Association of Insulin Resistance With Depression Severity and Remission Status: Defining a Metabolic Endophenotype of Depression

Insulin resistance (IR) is a physiological state characterized by the attenuated response of peripheral receptors to insulin.1 It is a known risk factor for somatic and brain-based disorders, including cardiovascular disease, Alzheimer disease, and major depressive disorder (MDD).1,2 Several plausible mechanisms tie IR to MDD.3 Insulin resistance leads to diminished insulin-mediated glucose disposal, compensatory hyperinsulinemia, and type 2 diabetes.1,2 However, there is little evaluation of how IR is associated with specific features of major depression. Characterization of these associations represents a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD. We investigated whether IR was positively associated with the presence of major depression, the severity of major depression, and the chronicity of major depression using the Netherlands Study of Depression and Anxiety (NESDA).