after 3 months was observed in the PTSD group (t = 6.87, p < 0.001). IL-8 was lower in the PTSD group (t = 4.37, p < 0.001) but assessments showed poor reproducibility (ICC = −0.08). Stable DHEA-S and prolactin changes highlight their potential to be reliable markers of PTSD. Change in lipid profiles after 3 months suggests that PTSD patients may be more prone to hyperlipidemia. High intra-individual variability in some variables emphasizes the importance of longitudinal studies in investigations of PTSD biomarkers.
Highlights
Long-term mental and physical health consequences of trauma place a significant burden on healthcare systems, especially in areas with a recent history of conflict where the majority of the population has been affected by war [1, 2]
Beck Depression Inventory (BDI) scores declined in Post-traumatic stress disorder (PTSD) patients (12.3 ± 10.2, t = 12.08, p < 0.001) but remained elevated in comparison to controls at the second assessment (4.7 ± 6.3, t = 4.13, p < 0.001)
We found a robust association of combat-related chronic PTSD with higher serum levels of DHEA-S and lower levels of prolactin
Summary
Long-term mental and physical health consequences of trauma place a significant burden on healthcare systems, especially in areas with a recent history of conflict where the majority of the population has been affected by war [1, 2]. There is substantial evidence for dysregulation of the hypothalamic– pituitary–adrenal (HPA) axis with decreased levels of blood and urinary cortisol and enhanced sensitivity of the HPA axis to negative feedback [18]. These alterations could influence lipid metabolism [19] and contribute to immune system activation leading to peripheral inflammation reflected by elevated circulating levels of cytokines and acute phase reactant C-reactive protein (CRP) [20]. Given the complex neuroendocrine–immune interactions observed in PTSD, researchers have utilized assays that allow for simultaneous detection of multiple analytes in a limited amount of sample and found a broad spectrum of increased circulating www.frontiersin.org
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