Department of Psychiatry and Psychotherapy, University Hospital, Zurich, Switzerland.
Neuropsychopharmacology. 2012 Jul;37(8):1945-52. doi: 10.1038/npp.2012.41. Epub 2012 Apr 11.
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.
奖赏加工障碍与神经性贪食症（BN）有关。与奖赏相关刺激的处理异常可能与儿茶酚胺能神经递质系统的功能障碍有关，但研究结果尚无定论。研究儿茶酚胺能功能与行为之间关系的一种有力方法是检查对实验性儿茶酚胺耗竭（CD）的行为变化。本研究的目的是在 BN 缓解期受试者中发现潜在的儿茶酚胺能功能障碍，这些受试者在 CD 后进行强化学习任务。通过口服α-甲基-对酪氨酸（AMPT）在 19 名未接受药物治疗的 BN 缓解期（rBN）女性受试者和 28 名人口统计学匹配的健康女性对照者（HC）中实现 CD。假耗竭给予含有苯海拉明的相同胶囊。研究设计包括随机、双盲、安慰剂对照交叉、单站点实验试验。主要观察指标是使用信号检测理论分析概率性奖赏任务中的奖赏学习。次要观察指标包括自我报告评估，包括饮食失调检查问卷。与健康对照组相比，rBN 受试者在 AMPT 条件下而不是在安慰剂条件下表现出奖赏学习迟钝。突出这些发现的特异性，组间在感知区分刺激的能力上没有差异。增加 CD 诱导的快感缺失（但不是饮食失调）症状与对更频繁奖励刺激的反应偏差减小有关。结论，在 CD 下，rBN 受试者与健康对照组相比，奖赏学习能力下降。这些缺陷揭示了 rBN 中与改变的大脑儿茶酚胺水平相关的中枢奖赏加工系统的紊乱，这可能反映出一种与特质相关的缺陷，增加了对 BN 的易感性。
