Neural correlates of weight gain with olanzapine.

CONTEXT Iatrogenic obesity caused by atypical antipsychotics increases the rate of death from all causes. Olanzapine is a commonly prescribed atypical antipsychotic medication that frequently causes weight gain. To our knowledge, the neural correlates of this weight gain have not been adequately studied in humans. OBJECTIVE To test the hypothesis that olanzapine treatment disrupts the neural activity associated with the anticipation and receipt (consumption) of food rewards (chocolate milk and tomato juice). DESIGN Event-related functional magnetic resonance imaging study, before and after a 1-week treatment with olanzapine. SETTING A university neuroimaging center. PARTICIPANTS Twenty-five healthy individuals. MAIN OUTCOME MEASURES Changes in blood oxygen level-dependent activations to the anticipation and receipt of food rewards after olanzapine treatment. RESULTS One week of olanzapine treatment caused significant increases in weight, food consumption, and disinhibited eating. Our imaging data showed enhanced activations in the inferior frontal cortex, striatum, and anterior cingulate cortex to the anticipation of a food reward. Activation in the caudate and putamen were enhanced to the receipt of the rewarding food. We also found a decrease in reward responsivity to receipt of the rewarding food in the lateral orbital frontal cortex, an area of the brain thought to exercise inhibitory control on feeding. CONCLUSIONS Olanzapine treatment enhanced both the anticipatory and consummatory reward responses to food rewards in the brain reward circuitry that is known to respond to food rewards in healthy individuals. We also noted a decrease in responsivity to food consumption in a brain area thought to inhibit feeding behavior.