Brain dynamics predictive of response to psilocybin for treatment-resistant depression.
Jakub Vohryzek, Joana Cabral, Louis-David Lord, Henrique M Fernandes, Leor Roseman, David J Nutt, Robin L Carhart-Harris, Gustavo Deco, Morten L Kringelbach
Brain communications January 1, 2024 DOI: 10.1093/braincomms/fcae049 via PubMed
Summary
AI-generated from the abstractPsilocybin therapy for depression shows promise, but its causal mechanisms are unknown. By comparing brain dynamics in treatment responders (those with >50% symptom reduction) and non-responders before treatment, researchers used large-scale brain modeling to identify brain regions whose perturbation could shift a depressive brain state to a healthy one. The identified regions correlated with density maps of serotonin receptors 5-HT2a and 5-HT1a, where psilocin (psilocybin's active metabolite) acts as an agonist. These findings provide causal mechanistic evidence linking specific brain regions and serotonergic transmission to recovery from depression via psilocybin.
Study at a glance
| 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 |
| Keywords | Large-scale brain modelling Psilocybin treatment Psilocybin therapy Neuroscience research Depression treatment |
| Citations | 33 |
| Key finding | 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.