Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity.
Debora Copa, David Erritzøe, Bruna Giribaldi, David Nutt, Robin Carhart-Harris, Enzo Tagliazucchi
J Affect Disord February 27, 2024 DOI: 10.1016/j.jad.2024.02.089 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 38 |
| Population | Patients with treatment-resistant depression or moderate-to-severe major depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | 24-week follow-up |
| Topics | Psychedelic-assisted therapy Depression Psilocybin |
| Keywords | Psilocybin therapy Psilocybin treatment Psychedelics for depression Brain imaging FMRI Neuroimaging Brain scans Functional connectivity Neural signatures Brain activity Personalized medicine Precision medicine Tailored therapy Predictive biomarkers Individualized treatment Depression treatment Mental health treatment Antidepressant therapy |
| Citations | 31 |
| Key findings | Baseline resting-state functional connectivity of visual, default mode, executive, and salience networks predicted symptom improvement up to 24 weeks after psilocybin treatment, with accuracy around 0.9. |
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.
Comparable studies
Other observational and cohort studies on psilocybin and psychedelic-assisted therapy, most cited first.