Unraveling the heterogeneity of ptsd symptoms through identifying epigenetic subtypes among trauma-exposed civilian women

PTSD is a heterogeneous psychiatric disorder with varying presentations of emotional modulation, symptom trajectories, and functioning. Recent advances in omics research have shed light on the genetic and epigenetic underpinnings of PTSD symptoms. However, little is known about if biologically defined subtypes could be identified using epigenetic data and how they might relate to symptoms and health, particularly among civilian women. Using data from a subsample of the Nurses’ Health Study II (n=707), we performed clustering among trauma exposed women using DNA methylation (DNAm) from two blood collections 11-16 years apart collected after trauma exposure, limited to 8,331 markers associated with lifetime PTSD symptoms measured in 2008 (re-experiencing, hyperarousal, and avoidance) with an FDR Three epigenetic subtypes were identified, which consisted of 352, 228, and 127 participants, respectively. The subtypes showed clear separation in PTSD and depressive symptoms in 2008. They also differed in their epigenetic scores for two proteins, CNTN4 (p=0.009) and NTRK3 (p=0.005): Subtype 1 exhibited the lowest scores and Subtypes 2 and 3 showed comparable levels. Subtype 3 was associated with slightly more lifetime traumatic events experienced and childhood trauma, as well as higher levels of current depressive and PTSD symptoms in 2017 and 2018, compared to the other two subtypes. While Subtype 3 also reported more memory issues and lower life satisfaction, there was no difference in physical functioning or risk factors for physical health (i.e., diet, physical activity, or body mass index). Using epigenetic markers of PTSD symptoms, we identified three subtypes of trauma exposed women, displaying a gradient of symptom severity, trauma burden, and subjective cognitive functioning and life satisfaction in 10 years, but no difference in physical health. Intriguingly, epigenetic scores for two proteins were the lowest in Subtype 1 (moderate symptoms), which could have long-term implications not captured during our follow-up, given that lower epigenetic scores for these proteins associated with heightened disease risks in prior studies. Further analyses are under way to assess clustering robustness and generalizability. Our findings highlight the connections between biological heterogeneity of PTSD and health in middle-aged trauma exposed women.