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
Brain Communications 2024 DOI: 10.1093/braincomms/fcae049 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Responders and non-responders to psilocybin therapy for depression |
| Intervention | Psilocybin |
| Dose | 10 and 25 mg |
| Duration | 7 days apart |
| Topics | Depression Psilocybin |
| Keywords | Large-scale brain modelling Psilocybin treatment Psilocybin therapy Neuroscience research Depression treatment Brain mapping Predictive medicine |
| Citations | 33 |
| Key findings | Brain regions identified through dynamic sensitivity analysis of large-scale models correlate with serotonin receptor densities and are implicated in transitioning from a depressive to a healthy brain state via psilocybin. |
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 (10 and 25 mg, 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 healthy 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.