(PS5-B33) Intermittent Theta-burst Transcranial Magnetic Stimulation for Post-traumatic Stress Disorder: The Role of Epigenetic Mediation

Author List: Quinn, M.J., McGeary, J.E., Starr, C.N., Borgia, M., Bachman, C.E., Catalano, J.L. & Philip, N.S.

Neurostimulation is an increasingly utilized treatment for a range of psychiatric disorders. In Veterans with Post Traumatic Stress Disorder (PTSD), intermittent theta burst transcranial magnetic stimulation (iTBS) demonstrated clinically meaningful symptom reduction following a double-blind sham control trial conducted by Philip et al. (2019). Despite rising evidence for the efficacy of neurostimulation, treatment response varies across individuals, suggesting inter-individual predictors. Genetic and epigenetic mechanisms may operate as useful biomarkers to predict treatment response following iTBS. To explore how epigenetic influences, specifically DNA methylation, relate to iTBS outcomes, DNA samples were obtained from a sub-set (n=23) of participants enrolled in Philip et al. (2019) at baseline and end of two-week treatment phase. Polymerase chain reaction (PCR) pyrosequencing produced average percent change in methylation across multiple CpG sites on the COMT and BDNF genes respectively. Linear regression analyses revealed that average BDNF methylation did not significantly predict iTBS treatment response. However, when controlling for epigenetic influences, significant main effects of both treatment group (β= -23.29, p=0.01) and average COMT methylation (β = -2.11, p=0.02) on PTSD symptomology were found. Interestingly, a cross-over interaction emerged such that for participants receiving active iTBS, greater COMT genetic expression was related to an attenuated reduction in PTSD symptoms compared to those with lower COMT gene expression (β =2.93, p=0.01). Taken together, these results suggest that epigenetic mediation, particularly COMT methylation, could serve as a biological predictor of iTBS treatment response. Further study of the interplay between neurostimulation and epigenetic mechanisms may open the door for adjunctive interventions to bolster treatment outcomes. An examination of epigenetic mediation of iTBS administered in conjunction with cognitive behavioral therapy is also warranted to determine the potential efficacy of combined treatment for psychiatric disorders.