Jergović Mladen, Bendelja Krešo, Savić Mlakar Ana, Vojvoda Valerija, Aberle Neda, Jovanovic Tanja, Rabatić Sabina, Sabioncello Ante, Vidović Anđelko
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb , Zagreb , Croatia ; Department for Cellular Immunology, Institute of Immunology , Zagreb , Croatia.
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb , Zagreb , Croatia.
Front Psychiatry. 2015 Apr 14;6:49. doi: 10.3389/fpsyt.2015.00049. eCollection 2015.
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.
许多外周血分析物已被提议作为创伤后应激障碍（PTSD）的潜在生物标志物。很少有研究调查生物标志物中观察到的变化是否会随时间持续存在。本研究的目的是调查与战斗相关的慢性创伤后应激障碍与一系列假定的创伤后应激障碍生物标志物之间的关联，并确定测量的可靠性，即随时间的相关性。对患有慢性创伤后应激障碍的克罗地亚退伍军人（n = 69）和年龄匹配的健康对照者（n = 32），均为男性，在相隔3个月的两个时间点进行评估。测定血清中的脂质、皮质醇、硫酸脱氢表雄酮（DHEA-S）、催乳素和C反应蛋白水平。采用多重分析法同时评估血清中的13种分析物：细胞因子[干扰素-γ、白细胞介素（IL）-1β、IL-2、IL-4、IL-6、肿瘤坏死因子-α]、黏附分子（可溶性血小板内皮细胞黏附分子-1、可溶性细胞间黏附分子-1）、趋化因子（IL-8和巨噬细胞炎性蛋白-1α）、可溶性CD40配体、神经生长因子和瘦素。通过参数检验或非参数检验，包括重复测量协方差分析，来检验组间差异和随时间的变化。还计算了可靠性估计值[组内相关系数（ICC）和kappa值]。发现创伤后应激障碍与较高水平的DHEA-S [F(1,75) = 8.14，p = 0.006]和较低水平的催乳素[F(1,75) = 5.40，p = 0.023]之间存在显著关联。测量显示出良好到优异的可重复性（DHEA-S，ICC = 0.50；催乳素，ICC = 0.79）。两组之间血清脂质无差异，但创伤后应激障碍组在3个月后观察到低密度脂蛋白胆固醇显著升高（t = 6.87，p < 0.001）。创伤后应激障碍组的IL-8较低（t = 4.37，p < 0.001），但评估显示可重复性较差（ICC = -0.08）。稳定的DHEA-S和催乳素变化突出了它们作为创伤后应激障碍可靠标志物的潜力。3个月后脂质谱的变化表明创伤后应激障碍患者可能更容易患高脂血症。某些变量中较高的个体内变异性强调了纵向研究在创伤后应激障碍生物标志物研究中的重要性。
