A mechanistic account of serotonin's impact on mood
A mechanistic account of serotonin's impact on mood
复制标题
DOI：
10.1038/s41467-020-16090-2
复制
发表时间：
2020-05-11
影响因子：
16.6
通讯作者：
Dolan, Raymond J.
中科院分区：
文献类型：
--
作者：
Michely, Jochen;Eldar, Eran;Dolan, Raymond J.
选择性5-羟色胺再摄取抑制剂（SSRIs）构成一线抗抑郁干预，尽管解释治疗反应的精确认知和计算机制仍然难以捉摸。在健康志愿者中使用为期一周的SSRI治疗，我们发现5-羟色胺增强了实验诱导的积极影响对学习新事物的影响，以及对先前学习的奖励关联的重新巩固。计算模型表明，这些影响最好是由学习过程中主观奖励感知的提升来解释的，这是在积极而非消极的情绪诱导之后。因此，SSRIs可能会放大两者之间的相互作用，而不是直接影响情感或奖励敏感性，从而引起延迟的情绪反应。我们认为，这种影响学习动力学的调制可以解释这些药物逐渐改善情绪的演变，并提供了一种新的候选机制，随着时间的推移，展开5-羟色胺的抗抑郁作用。SSRIs抗抑郁治疗反应背后的认知计算机制还不清楚。在这里，作者表明，SSRI治疗健康受试者一周表现为当学习发生在积极的情绪环境中时，对积极结果的感知放大。
Selective serotonin reuptake inhibitors (SSRIs) constitute a first-line antidepressant intervention, though the precise cognitive and computational mechanisms that explain treatment response remain elusive. Using week-long SSRI treatment in healthy volunteer participants, we show serotonin enhances the impact of experimentally induced positive affect on learning of novel, and reconsolidation of previously learned, reward associations. Computational modelling indicated these effects are best accounted for by a boost in subjective reward perception during learning, following a positive, but not negative, mood induction. Thus, instead of influencing affect or reward sensitivity directly, SSRIs might amplify an interaction between the two, giving rise to a delayed mood response. We suggest this modulation of affect-learning dynamics may explain the evolution of a gradual mood improvement seen with these agents and provides a novel candidate mechanism for the unfolding of serotonin's antidepressant effects over time. The cognitive computational mechanisms underlying the antidepressant treatment response of SSRIs is not well understood. Here the authors show that SSRI treatment in healthy subjects for a week manifests as an amplification of the perception of positive outcomes when learning occurs in a positive mood setting.