Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, United Kingdom.
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, United Kingdom.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Nov;8(11):1124-1134. doi: 10.1016/j.bpsc.2023.03.014. Epub 2023 Apr 23.
Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown.
We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT receptor agonist) and 25 received placebo in a randomized double-blind design.
Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions.
Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT receptor agonists in humans and supports the potential for 5-HT receptor agonists to be used in clinical psychiatric populations.
认知缺陷常与心境障碍共病，并可能导致严重的功能障碍，即使主要的心境症状得到缓解。我们目前还没有药物治疗能充分解决这些缺陷。5-羟色胺受体激动剂在动物和早期人类转化研究中显示出作为潜在认知增强剂的希望。人类的最佳认知表现与特定静息状态神经网络之间的适当功能连接直接相关。然而，到目前为止，5-羟色胺受体激动作用对人类大脑静息状态功能连接（rsFC）的影响尚不清楚。
我们收集了 50 名健康志愿者的静息态功能磁共振成像扫描数据，其中 25 名志愿者接受了 6 天×1mg 普拉克索（一种高度选择性的 5-羟色胺受体激动剂）治疗，25 名志愿者接受了安慰剂治疗，采用随机双盲设计。
网络分析确定，普拉克索组的参与者在中央执行网络和后/前扣带皮层之间的 rsFC 增强。种子分析还显示，左侧和右侧额前扣带皮层与左侧外侧枕叶皮层之间的 rsFC 增加，而海马体与默认模式网络区域之间的 rsFC 减少。
与其他潜在的认知增强药物类似，健康志愿者中低剂量的普拉克索似乎增强了认知网络中参与的区域之间的 rsFC，并减少了默认模式网络内的 rsFC。这表明 5-羟色胺受体激动剂在人类中先前观察到的行为认知增强的一种机制，并支持 5-羟色胺受体激动剂在临床精神科人群中的应用潜力。
