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
Author Information
Jakub Vohryzek: Department of Psychiatry, University of Oxford, Oxford, UK.
Joana Cabral: Department of Psychiatry, University of Oxford, Oxford, UK.
Louis-David Lord: Department of Psychiatry, University of Oxford, Oxford, UK.
Henrique M Fernandes: Department of Psychiatry, University of Oxford, Oxford, UK.
Leor Roseman: Centre for Psychedelic Research, Department of Brain Sciences, Imperial College London, London, UK.
David J Nutt: Centre for Psychedelic Research, Department of Brain Sciences, Imperial College London, London, UK.
Robin L Carhart-Harris: Centre for Psychedelic Research, Department of Brain Sciences, Imperial College London, London, UK.
Gustavo Deco: Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.
Morten L Kringelbach: Department of Psychiatry, University of Oxford, Oxford, UK.
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 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.
