Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London, W12 0NN, London, UK.
Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Department of Medicine, Imperial College London, W12 0NN, London, UK.
Sci Rep. 2017 Oct 13;7(1):13187. doi: 10.1038/s41598-017-13282-7.
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.
在精神病学中，有心理支持的迷幻蘑菇显示出作为一种治疗模式的前景，但它的治疗机制还了解甚少。在这里，我们使用功能磁共振成像（fMRI）测量了接受迷幻蘑菇（血清素激动剂）治疗难治性抑郁症（TRD）前后的大脑血流（CBF）和血氧水平依赖（BOLD）静息状态功能连接（RSFC）。从 19 名患者中收集了 16 名患者治疗前后质量合格的 fMRI 数据。在治疗后 1 周，所有 19 名患者的抑郁症状均有所改善，47%的患者在 5 周时符合反应标准。全脑分析显示，治疗后颞叶皮层（包括杏仁核）的 CBF 下降。杏仁核 CBF 的减少与抑郁症状的减轻相关。在针对 RSFC 分析的预先选择的电路的重点上，治疗后观察到默认模式网络（DMN）内的 RSFC 增加。腹内侧前额叶皮层-双侧下外侧顶叶皮层 RSFC 的增加与 5 周时的治疗反应相关，而海马旁回-前额叶皮层 RSFC 的减少也是如此。这些数据填补了迷幻蘑菇治疗后大脑影响的重要知识空白，也是抑郁症患者中的首例。治疗后的大脑变化与以前观察到的迷幻蘑菇和其他“迷幻药”的急性作用不同，但与临床结果有关。提出了一种“重置”治疗机制。
