Tomlinson Cassidy J, Ryniker Laura, Cook Haley M, Schwartz Rebecca M, Non Amy L
Department of Anthropology, University of California San Diego, La Jolla, CA, USA.
Department of Occupational Medicine, Epidemiology and Prevention, Northwell Health, Great Neck, NY, USA.
Epigenomics. 2025 Apr;17(5):297-307. doi: 10.1080/17501911.2025.2476389. Epub 2025 Mar 11.
People living with HIV (PLWH) have an increased risk for lifetime trauma and mental health difficulties. However, no studies have evaluated stress-related genes in relation to early-life adversity, lifetime trauma, or post-traumatic stress disorder (PTSD) in PLWH.
Using bisulfite pyrosequencing, we evaluated DNA methylation (DNAm) in intron 7 of FKBP5, a glucocorticoid feedback regulator, and in the promoter of SLC6A4, the serotonin transporter gene, in whole blood of a random sample of 70 PLWH recruited from an HIV program, and 51 individuals 2 years later ( = 48 at both time points). Exploratory regression analyses were conducted with DNAm in relation to trauma exposure, mental health symptoms, and coping strategies.
Higher DNAm at one site of SLC6A4 was associated with lower levels of anxiety (B = -0.62 (SE = 0.23), = 0.0109), depression (B = -0.06 (SE = 0.03), = 0.0435), and PTSD symptoms at baseline (B = -0.03 (SE = 0.01), = 0.0374). DNAm at FKBP5 was negatively associated with measures of anxiety (B = -0.30 (SE = 0.07), = 0.0001) and depression symptoms (B = -0.2 (SE = 0.10), = 0.0103). Various coping strategies were also associated with sites in both genes across time points, e.g. self-blame and substance use.
Our findings generate intriguing hypotheses linking mental health symptoms and DNA methylation, to be replicated with larger samples.
人类免疫缺陷病毒感染者（PLWH）一生中遭受创伤和出现心理健康问题的风险增加。然而，尚无研究评估与应激相关的基因与PLWH早年逆境、一生创伤或创伤后应激障碍（PTSD）之间的关系。
我们采用亚硫酸氢盐焦磷酸测序法，评估了从一个艾滋病项目中随机抽取的70名PLWH全血中糖皮质激素反馈调节因子FKBP5第7内含子以及血清素转运体基因SLC6A4启动子区域的DNA甲基化（DNAm）情况，并在两年后对51名个体进行了评估（两个时间点均为48名个体）。对DNAm与创伤暴露、心理健康症状及应对策略进行了探索性回归分析。
SLC6A4一个位点的较高DNAm与较低水平的焦虑（B = -0.62（标准误 = 0.23），P = 0.0109）、抑郁（B = -0.06（标准误 = 0.03），P = 0.0435）以及基线时的PTSD症状（B = -0.03（标准误 = 0.01），P = 0.0374）相关。FKBP5的DNAm与焦虑测量值（B = -0.30（标准误 = 0.07），P = 0.0001）和抑郁症状（B = -0.2（标准误 = 0.10），P = 0.0103）呈负相关。不同时间点，各种应对策略也与这两个基因的位点相关，如自责和物质使用。
我们的研究结果提出了将心理健康症状与DNA甲基化联系起来的有趣假设，有待更大样本进行验证。
