Single-dose psilocybin alters resting state functional networks in patients with body dysmorphic disorder

Body dysmorphic disorder (BDD) is a severe psychiatric condition characterized by preoccupation with perceived flaws in one's appearance, which the individual views as defective or ugly. Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, has emerged as a potential therapeutic agent for depression and other psychiatric disorders. This study aimed to identify subacute neural changes predicting symptomatic response to psilocybin treatment in adults with BDD. Eight adults with moderate-to-severe nondelusional BDD were administered a single oral 25 mg dose of psilocybin, accompanied by psychological support, and underwent resting state functional magnetic resonance imaging assessments 1 day before and 1 day after the dosing. Both a region of interest (ROI)-to-ROI analysis and multivariate pattern analysis (MVPA) were used to identify changes in resting state functional connectivity (rsFC) at day 1 after dosing that predicted treatment response at week 1, measured by change in Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDDYBOCS) score. All participants completed the dosing and follow-up assessments over 12 weeks. BDD-YBOCS scores decreased at week 1 and week 12 after dosing (p<0.001 for both). MVPA revealed a significant increase in rsFC within the Executive Control Network (ECN) at day 1. Increased rsFC within the ECN (dlPFC - Superior Parietal Lobule [FPL]), between the ECN and Default Mode Network (dlPFC - Precuneus), and between the ECN and the Salience Network (dlPFC - insula) were predictive of improvement in BDD symptoms at week 1. These findings are the first report of subacute brain effects of psilocybin in patients with BDD. Given the small sample size and uncontrolled design of the study, larger controlled studies are necessary to validate these observations. Clinical Trials Registration: Clinicaltrials.gov ID: NCT04656301.