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.
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 |
| Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity. Patients with treatment-resistant depression or moderate-to-severe major depression | 2024 | Observational cohort | n = 38 |