Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression

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• dc.contributor.author Deco, Gustavo
• dc.contributor.author Sanz Perl, Yonatan
• dc.contributor.author Johnson, Samuel
• dc.contributor.author Bourke, Niamh
• dc.contributor.author Carhart-Harris, Robin L.
• dc.contributor.author Kringelbach, Morten L.
• dc.contributor.other Trastorns neuroconductuals
• dc.date.accessioned 2025-06-17T09:09:32Z
• dc.date.available 2025-06-17T09:09:32Z
• dc.date.issued 2024
• dc.description.abstract Effective interventions for neuropsychiatric disorders may work by rebalancing the brain’s functional hierarchical organization. Here we directly investigated the effects of two different serotonergic pharmacological interventions on functional brain hierarchy in major depressive disorder in a two-arm double-blind phase II randomized controlled trial comparing psilocybin therapy (22 patients) with escitalopram (20 patients). Patients with major depressive disorder received either 2 × 25 mg of oral psilocybin, three weeks apart, plus six weeks of daily placebo (‘psilocybin arm’) or 2 × 1 mg of oral psilocybin, three weeks apart, plus six weeks of daily escitalopram (10–20 mg; ‘escitalopram arm’). Resting-state functional magnetic resonance imaging scans were acquired at baseline and three weeks after the second psilocybin dose (NCT03429075). The brain mechanisms were captured by generative effective connectivity, estimated from whole-brain modeling of resting state for each session and patient. Hierarchy was determined for each of these sessions using measures of directedness and trophic levels on the effective connectivity, which captures cycle structure, stability and percolation. The results showed that the two pharmacological interventions created significantly different hierarchical reconfigurations of whole-brain dynamics with differential, opposite statistical effect responses. Furthermore, the use of machine learning revealed significant differential reorganization of brain hierarchy before and after the two treatments. Machine learning was also able to predict treatment response with an accuracy of 0.85 ± 0.04. Overall, the results demonstrate that psilocybin and escitalopram work in different ways for rebalancing brain dynamics in depression. This suggests the hypothesis that neuropsychiatric disorders could be closely linked to the breakdown in regions orchestrating brain dynamics from the top of the hierarchy.
• dc.description.sponsorship G.D. is supported by grant no. PID2022-136216NB-I00 funded by MICIU/AEI/10.13039/501100011033 and by ‘ERDF A way of making Europe’, ERDF, EU, Project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS; ref. 101071900) funded by the EU ERC Synergy Horizon Europe, and AGAUR research support grant (ref. 2021 SGR 00917) funded by the Department of Research and Universities of the Generalitat of Catalunya. Y.S.P. is supported by the project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS; ref. 101071900) funded by the EU ERC Synergy Horizon Europe. M.L.K. is supported by the Centre for Eudaimonia and Human Flourishing (funded by the Pettit and Carlsberg Foundations) and the Center for Music in the Brain (funded by the Danish National Research Foundation, DNRF117). The neuroimaging analysis and whole-brain modeling is based on clinical research carried out at the National Institute for Health Research/Wellcome Trust Imperial Clinical Research Facility. The open-label trial was funded by a Medical Research Council clinical development scheme grant (MR/J00460X/1). The double-blind randomized controlled trial was funded by a private donation from the Alexander Mosley Charitable Trust, supplemented by Founders of Imperial College London’s Centre for Psychedelic Research. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper.
• dc.format.mimetype application/pdf
• dc.identifier.citation Deco G, Sanz Perl Y, Johnson S, Bourke N, Carhart-Harris RL, Kringelbach ML. Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression. Nat Ment Health. 2024;2:1096-110. DOI: 10.1038/s44220-024-00298-y
• dc.identifier.doi http://dx.doi.org/10.1038/s44220-024-00298-y
• dc.identifier.issn 2731-6076
• dc.identifier.uri http://hdl.handle.net/10230/70700
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Mental Health. 2024;2:1096-110
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101071900
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136216NB-I00
• dc.rights © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Depressió psíquica
• dc.subject.other Neurofarmacologia
• dc.title Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion