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.