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

Abstract

Aim: 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. Methods: 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. Results: 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. Conclusion: Our findings generate intriguing hypotheses linking mental health symptoms and DNA methylation, to be replicated with larger samples.