A Neural Circuitry Linking Insulin Resistance to Depressed Mood

OBJECTIVE: Insulin resistance (IR) confers risk for Type 2 diabetes and is associated with depressed mood. Neurons within the ventral striatum (VS) are sensitive to insulin levels and show altered function in the context of both IR and depression. Hence, VS may represent a critical component of a neural circuitry linking IR to depressed mood. METHODS: Ninety adults (aged 30-50 years) free from major psychiatric illnesses and diabetes participated. Fasting blood was sampled, and participants completed a set of questionnaires (including the Beck Depression Inventory-II). Participants also underwent resting-state functional magnetic resonance imaging of the brain. Seed-based connectivity analyses, centered on VS, were conducted to examine how resting-state interregional connectivity patterns covaried with IR and depressed mood. RESULTS: Higher levels of IR covaried with increased connective strength between the left VS and two regions: the insula and the anterior midcingulate cortex (aMCC). Moreover, aMCC-VS connectivity predicted depressed mood (b = 0.93, standard error = 0.36, F(change)(1,81) = 6.54, p = .01). Finally, aMCC-VS connectivity was shown by Monte Carlo analysis to mediate the relationship between IR and depressed mood (a*b indirect effect = 0.16, confidence interval = 0.005-0.39, p = .03). CONCLUSIONS: IR relates to changes in the functional connectivity between VS and aMCC. These changes in interregional communication partly account for the coupling of IR to depressed mood in otherwise healthy adults. These findings are relevant for understanding bidirectional associations between diabetes risk and depressed mood.