DNA methylation links between depression and immunity

DNA methylation is a reversible epigenetic mechanism of transcriptional regulation. Changes in DNA methylation patterns are influenced by internal and external factors, and have been associated with various human diseases. We hypothesized that specific methylation changes occur in depressed individuals, and that these changes are associated with disease progression and responses to pharmacological treatments. To test our hypothesis, we analyzed DNA methylation-wide changes in the BiDirect Study's depression and control cohorts. Over the course of two consecutive follow-up visits in 3-year intervals from baseline (i.e. 3 and 6 years after initial assessment), we identified a set of changes in methylation sites within gene enhancer and promoter regions that consistently changed only in depression patients or only in control individuals, respectively. Longitudinal changes in these methylation sites correlated with changes in circulating markers of inflammation and were enriched in biological processes related to innate and adaptive immunity. Currently, we are starting to explore the translational value of these findings by investigating their relationships with depressive symptoms and immunity. Moreover, by applying different machine learning algorithms, we test the utility of a prioritized subset of the identified methylation sites to predict disease status, disease progression, chronic inflammation status and antidepressant response. Overall, we expect to leverage longitudinal DNA methylation information to gain insights into the role of immunity in depression and generate computational tools with potential applications in the clinic.