Original Article

Neuropsychopharmacology (2012) 37, 2031–2046; doi:10.1038/npp.2012.51; published online 2 May 2012

Anorexia Nervosa and Obesity are Associated with Opposite Brain Reward Response

Guido K W Frank1,2, Jeremy R Reynolds3, Megan E Shott1, Leah Jappe4, Tony T Yang5, Jason R Tregellas1,2 and Randall C O'Reilly6

  1. 1Department of Psychiatry, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
  2. 2Department of Neuroscience, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
  3. 3Department of Psychology, University of Denver, Denver, CO, USA
  4. 4Department of Psychology, University of Minnesota, Minneapolis, MN, USA
  5. 5Department of Psychiatry, University of California San Diego, San Diego, CA, USA
  6. 6Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA

Correspondence: Dr GKW Frank, The Children's Hospital, Gary Pavilion A036/B-130, 13123 East 16th Avenue, Aurora, CO 80045, USA, Tel: +1 720 777 1909, Fax: +1 720 777 7306, E-mail: Guido.Frank@ucdenver.edu

Received 15 November 2011; Revised 15 March 2012; Accepted 16 March 2012
Advance online publication 2 May 2012



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.


anorexia nervosa; obesity; fMRI; dopamine; reward; brain activation

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