The means by which social environmental exposures influence risk of mental disorders is a persistent and still open question. A key candidate mechanism for the biologic mediation of environmental effects involves epigenetic factors, which regulate gene function without altering underlying DNA sequence. Recent work has shown that environmental exposures such as childhood abuse, family history of mental disorder, and low socioeconomic status (SES) associate with differential DNA methylation (5mC) – a relatively stable, but modifiable, epigenetic factor. However, the longitudinal relation (...) among SES, 5mC, brain function, and risk of depression remains to be elucidated. Here, we briefly review literature relevant to these associations and discuss recent findings that, for the first time, prospectively demonstrate sequential links between low SES, changes in 5mC, changes in brain function, and risk of depression in a cohort of adolescents. (shrink)