Longitudinal study identifies methylation changes during antidepressant treatment

Researchers conducted a secondary analysis of the Early Medication Change trial, examining DNA methylation in 162 patients with major depressive disorder (81 responders and 81 non-responders) and 48 matched healthy controls. Patients received standardized antidepressant treatment and were assessed at four time points over eight weeks; controls were assessed twice. The analyses tested associations between methylation patterns, diagnosis and depressive symptom outcomes.

Baseline methylation in two regions was associated with symptom severity at day 28, and six regions were associated with severity at day 56. No individual methylation site was significant in these baseline analyses. Longitudinal analyses identified one site associated with symptom improvement and three regions with methylation changes over time, including regions near GPR126 and PM20D1. Combined patient-control analyses identified additional methylation associations with diagnosis and temporal effects.

The findings provide longitudinal evidence of peripheral DNA methylation changes associated with antidepressant treatment and response, but do not establish that these changes cause clinical improvement or can predict outcomes in practice. The authors note that replication and functional validation are needed before the results can inform personalized treatment. The study was a secondary analysis and does not compare the efficacy of different antidepressant strategies.