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Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Carhart-Harris, Robin L, Roseman, Leor, Bolstridge, Mark, Demetriou, Lysia, Pannekoek, J Nienke, Wall, Matthew B, Tanner, Mark, Kaelen, Mendel, McGonigle, John, Murphy, Kevin, Leech, Robert, Curran, H Valerie and Nutt, David J 2017. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports 7 (1) , 13187. 10.1038/s41598-017-13282-7

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Physics and Astronomy
Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 24 October 2017
Date of Acceptance: 19 September 2017
Last Modified: 30 Jun 2019 15:04
URI: http://orca.cf.ac.uk/id/eprint/105845

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