Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity.

Brain connectivity patterns measured before psilocybin treatment can predict how much depression symptoms will improve. In people with treatment-resistant depression given two doses of psilocybin (25 mg each, one week apart), baseline resting-state functional MRI scans showed that connectivity within visual, default mode, and executive networks predicted early symptom improvement, while salience network connectivity predicted who would respond up to 24 weeks later, with about 90% accuracy. Similar patterns appeared in a separate trial comparing psilocybin to escitalopram. Fronto-occipital and fronto-temporal connections predicted early and late symptom reduction, respectively. Small sample sizes and differences between datasets limit generalizability, and the lack of a placebo arm limits specificity.

Study at a glance

Abstract

BackgroundPsilocybin is a serotonergic psychedelic drug under assessment as a potential therapy for treatment-resistant and major depression. Heterogeneous treatment responses raise interest in predicting the outcome from baseline data.MethodsA machine learning pipeline was implemented to investigate baseline resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI) as a predictor of symptom severity in psilocybin monotherapy for treatment-resistant depression (16 patients administered two 5 mg capsules followed by 25 mg, separated by one week). Generalizability was tested in a sample of 22 patients who participated in a psilocybin vs. escitalopram trial for moderate-to-severe major depression (two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo vs. two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram). The analysis was repeated using both samples combined.ResultsFunctional connectivity of visual, default mode and executive networks predicted early symptom improvement, while the salience network predicted responders up to 24 weeks after treatment (accuracy≈0.9). Generalization performance was borderline significant. Consistent results were obtained from the combined sample analysis. Fronto-occipital and fronto-temporal coupling predicted early and late symptom reduction, respectively.LimitationsThe number of participants and differences between the two datasets limit the generalizability of the findings, while the lack of a placebo arm limits their specificity.ConclusionsBaseline neurophysiological measurements can predict the outcome of psilocybin treatment for depression. Future research based on larger datasets should strive to assess the generalizability of these predictions.