Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in mahor depressive disorder

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• dc.contributor.author Escrichs, Anira
• dc.contributor.author Sanz Perl, Yonatan
• dc.contributor.author Fisher, Patrick M.
• dc.contributor.author Martínez-Molina, Noelia
• dc.contributor.author G-Guzman, Elvira
• dc.contributor.author Frokjaer, Vibe G.
• dc.contributor.author Kringelbach, Morten L.
• dc.contributor.author Knudsen, Gitte M.
• dc.contributor.author Deco, Gustavo
• dc.date.accessioned 2025-03-27T08:16:32Z
• dc.date.available 2025-03-27T08:16:32Z
• dc.date.issued 2025
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract Depression is a multifactorial clinical syndrome with a low pharmacological treatment response rate. Therefore, identifying predictors of treatment response capable of providing the basis for future developments of individualized therapies is crucial. Here, we applied model-free and model-based measures of whole-brain turbulent dynamics in resting-state functional magnetic resonance imaging (fMRI) in healthy controls and unmedicated depressed patients. After eight weeks of treatment with selective serotonin reuptake inhibitors (SSRIs), patients were classified as responders and non-responders according to the Hamilton Depression Rating Scale 6 (HAMD6). Using the model-free approach, we found that compared to healthy controls and responder patients, non-responder patients presented disruption of the information transmission across spacetime scales. Furthermore, our results revealed that baseline turbulence level is positively correlated with beneficial pharmacological treatment outcomes. Importantly, our model-free approach enabled prediction of which patients would turn out to be non-responders. Finally, our model-based approach provides mechanistic evidence that non-responder patients are less sensitive to stimulation and, consequently, less prone to respond to treatment. Overall, we demonstrated that different levels of turbulent dynamics are suitable for predicting response to SSRIs treatment in depression.
• dc.description.sponsorship AE was supported by the project eBRAIN-Health—Actionable Multilevel Health Data (id 101058516), funded by EU Horizon Europe and by the Grant PID2022-136216NB-I00, funded by MICIU/AEI/10.13039/501100011033, and “ERDF A way of making Europe”, ERDF, EU. YSP was supported by the project NEurological MEchanismS of Injury, and the project Sleep-like cellular dynamics (NEMESIS) (ref. 101071900) funded by the EU ERC Synergy Horizon Europe. GD was supported by the project NEurological MEchanismS of Injury, and the project Sleep-like cellular dynamics (NEMESIS) (ref. 101071900) funded by the EU ERC Synergy Horizon Europe and and by the Grant PID2022-136216NB-I00, funded by MICIU/AEI/10.13039/501100011033, and “ERDF A way of making Europe”, ERDF, EU. MLK is supported by the Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117), and Center for Eudaimonia and Human Flourishing at Linacre College funded by the Pettit and Carlsberg Foundations. Data were acquired through the NeuroPharm project (www.neuropharm.eu), funded by grant 4108-00004B from the Innovation Fund Denmark, grant R279-2018-1145 from The Lundbeck Foundation Alliance BrainDrugs, the Research Fund of the Mental Health Services–Capital Region of Denmark, grant R149-A6325 from the Research Council of Rigshospitalet, grant 16-0058 from the AugustinusFoundation, grants from Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, and grantsDFF-6120-00038 and DFF-1057-00052B from the Independent Research Fund Denmark.
• dc.format.mimetype application/pdf
• dc.identifier.citation Escrichs A, Sanz Perl Y, Fisher PM, Martínez-Molina N, G-Guzman E, Frokjaer VG, et al. Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in mahor depressive disorder. Mol Psychiatry. 2025;30:1069-79. DOI: 10.1038/s41380-024-02690-7
• dc.identifier.doi http://dx.doi.org/10.1038/s41380-024-02690-7
• dc.identifier.issn 1069-1079
• dc.identifier.uri http://hdl.handle.net/10230/70031
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Molecular Psychiatry. 2025;30:1069-79
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101058516
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101071900
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136216NB-I00
• dc.rights 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 -- Tractament
• dc.title Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in mahor depressive disorder
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion