Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis
Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis
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DOI：
10.1093/schbul/sbs117
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发表时间：
2013-11-01
影响因子：
6.6
通讯作者：
Nutt, David J.
中科院分区：
文献类型：
--
作者：
Carhart-Harris, Robin L.;Leech, Robert;Nutt, David J.
裸盖菇素是一种经典的迷幻药，也是一种精神病的候选药物模型。本研究采用功能磁共振成像技术（fMRI）检测裸盖菇素对静息态网络和丘脑皮层功能连接（FC）的影响。15名健康志愿者在2次无任务静息状态扫描中接受了裸盖菇素和安慰剂的静脉输注。主要分析集中在默认模式（DMN）和任务积极网络（TPN）之间的FC的变化。DMN中的自发活动与TPN中的自发活动是正交的，众所周知，这些网络支持非常不同的功能（即，DMN支持内省，而TPN支持外部集中注意力）。在此，独立组分和基于种子的FC分析显示，裸盖菇素给药后DMN-TPN FC增加，因此DMN-TPN正交性降低。在精神病和冥想状态中发现DMN-TPN FC增加，这与迷幻状态有一些现象学相似之处。在镇静中也观察到DMN-TPN FC增加，丘脑皮质FC减少，但在这里我们发现裸盖菇素后丘脑皮质FC保留。因此，我们建议，丘脑皮质FC可能与唤醒，而DMN-TPN FC是与分离的内部和外部的关注状态。我们认为，这种正交性是妥协的早期精神病，解释其现象学和迷幻状态之间的相似之处，并支持实用的裸盖菇素作为早期精神病的模型。
Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode-(DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.