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  Brain dynamics predictive of response to psilocybin for treatment-resistant depression

Vohryzek, J., Cabral, J., Lord, L.-D., Fernandes, H. M., Roseman, L., Nutt, D. J., et al. (2024). Brain dynamics predictive of response to psilocybin for treatment-resistant depression. Brain Communications, 6(2): fcae049. doi:10.1093/braincomms/fcae049.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000E-7E7D-A Version Permalink: https://hdl.handle.net/21.11116/0000-000F-1469-5
Genre: Journal Article

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 Creators:
Vohryzek, Jakub1, 2, 3, Author
Cabral, Joana1, 2, 4, 5, Author
Lord, Louis-David1, 2, Author
Fernandes, Henrique M.1, 2, Author
Roseman, Leor6, Author
Nutt, David J.6, Author
Carhart-Harris, Robin L.6, 7, Author
Deco, Gustavo3, 8, 9, 10, Author           
Kringelbach, Morten L.1, 2, 4, Author
Affiliations:
1Department of Psychiatry, University of Oxford, United Kingdom, ou_persistent22              
2Center for Music in the Brain, Aarhus University, Denmark, ou_persistent22              
3Department of Information and Communication Technologies, Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
4ICVS - Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal, ou_persistent22              
5ICVS/3B’s - PT Government Associate Laboratory, Braga, Portugal, ou_persistent22              
6Psychedelic Research Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom, ou_persistent22              
7Neuroscape Psychedelics Division, University of California, San Francisco, CA, USA, ou_persistent22              
8Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
9Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634551              
10School of Psychological Sciences, Monash University, Melbourne, Australia, ou_persistent22              

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Free keywords: Large-scale brain modelling; Psilocybin treatment; Depression
 Abstract: Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-Hydroxytryptamine 2a and 5-Hydroxytryptamine 1a, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.

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Language(s): eng - English
 Dates: 2023-10-162023-03-062023-11-012024-02-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1093/braincomms/fcae049
Other: eCollection 2024
PMID: 38515439
PMC: PMC10957168
 Degree: -

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Project name : -
Grant ID : 101017716; 720270; 785907
Funding program : Horizon 2020
Funding organization : European Union
Project name : -
Grant ID : 615539
Funding program : -
Funding organization : European Research Council (ERC)
Project name : -
Grant ID : DNRF117
Funding program : -
Funding organization : Danish National Research Foundation (DNRF)
Project name : -
Grant ID : CEECIND/03325/2017; UIDB/50026/2020; UIDP/50026/2020
Funding program : -
Funding organization : Portuguese Foundation for Science and Technology
Project name : -
Grant ID : -
Funding program : Spanish Research Project PSI2016-75688-P
Funding organization : European Union
Project name : -
Grant ID : 2017 SGR 1545
Funding program : -
Funding organization : Catalan Agency for Management of University and Research

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Title: Brain Communications
Source Genre: Journal
 Creator(s):
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Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 6 (2) Sequence Number: fcae049 Start / End Page: - Identifier: ISSN: 2632-1297
CoNE: https://pure.mpg.de/cone/journals/resource/2632-1297