Brain dynamics predictive of response to psilocybin for treatment-resistant depression
Jakub Vohryzek, Joana Cabral, Louis-David Lord, Henrique M. Fernandes, Leor Roseman, David Nutt, Robin Carhart-Harris, Gustavo Deco, Morten L. Kringelbach
Research Square September 20, 2022 preprint DOI: 10.21203/rs.3.rs-2060381/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Population | Patients with depression receiving psilocybin therapy |
| Intervention | Psilocybin |
| Dose | 10mg and 25mg, 7 days apart |
| Topics | Psilocybin Serotonin Depression |
| Keywords | Anhedonia Depression economics Hallucinogen Receptor |
| Citations | 10 |
| Key findings | Brain regions implicated in recovery from depression after psilocybin therapy correlate with serotonin 5-HT2A and 5-HT1A receptor density, providing causal mechanistic evidence for the role of serotonergic transmission. |
Abstract
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 whole-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-HT2A and 5-HT1A, 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.
Comparable studies
Other observational and cohort studies on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression | 2017 | Observational cohort | n = 19 |
| Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression Patients with treatment-resistant depression and healthy controls | 2017 | Observational cohort | n = 33 |
| More Realistic Forecasting of Future Life Events After Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression (TRD) | 2018 | Observational cohort | n = 15 |
| Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. 17 patients with treatment-resistant depression and 18 untreated age-matched healthy... | 2018 | Observational cohort with machine learning classification | n = 35 |
| Brain dynamics predictive of response to psilocybin for treatment-resistant depression. Responders and non-responders to psilocybin therapy for depression | 2024 | Observational cohort |
Citations in the library
Cited by 4
- Psychedelia: The interplay of music and psychedelics Annals of the New York Academy of Sciences November 20, 2023
- Harmonic decomposition of spacetime (HADES) framework characterises the spacetime hierarchy of the DMT brain state bioRxiv August 21, 2023
- Inducing a meditative state by artificial perturbations: A causal mechanistic understanding of brain dynamics underlying meditation bioRxiv Preprint Server July 27, 2023
- Dynamic Repertoire of Brain Networks in Mindfulness-Based Cognitive Therapy During Rumination: A Randomized Controlled Trial Biological Psychiatry Global Open Science May 14, 2026
Cites 15
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Ongoing Cortical Activity at Rest: Criticality, Multistability, and Ghost Attractors Journal of Neuroscience March 7, 2012
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Increased global integration in the brain after psilocybin therapy for depression. Nature Medicine April 11, 2022
and 10 more in the library