近日，英国帝国理工学院Richard E. Daws等研究人员发现，赛洛西宾治疗抑郁症后大脑中的全局整合能力增强。这一研究成果于2022年4月11日在线发表在国际学术期刊《自然—医学》上。

研究人员在两项抑郁症的临床试验中评估了赛洛西宾对大脑功能的亚急性影响。第一个是在治疗耐受性抑郁症患者中进行的口服赛洛西宾（10毫克和25毫克，间隔7天）的开放标签试验。功能磁共振成像（fMRI）在基线和25毫克剂量后的1天被记录。Beck's 抑郁症清单是主要的结果测量（MR/J00460X/1）。第二项试验是一项双盲II期随机对照试验，比较了赛洛西宾治疗和艾司西酞普兰。重度抑郁症患者接受了2×25毫克的口服赛洛西宾，间隔3周，加上6周的每日安慰剂（"赛洛西宾组"）或2×1毫克的口服赛洛西宾，间隔3周，加上6周的每日艾司西酞普兰（10-20毫克）（"艾司西酞普兰组"）。在基线和第二次服用赛洛西宾后3周记录fMRI（NCT03429075）。

在这两项试验中，对赛洛西宾的抗抑郁反应是快速、持续的，并与fMRI大脑网络模块化的减少相关，这意味着赛洛西宾的抗抑郁作用可能取决于大脑网络整合的全面增加。网络制图分析表明，富含5-HT2A受体的高阶功能网络在赛洛西宾治疗后变得更有功能上的相互联系和灵活性。艾司西酞普兰的抗抑郁反应比较温和，没有观察到大脑网络组织的变化。在两项研究中，与药效相关的大脑变化与强有力的抗抑郁效果相关，表明赛洛西宾治疗的抗抑郁机制：大脑网络整合的全面增加。

据悉，赛洛西宾治疗显示出抗抑郁的潜力，但它的治疗作用还不太清楚。

附：英文原文

Title: Increased global integration in the brain after psilocybin therapy for depression

Author: Daws, Richard E., Timmermann, Christopher, Giribaldi, Bruna, Sexton, James D., Wall, Matthew B., Erritzoe, David, Roseman, Leor, Nutt, David, Carhart-Harris, Robin

Issue&Volume: 2022-04-11

Abstract: Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10mg and 25mg, 7d apart) in patients with treatment-resistant depression. Functional magnetic resonance imaging (fMRI) was recorded at baseline and 1d after the 25-mg dose. Beck’s depression inventory was the primary outcome measure (MR/J00460X/1). The second trial was a double-blind phase II randomized controlled trial comparing psilocybin therapy with escitalopram. Patients with major depressive disorder received either 2×25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin arm’) or 2×1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10–20mg) (‘escitalopram arm’). fMRI was recorded at baseline and 3 weeks after the second psilocybin dose (NCT03429075). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. The antidepressant response to escitalopram was milder and no changes in brain network organization were observed. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration.

DOI: 10.1038/s41591-022-01744-z

Source: https://www.nature.com/articles/s41591-022-01744-z