2026-06-12 バーミンガム大学
＜関連情報＞
- https://www.birmingham.ac.uk/news/2026/laxative-drug-could-improve-depression-related-memory-and-attention-issues
- https://www.cambridge.org/core/journals/psychological-medicine/article/procognitive-effects-of-5ht4-receptor-agonism-in-individuals-with-remitted-depression/EE5A729AD6632A6ED97AC24C8F17DCCB
寛解期うつ病患者における5-HT4受容体作動薬の認知機能促進効果 Pro-cognitive effects of 5-HT4 receptor agonism in individuals with remitted depression
Angharad N. de Cates,Sorcha Hamilton,Anutra Guru,Merethe Blandhol,Michael Colwell,Philip J. Cowen,Meghan Simmons,Bailey Jones,Catherine J. Harmer and Susannah E. Murphy
Phycological Medicine Published:15 June 2026
DOI:https://doi.org/10.1017/S0033291726104450
Abstract
Background
Cognitive impairment is a common and persistent feature of depression, yet it remains poorly understood and inadequately treated. Preclinical and human studies suggest that stimulating 5-HT4 receptors (5-HT4R) enhances neuroplasticity and improves cognition. This novel study examines the cognitive effects of 5-HT4R agonism in adults with a history of recurrent depression.
Methods
Fifty participants who were not currently depressed but had experienced at least two previous episodes of depression were randomized in a double-blind design either to prucalopride (2 mg daily, titrated from 1 mg) or to placebo for 7–10 days. Participants completed self-report questionnaires and a task battery at baseline and post-intervention assessing declarative memory, working memory, emotional processing, and executive function.
Results
Compared to placebo, prucalopride significantly improved word recall on an auditory verbal learning task and was associated with faster response times on a complex working memory task without loss of accuracy. It also improved the accurate recognition of rapidly presented facial expressions. Composite analysis of non-emotional tasks identified that the prucalopride group participants post-intervention were faster and more accurate than at baseline compared to those receiving placebo. Prucalopride had minimal effects on affective cognition, consistent with previous findings. Cognitive improvements were independent of baseline mood symptoms or self-reported cognitive difficulties.
Conclusions
Short-term 5-HT4R agonism improved performance on multiple objective cognitive measures in individuals with remitted depression. These findings replicate our previous results in healthy volunteers showing a pro-cognitive effect of prucalopride and support a role for 5-HT4Rs as a promising target for cognitive enhancement in mood disorders.
