Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises
Molecular Psychiatry – April 26, 2025
Source: OpenAlex
Summary
Psilocybin therapy significantly reduces anhedonia in Major Depressive Disorder, a key insight for **Psychology** and **Psychiatry**. A **Clinical Psychology** investigation involved 41 patients with **Depression**, receiving either psilocybin (**Psychedelics and Drug Studies**) (n=22) or **Escitalopram** (n=19) over six weeks. Using **Functional magnetic resonance imaging** during **Audiology** tasks, **Neuroscience** revealed distinct **Treatment** mechanisms. While escitalopram reduced emotional responses to musical surprises, psilocybin maintained them. This suggests psilocybin influences **Cognitive Processes** differently, via **Neurotransmitter Receptor Influence on Behavior**, offering varied **Psychometrics** outcomes for **Anxiety** and depression.
Abstract
Abstract Psilocybin therapy (PT) is emerging as an effective intervention for Major Depressive Disorder (MDD), offering comparable efficacy to conventional treatments like selective serotonin reuptake inhibitors (SSRIs). Music, an emotionally evocative stimulus, provides a valuable tool to explore changes in hedonic and predictive processing mechanisms via expectancy violations, or ‘surprises’. This study sought to compare behavioural and functional magnetic resonance imaging (fMRI) responses to musical surprises in MDD patients treated with either PT or the SSRI, escitalopram. In this secondary analysis of a trial, 41 MDD patients (with usable fMRI data) were randomly assigned to either PT ( n = 22) or escitalopram ( n = 19) treatment groups. Participants listened to music during fMRI and tracked their emotional experience, both before and after a 6-week intervention. Surprise-related valence and arousal indices were calculated. Musical surprises were entered as regressors for whole-brain and region of interest fMRI analyses. PT caused a greater decrease in anhedonia scores compared with escitalopram. While escitalopram led to reductions in surprise-related affective responses, PT showed no significant change. Escitalopram was associated with increased activation in memory and emotional processing areas during musical surprises (versus control events) when compared with PT. Following PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. PT may allow for the subjective response to musical surprises to be maintained through a lasting reduction in the salience of prediction errors, or, alternatively, by increasing hedonic priors. Contrastingly, escitalopram may diminish hedonic priors, highlighting fundamental differences in treatment mechanisms.