title: The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity.
abstract: Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual-limbic-prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zürich 8032, Switzerland; Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zürich 8032, Switzerland. Electronic address: r.kraehenmann@bli.uzh.ch.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kraehenmann
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Basel 4012, Switzerland; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 AF, United Kingdom.
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Wellcome Centre for Imaging Neuroscience, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Karl
authors.initials: K
authors.lastname: Friston
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zürich 8032, Switzerland.
authors.forename: Katrin H
authors.initials: KH
authors.lastname: Preller
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zürich 8032, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zürich 8032, Switzerland.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D001499:Bayes Theorem; D001931:Brain Mapping; D005239:Fear / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects; D011562:Psilocybin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D017366:Serotonin Receptor Agonists; D011562:Psilocybin
keywords: Depression; Dynamic causal modeling; Psilocybin; Serotonin; fMRI