The following is a summary of “Sex-dependent association of DNA methylation of HPA axis-related gene FKBP5 with obsessive-compulsive disorder,” published in the December 2023  issue of Psychiatry by Seo, et al.

The hypothalamic-pituitary-adrenal (HPA) axis does not work properly in people with obsessive-compulsive disorder (OCD). However, epigenetic changes in genes linked to the HPA axis have not been well studied in OCD. For a study, researchers sought to determine whether the epigenetic control of the FKBP5 gene intron 7 was linked to OCD in both males and females. They also looked into the connections between the DNA methylation levels of FKBP5 intron 7, having OCD, and having been abused as a child.

267 people with OCD and 201 healthy people between 18 and 40 were asked to participate. They did a clinical and demographic study, genotyping of FKBP5 rs1360780, and pyrosequencing of FKBP5 intron 7. DNA was taken from leucocytes in the peripheral blood.  To begin, they did a multivariate analysis of covariance for differences in DNA methylation levels between people with OCD and healthy controls. They took into account the FKBP5 rs1360780 gene, traumatic events in early life, depressed symptoms, and age as factors for both men and women. Next, path analysis was used to find out how DNA methylation levels of FKBP5 affected the link between a traumatic event in early childhood and an OCD state. Also, additional studies were done for both medicine and overall major depression. DNA methylation at the FKBP5 intron 7 CpG site was much lower in men with OCD than healthy men (mean difference −1.33%, 95% CI −2.11 to −0.55, P < 0.001). 

The results were still important for people who had never used drugs or were drug-free (mean difference −1.27%, 95% CI −2.18 to −0.37, P = 0.006, in men) and for people who had never had a major depressive disorder in their lives (mean difference −1.60%, 95% CI −2.54 to −0.66, P < 0.001, in men). There was no major link between early-life stress and OCD state through DNA methylation levels.  The results showed that epigenetic factors of the HPA axis-related gene FKBP5 may help explain how OCD starts. More research was needed to find out how changes in the methylation of FKBP5 intron 7 and the function of the HPA axis are connected to OCD.

Source: sciencedirect.com/science/article/abs/pii/S0306453023003827