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.