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多巴胺和血清素的强化学习模型能告诉我们关于抗抑郁药作用的哪些信息?

What Can Reinforcement Learning Models of Dopamine and Serotonin Tell Us about the Action of Antidepressants?

作者信息

Lan Denis C L, Browning Michael

机构信息

Department of Experimental Psychology, University of Oxford, Oxford, GB.

Department of Psychiatry, University of Oxford, Oxford, GB.

出版信息

Comput Psychiatr. 2022 Jul 20;6(1):166-188. doi: 10.5334/cpsy.83. eCollection 2022.

Abstract

Although evidence suggests that antidepressants are effective at treating depression, the mechanisms behind antidepressant action remain unclear, especially at the cognitive/computational level. In recent years, reinforcement learning (RL) models have increasingly been used to characterise the roles of neurotransmitters and to probe the computations that might be altered in psychiatric disorders like depression. Hence, RL models might present an opportunity for us to better understand the computational mechanisms underlying antidepressant effects. Moreover, RL models may also help us shed light on how these computations may be implemented in the brain (e.g., in midbrain, striatal, and prefrontal regions) and how these neural mechanisms may be altered in depression and remediated by antidepressant treatments. In this paper, we evaluate the ability of RL models to help us understand the processes underlying antidepressant action. To do this, we review the preclinical literature on the roles of dopamine and serotonin in RL, draw links between these findings and clinical work investigating computations altered in depression, and appraise the evidence linking modification of RL processes to antidepressant function. Overall, while there is no shortage of promising ideas about the computational mechanisms underlying antidepressant effects, there is insufficient evidence directly implicating these mechanisms in the response of depressed patients to antidepressant treatment. Consequently, future studies should investigate these mechanisms in samples of depressed patients and assess whether modifications in RL processes mediate the clinical effect of antidepressant treatments.

摘要

尽管有证据表明抗抑郁药在治疗抑郁症方面有效,但抗抑郁作用背后的机制仍不清楚,尤其是在认知/计算层面。近年来,强化学习(RL)模型越来越多地被用于描述神经递质的作用,并探究在抑郁症等精神疾病中可能发生改变的计算过程。因此,RL模型可能为我们提供一个机会,以更好地理解抗抑郁作用的计算机制。此外,RL模型还可能帮助我们了解这些计算过程在大脑中(例如中脑、纹状体和前额叶区域)是如何实现的,以及这些神经机制在抑郁症中可能如何改变,并通过抗抑郁治疗得到修复。在本文中,我们评估了RL模型帮助我们理解抗抑郁作用潜在过程的能力。为此,我们回顾了关于多巴胺和5-羟色胺在RL中的作用的临床前文献,将这些发现与研究抑郁症中改变的计算过程的临床工作联系起来,并评估将RL过程的改变与抗抑郁功能联系起来的证据。总体而言,虽然关于抗抑郁作用的计算机制不乏有前景的观点,但直接表明这些机制与抑郁症患者对抗抑郁治疗的反应相关的证据并不充分。因此,未来的研究应该在抑郁症患者样本中研究这些机制,并评估RL过程的改变是否介导了抗抑郁治疗的临床效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a8/11104395/837ec6f445e5/cpsy-6-1-83-g1.jpg

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