Katrin Preller, PhD
University of Zurich
Psilocybin induces time-dependent changes in global brain connectivity
Background: The use of Psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.
Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over study during which 23 healthy human participants received placebo and 0.2 mg/kg of psilocybin p.o. on two different test days. Participants underwent MRI scanning at three time points between administration and peak effects: 20 mins, 40 mins, and 70 mins after administration. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps.
Results: Psilocybin reduced associative, but concurrently increased sensory brain-wide connectivity. This pattern emerged over time from administration to peak-effects. Furthermore, we show that baseline connectivity is associated with the extent of Psilocybin-induced changes in functional connectivity. Lastly, Psilocybin-induced changes correlated time-dependently with spatial gene expression patterns of the 5-HTR2A and 5-HTR1A.
Conclusion: Together, these results suggest that the integration of sensory and the dis-integration of associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.
Katrin Preller, received her M.Sc. (Neuropsychology and Clinical Psychology) from University of Konstanz, Germany. For her PhD, Dr. Preller joined the Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Switzerland, where she investigated the neurobiological and social-cognitive long-term effects of cocaine, MDMA, and heroin use. After completing her PhD, she joined the Neuropsychopharmacology and Brain Imaging lab at the Psychiatric University Hospital Zurich, investigating the effects of psychedelic substances on self-perception, social cognition, and multimodal processing using different brain imaging techniques. Dr. Preller received a SNSF PostDoc mobility fellowship and worked as a Postdoc at the Wellcome Trust Centre for Neuroimaging, UCL, London, UK, and Yale University, New Haven, CT, USA. Subsequently, she was appointed as Junior Group Leader at the Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, and holds a position as Visiting Assistant Professor at Yale University School of Medicine. Dr. Preller is a recipient of the Pfizer Research Award and the Swiss Society for Biological Psychiatry Young investigators award. Her group’s research focus is centered on the neurobiology and pharmacology of cognitive and emotional processes in heath and disease using multi-modal behavioral, electrophysiological and neuroimaging techniques, the development of novel treatment approaches, and the interaction between pharmacological and non-pharmacological treatments.