NIHR Oxford Health Biomedical Research Centre, Warneford Hospital, Oxford OX3 7JX, UK
Psychopharmacology and Emotion Research Laboratory, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK.
Philos Trans R Soc Lond B Biol Sci. 2018 Mar 19;373(1742). doi: 10.1098/rstb.2017.0030.
Antidepressants remediate negative biases in emotional processing early in treatment, prior to mood improvement. However, the effects on reward processing potentially relevant to the treatment of anhedonia are less clear. Here we investigate the early and sustained effects of the dopamine and noradrenaline reuptake inhibitor bupropion on behavioural measures of emotional and reward processing in currently depressed individuals. Forty-six currently depressed patients and 42 healthy controls participated in a repeated measures study, during which open-label bupropion was administered to only the patient group over a six week period without a placebo group. All participants completed the Emotional Test Battery and a probabilistic instrumental learning task at week 0, week 2 and week 6. Currently depressed patients displayed negative biases in emotional processing and blunted response bias for high-probability wins compared to the healthy controls at baseline. Bupropion was found to reduce the negative biases in emotional processing early in treatment, including a significant decrease in the percentage misclassification of other face emotions as sad and the number of negative self-referent words falsely recalled between baseline and week 2. Conversely, bupropion was found to initially further reduce the response bias for high-probability wins between baseline and week 2. This effect reversed with six weeks' bupropion treatment and reward processing was normalized compared to the healthy controls. Early in treatment, bupropion acts to reduce negative biases in emotional processing but exacerbates impaired reward processing. The beneficial actions of bupropion on reward processing then occur later in treatment. Such dissociation in the temporal effects of bupropion on emotional and reward processing has implications for the treatment of the different symptom domains of negative affect and anhedonia in depression.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.
抗抑郁药可在治疗早期（情绪改善之前）纠正情绪处理中的负性偏差。然而，其对奖赏处理的影响（与治疗快感缺失相关）尚不明确。在此，我们研究了多巴胺和去甲肾上腺素再摄取抑制剂安非他酮对当前抑郁患者情绪和奖赏处理的行为测量的早期和持续影响。46 名当前抑郁患者和 42 名健康对照者参与了一项重复测量研究，在此期间，仅患者组接受了为期六周的安非他酮开放标签治疗，而无安慰剂组。所有参与者在第 0、2 和 6 周完成了情绪测试电池和概率性工具学习任务。与健康对照组相比，当前抑郁患者在基线时表现出情绪处理中的负性偏差和对高概率获胜的反应偏差减弱。研究发现，安非他酮在治疗早期可减少情绪处理中的负性偏差，包括在将其他面孔情绪错误分类为悲伤和错误回忆的负性自我参照词的数量方面，从基线到第 2 周显著减少。相反，研究发现，安非他酮在从基线到第 2 周之间，最初进一步降低了对高概率获胜的反应偏差。这种效应在 6 周的安非他酮治疗后发生逆转，与健康对照组相比，奖赏处理正常化。在治疗早期，安非他酮作用是减少情绪处理中的负性偏差，但会加剧受损的奖赏处理。安非他酮对奖赏处理的有益作用随后在治疗后期出现。安非他酮对情绪和奖赏处理的时间效应的这种分离，对治疗抑郁中的不同负性情绪和快感缺失症状领域具有意义。本文是一次讨论会议的一部分，主题为“老鼠与心理健康：促进基础和临床神经科学家之间的对话”。
