Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa

Neuropsychopharmacology. 2012 Jul;37(8):1945-52. doi: 10.1038/npp.2012.41. Epub 2012 Apr 11.

Abstract

Disturbances in reward processing have been implicated in bulimia nervosa (BN). Abnormalities in processing reward-related stimuli might be linked to dysfunctions of the catecholaminergic neurotransmitter system, but findings have been inconclusive. A powerful way to investigate the relationship between catecholaminergic function and behavior is to examine behavioral changes in response to experimental catecholamine depletion (CD). The purpose of this study was to uncover putative catecholaminergic dysfunction in remitted subjects with BN who performed a reinforcement-learning task after CD. CD was achieved by oral alpha-methyl-para-tyrosine (AMPT) in 19 unmedicated female subjects with remitted BN (rBN) and 28 demographically matched healthy female controls (HC). Sham depletion administered identical capsules containing diphenhydramine. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were reward learning in a probabilistic reward task analyzed using signal-detection theory. Secondary outcome measures included self-report assessments, including the Eating Disorder Examination-Questionnaire. Relative to healthy controls, rBN subjects were characterized by blunted reward learning in the AMPT--but not in placebo--condition. Highlighting the specificity of these findings, groups did not differ in their ability to perceptually distinguish between stimuli. Increased CD-induced anhedonic (but not eating disorder) symptoms were associated with a reduced response bias toward a more frequently rewarded stimulus. In conclusion, under CD, rBN subjects showed reduced reward learning compared with healthy control subjects. These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bulimia Nervosa / blood
  • Bulimia Nervosa / metabolism*
  • Bulimia Nervosa / psychology*
  • Catecholamines / deficiency*
  • Conditioning, Operant / drug effects
  • Discrimination, Psychological / drug effects
  • Dopamine / deficiency*
  • Double-Blind Method
  • Female
  • Humans
  • Prolactin / blood
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Psychomotor Performance / drug effects
  • Reaction Time / drug effects
  • Reward*
  • alpha-Methyltyrosine / pharmacology*

Substances

  • Catecholamines
  • alpha-Methyltyrosine
  • Prolactin
  • Dopamine