Anorexia nervosa and obesity are associated with opposite brain reward response

Abstract

Anorexia nervosa (AN) is a severe psychiatric disorder associated with food avoidance and malnutrition. In this study, we wanted to test whether we would find brain reward alterations in AN, compared with individuals with normal or increased body weight. We studied 21 underweight, restricting-type AN (age M 22.5, SD 5.8 years), 19 obese (age M 27.1, SD 6.7 years), and 23 healthy control women (age M 24.8, SD 5.6 years), using blood oxygen level-dependent functional magnetic resonance brain imaging together with a reward-conditioning task. This paradigm involves learning the association between conditioned visual stimuli and unconditioned taste stimuli, as well as the unexpected violation of those learned associations. The task has been associated with activation of brain dopamine reward circuits, and it allows the comparison of actual brain response with expected brain activation based on established neuronal models. A group-by-task condition analysis (family-wise-error-corrected P<0.05) indicated that the orbitofrontal cortex differentiated all three groups. The dopamine model reward-learning signal distinguished groups in the anteroventral striatum, insula, and prefrontal cortex (P<0.001, 25 voxel cluster threshold), with brain responses that were greater in the AN group, but lesser in the obese group, compared with controls. These results suggest that brain reward circuits are more responsive to food stimuli in AN, but less responsive in obese women. The mechanism for this association is uncertain, but these brain reward response patterns could be biomarkers for the respective weight state.

Figure 1

The group-by-condition analysis indicated significant group differences in the lateral orbitofrontal cortex (OFC), as well as the putamen and anteroventral striatum; brain maps family-wise error (FWE)-corrected P<0.05, cluster threshold ⩾5 voxels. Beta value bar graphs indicated increased OFC response to unexpected reward receipt in anorexia nervosa (AN) compared with controls (CW), but a reduced response in obese women (OB) compared with CW; anteroventral striatum response was reduced in OB compared with CW and AN groups (Dunnett's T3, ^*P<0.05, ^**P<0.01, ^***P<0.001).

Figure 2

Computational model group comparison (analysis of covariance) indicating greater brain response across groups in the anteroventral striatum, insula, and dorsolateral frontal cortex (P<0.001 uncorrected, cluster threshold ⩾25 voxels). The extracted parameter estimates for those regions were greater in anorexia nervosa (AN) compared with control (CW), but reduced in obese women (OB; Dunnett's T3, ^*P<0.05, ^**P<0.01, ^***P<0.001).