Epigenetic changes may play a role in the increased risk of depression associated with childhood trauma. In this first human trial of epigenetic treatment, we investigated the methyl donor S-adenosylmethionine (SAMe) as add-on to trauma-focused therapy in depression treatment.

This randomized, double-blind, placebo-controlled trial with 6-month follow-up, enrolled 31 adults with depression and a history of childhood trauma. Participants received 1200 mg SAMe or placebo alongside 12 weeks of trauma-focused therapy. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Depression symptoms were assessed using the Hamilton Rating Scale of Depression (HAM-D) and Montgomery-Åsberg Depression Rating Scale (MADRS). Plasma SAMe levels and genome-wide DNA methylation were measured pre- and post-treatment. Non-parametric tests assessed group differences, and we used longitudinal regression models to identify differentially methylated probes and regions.