健康志愿者中慢性依地普仑对强化敏感性有特定影响:一项双盲、安慰剂对照半随机研究。

Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study.

机构信息

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.

出版信息

Neuropsychopharmacology. 2023 Mar;48(4):664-670. doi: 10.1038/s41386-022-01523-x. Epub 2023 Jan 23.

Abstract

Several studies of the effects on cognition of selective serotonin reuptake inhibitors (SSRI), administered either acutely or sub-chronically in healthy volunteers, have found changes in learning and reinforcement outcomes. In contrast, to our knowledge, there have been no studies of chronic effects of escitalopram on cognition in healthy volunteers. This is important in view of its clinical use in major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). Consequently, we aimed to investigate the chronic effect of the SSRI, escitalopram, on measures of 'cold' cognition (including inhibition, cognitive flexibility, memory) and 'hot cognition' including decision-making and particularly reinforcement learning. The study, conducted at the University of Copenhagen between May 2020 and October 2021, used a double-blind placebo-controlled design with 66 healthy volunteers, semi-randomised to receive either 20 mg of escitalopram (n = 32) or placebo (n = 34), balanced for age, sex and intelligence quotient (IQ) for at least 21 days. Questionnaires, neuropsychological tests and serum escitalopram measures were taken. We analysed group differences on the cognitive measures using linear regression models as well as innovative hierarchical Bayesian modelling of the Probabilistic Reversal Learning (PRL) task. The novel and important finding was that escitalopram reduced reinforcement sensitivity compared to placebo on both the Sequential Model-Based/Model-Free task and the PRL task. We found no other significant group differences on 'cold' or 'hot' cognition. These findings demonstrate that serotonin reuptake inhibition is involved in reinforcement learning in healthy individuals. Lower reinforcement sensitivity in response to chronic SSRI administration may reflect the 'blunting' effect often reported by patients with MDD treated with SSRIs. Trial Registration: NCT04239339 .

摘要

几项关于选择性 5-羟色胺再摄取抑制剂(SSRIs)对认知影响的研究,无论是在健康志愿者中急性给药还是亚慢性给药,都发现了学习和强化结果的变化。相比之下,据我们所知,尚无关于健康志愿者中 escitalopram 对认知的慢性影响的研究。鉴于其在重度抑郁症(MDD)和强迫症(OCD)中的临床应用,这一点很重要。因此,我们旨在研究 SSRI 依地普仑对“冷”认知(包括抑制、认知灵活性、记忆)和“热”认知(包括决策,特别是强化学习)的慢性影响。该研究于 2020 年 5 月至 2021 年 10 月在哥本哈根大学进行,采用双盲安慰剂对照设计,共有 66 名健康志愿者参与,按年龄、性别和智商(IQ)进行半随机分组,至少接受 20 毫克依地普仑(n = 32)或安慰剂(n = 34)治疗 21 天以上。使用问卷、神经心理学测试和血清依地普仑测量进行研究。我们使用线性回归模型分析了认知测量组间差异,以及概率反转学习(PRL)任务的创新分层贝叶斯建模。新的和重要的发现是,依地普仑与安慰剂相比,在顺序基于模型/无模型任务和 PRL 任务上均降低了强化敏感性。我们没有发现“冷”或“热”认知方面的其他显著组间差异。这些发现表明,血清素再摄取抑制参与了健康个体的强化学习。慢性 SSRI 给药后强化敏感性降低可能反映了接受 SSRIs 治疗的 MDD 患者常报告的“钝化”效应。试验注册:NCT04239339 。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a067/9938113/443ead82741a/41386_2022_1523_Fig1_HTML.jpg

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