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Psilocybin induces time-dependent changes in global functional connectivity
Biological Psychiatry ( IF 10.6 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.biopsych.2019.12.027 Katrin H Preller 1 , Patricia Duerler 2 , Joshua B Burt 3 , Jie Lisa Ji 4 , Brendan Adkinson 4 , Philipp Stämpfli 5 , Erich Seifritz 5 , Grega Repovš 6 , John H Krystal 4 , John D Murray 7 , Alan Anticevic 4 , Franz X Vollenweider 2
Biological Psychiatry ( IF 10.6 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.biopsych.2019.12.027 Katrin H Preller 1 , Patricia Duerler 2 , Joshua B Burt 3 , Jie Lisa Ji 4 , Brendan Adkinson 4 , Philipp Stämpfli 5 , Erich Seifritz 5 , Grega Repovš 6 , John H Krystal 4 , John D Murray 7 , Alan Anticevic 4 , Franz X Vollenweider 2
Affiliation
BACKGROUND
The use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans. METHODS
We conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps. RESULTS
Psilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT2A (5-hydroxytryptamine 2A) and 5-HT1A (5-hydroxytryptamine 1A) receptors. CONCLUSIONS
These results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.
中文翻译:
裸盖菇素诱导全局功能连接的时间依赖性变化
背景裸盖菇素在科学和实验性临床环境中的使用引发了人们对迷幻剂作用机制的新兴趣。然而,其时间依赖性系统级神经生物学在人类中的研究仍然很少。方法 我们进行了一项双盲、随机、平衡、交叉研究,包括 23 名健康人类参与者,他们在 2 个不同的测试日口服安慰剂和 0.2 mg/kg 裸盖菇素。参与者在给药和达到峰值效应之间的 3 个时间点接受磁共振成像:给药后 20 分钟、40 分钟和 70 分钟。通过数据驱动的全局大脑连接方法量化静息状态功能连接,并与皮质基因表达图进行比较。结果 裸盖菇素减少了联想,但同时增加了感觉,全脑连接。这种模式随着时间的推移从给药到达到峰值效应出现。此外,我们发现基线连通性与裸盖菇素诱导的功能连通性变化的程度有关。最后,裸盖菇素诱导的变化与 5-HT2A(5-羟色胺 2A)和 5-HT1A(5-羟色胺 1A)受体的空间基因表达模式呈时间依赖性相关。结论 这些结果表明,感觉区域功能连接的整合和联想区域的解体可能是迷幻状态的基础,并指出了 5-羟色胺 2A 和 1A 受体系统的关键作用。此外,
更新日期:2020-07-01
中文翻译:
裸盖菇素诱导全局功能连接的时间依赖性变化
背景裸盖菇素在科学和实验性临床环境中的使用引发了人们对迷幻剂作用机制的新兴趣。然而,其时间依赖性系统级神经生物学在人类中的研究仍然很少。方法 我们进行了一项双盲、随机、平衡、交叉研究,包括 23 名健康人类参与者,他们在 2 个不同的测试日口服安慰剂和 0.2 mg/kg 裸盖菇素。参与者在给药和达到峰值效应之间的 3 个时间点接受磁共振成像:给药后 20 分钟、40 分钟和 70 分钟。通过数据驱动的全局大脑连接方法量化静息状态功能连接,并与皮质基因表达图进行比较。结果 裸盖菇素减少了联想,但同时增加了感觉,全脑连接。这种模式随着时间的推移从给药到达到峰值效应出现。此外,我们发现基线连通性与裸盖菇素诱导的功能连通性变化的程度有关。最后,裸盖菇素诱导的变化与 5-HT2A(5-羟色胺 2A)和 5-HT1A(5-羟色胺 1A)受体的空间基因表达模式呈时间依赖性相关。结论 这些结果表明,感觉区域功能连接的整合和联想区域的解体可能是迷幻状态的基础,并指出了 5-羟色胺 2A 和 1A 受体系统的关键作用。此外,