Following our early postulate that IR is a part of—and may contribute to—the pathophysiology of depression,15, 16 we reported an antidepressant response to an insulin-sensitizing agent, metformin,17 and to the PPAR-γ agonists rosiglitazone18 and Pioglitazone19 in patients with unremitted depression. The gene discussed is PPARG; the disease is major depressive disorder.