Epigenetics in persons living with HIV: trauma, coping, and FKBP5 and SLC6A4 methylation

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 (n = 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), p = 0.0109), depression (B = −0.06 (SE = 0.03), p = 0.0435), and PTSD symptoms at baseline (B = −0.03 (SE = 0.01), p = 0.0374). DNAm at FKBP5 was negatively associated with measures of anxiety (B = −0.30 (SE = 0.07), p = 0.0001) and depression symptoms (B = −0.2 (SE = 0.10), p = 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. Many people living with HIV experience high levels of trauma and mental health difficulties in their lifetime. One way in which this trauma may affect mental health, is through a process called epigenetics, in which chemical changes are made to the DNA in response to different exposures. Small chemical groups called methyl groups are placed onto a cytosine (the C in our DNA), which can modify how available the DNA is to be expressed into a protein. These methylation patterns at stress-related genes can essentially tune up or down a body’s response to a stressor. In our study, we examined how these methylation differences at important regulatory locations in stress-related genes may be related to exposure to lifetime histories of trauma, as well as symptoms of depression, anxiety, and perceived stress, and various coping strategies people use to deal with trauma or stress, such as humor, denial, self-blame, or substance use. We found that higher DNA methylation levels at multiple positions in the two studied genes were related to lower levels of symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD) in a population of adults living with HIV. Some of the coping strategies, such as self-blame and substance use, were also related to DNA methylation at both studied genes. These findings indicate that epigenetic differences may contribute to mental health symptoms in people with HIV.