Dopamine-Related Deficit in Reward Learning After Catecholamine Depletion in Unmedicated, Remitted Subjects with Bulimia Nervosa

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 AMPTFbut not in placeboFcondition. 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.

Well-Being: An Important Concept for Psychotherapy and Psychiatric Neuroscience

“…Conceivably, this impairment contributes to a lack of planfulness and positive health, and therefore increases the risk of relapse. In asymptomatic ex-bulimic women, we showed marked deficits in reward learning [23]. Following Seneca's suggestion that psychological well-being is primarily a learning process, it is plausible to relate this deficit to long-lasting reductions in quality of life and impaired personal growth, which are frequent problems in individuals recovered from severe psychosomatic illness.…”

Pleasurable music affects reinforcement learning according to the listener

“…Subjectivity seems to have profound effects on dopamine transmission, implying that the discordant conclusions of previous reinforcement learning research could arise from complex interactions between innate predispositions, neuroplastic changes, and experimental manipulations underlying dopamine efficacy. Though there is a growing body of research on the ability of dopaminergic agonists/antagonists to influence instrumental learning in neuropsychiatric disorders (e.g., Frank et al, 2004; Chase et al, 2010; Worbe et al, 2011; Grob et al, 2012), no study that we know of has investigated the relationships between individual factors and dopaminergic manipulations in healthy subjects. We found subjective modulations of music's effects, signifying that our enjoyment of music depends a great deal on the amount of music we listen to, how we listen to it, how we engage with it, our musical experience, and even our reasons for approaching it.…”

Behavioral Responses to Catecholamine Depletion in Unmedicated, Remitted Subjects with Bulimia Nervosa and Healthy Subjects

“…The study protocol was approved by the ethics committee of the Canton Zurich. The sample of this study overlaps with the sample of prior published data (22,23). We used a randomized, doubleblind, placebo-controlled, crossover design in which each subject underwent 2 identical sessions separated by at least 7 days in which they received either AMPT or placebo.…”