Brain dynamics predictive of response to psilocybin for treatment-resistant depression

Vohryzek, J.; Cabral, J.; Lord, L.-D.; Fernandes, H. M.; Roseman, L.; Nutt, D. J.; Carhart-Harris, R. L.; Deco, G.; Kringelbach, M. L.

doi:10.1101/2022.06.30.497950

bioRxiv · 10.1101/2022.06.30.497950

Brain dynamics predictive of response to psilocybin for treatment-resistant depression

Vohryzek, J.·Cabral, J.·Lord, L.-D.·Fernandes, H. M.·Roseman, L.·Nutt, D. J.·Carhart-Harris, R. L.·Deco, G.·Kringelbach, M. L.

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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.

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Vohryzek, J., Cabral, J., Lord, L.-D., Fernandes, H. M., Roseman, L., Nutt, D. J., Carhart-Harris, R. L., Deco, G., Kringelbach, M. L.. 2022-07-04. Brain dynamics predictive of response to psilocybin for treatment-resistant depression. https://doi.org/10.1101/2022.06.30.497950

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