Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B=−173.40, t=−2.324, p-value=0.023).

Background
Consequences of war-related traumatisation have mostly been investigated in military and predominant male populations, while research on female civilian victims of war has been neglected. Furthermore, research of post-war posttraumatic stress disorder (PTSD) in women has rarely included early-life trauma in their prediction models, so the contribution of trauma in childhood and early youth is still unexplored.
Objective

Nightmares are a common problem with debilitating consequences. Meta-analyses have revealed that imagery rehearsal therapy (IRT), in which the storyline of the recurring nightmare is changed, is the treatment of choice for nightmares. In a randomized clinical trial, we recently demonstrated that IRT was also effective in a population of patients with diverse psychiatric disorders. In this trial, IRT showed moderate additional benefits over treatment as usual on nightmare distress, general psychopathology, and posttraumatic stress symptoms.

DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10(-6)). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation).