Neural Correlates of Weight Gain With Olanzapine

Abstract

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.

Associations Among Obesity, Acute Weight Gain, and Response to Treatment with Olanzapine in Adolescent Schizophrenia

“…Dopamine D1 and D2 receptor antagonism through their impact on the reward system may also play a role, as it has recently been shown there is an increased anticipatory reward responsivity toward food reward in the inferior frontal cortex, striatum, and anterior cingulate cortex during olanzapine treatment (Mathews et al 2012).…”

The role of ghrelin signalling in second-generation antipsychotic-induced weight gain

“…Interestingly, SGAs, including olanzapine, have been suggested to deteriorate the pre-existing hedonic alterations (enhanced anticipation of food reward) in schizophrenia patients (Elman et al, 2006;Mathews et al, 2012). However, to the best of our knowledge, the role of rewarding system through ghrelin signalling in SGA-induced weight gain has not yet been reported.…”

Atypical antipsychotics and effects on feeding: from mice to men

“…•OLA-treated patients gained substantial weight, mediated by an increase in caloric intake (27.7 %) •No change in diet composition, REE, or physical activity Theisen et al (2003) Cross-sectional (Leadbetter et al 1992;Treuer et al 2009), increases in appetite and food intake (Fountaine et al 2010;Gothelf et al 2002;Roerig et al 2005;Mathews et al 2012), and poor dietary choices (McCreadie et al 1998). We review these studies below, according to population (i.e., healthy controls versus patients), AAP, and comparison group (Table 1).…”

“…Thus, AP-naïve individuals or healthy participants, having never been exposed to APs, can be expected to show the greatest susceptibility to metabolic side effects of AAPs and studies using such individuals allow us to evaluate metabolic side effects independent of psychotic illness and previous AP usage. Three studies exist involving OLA given to healthy subjects; all demonstrate increased body weight with associated increases in hunger or feeding (Fountaine et al 2010;Roerig et al 2005;Mathews et al 2012). Roerig et al (2005) demonstrated that 37.5 % of healthy participants given OLA had increased hunger scores measured by a visual analog scale (VAS) accompanied by an average weight gain of 2.25 kg.…”

“…Fountaine et al reported a 23 % increase in 24 h food intake (volunteers were provided standardized menu/snack choices) and an increase in body weight of 2.62 kg (versus 0.08 kg for placebo) over 12 days of OLA treatment (Fountaine et al 2010). Finally, Mathews et al (2012) used fMRI to examine brain activity in healthy individuals given OLA and found enhanced activation of brain areas involved in anticipation and consumption in response to food reward. They also found a decrease in responsivity to food consumption in the brain area involved in feeding inhibition.…”