Here, using a cohort spanning the entire adult age range (16–96 years old), we extend these prior findings by reporting a robust and highly significant age-associate decrease in FREM3 expression in Brodmann areas 11 and 47—regions broadly overlapping with the orbitofrontal cortex (OFC) as well as the ventrolateral prefrontal cortex (vlPFC), both of which have previously been implicated in depression pathophysiology and risk (Rogers et al., 2004; Stuhrmann et al., 2011). This evidence concerns the gene FREM3 and major depressive disorder.