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
September 20, 2022 DOI: 10.21203/rs.3.rs-2060381/v1
Summary
New neuroscience reveals how psilocybin helps overcome depression. By modeling brain activity, specific regions crucial for recovery were pinpointed in participants experiencing over 50% reduction in depressive symptoms following 10mg and 25mg psilocybin doses. These regions strongly correlate with serotonin receptor distribution, where psilocin, the active compound, acts. This Serotonergic mechanism provides causal evidence for how psychedelics impact mental health, linking serotonin pathways and functional brain connectivity to recovery from clinical depression. This advances Psychology and Drug Studies, addressing key Mental Health Research Topics.
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.