Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder.
Level 4 - case-series / case-control
Open-label, single-arm before-and-after study without a control group.
PubMed 34750350 · doi:10.1038/s41398-021-01706-y
What was done
In an open-label study, 24 patients with major depressive disorder received psilocybin therapy. Researchers evaluated cognitive flexibility (perseverative errors on a set-shifting task) for at least 4 weeks post-treatment. At 1 week post-treatment, they measured neurometabolite concentrations (glutamate and N-acetylaspartate) via magnetic resonance spectroscopy and neural flexibility (dynamic functional connectivity, or dFC) via functional magnetic resonance imaging, focusing on regions such as the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC).
What was found
The abstract reports directional changes without providing exact numerical values, effect sizes, or p-values. Cognitive flexibility increased for at least 4 weeks following treatment, but these improvements did not correlate with previously reported antidepressant responses. At 1 week post-treatment, glutamate and N-acetylaspartate concentrations in the ACC decreased, while dFC between the ACC and PCC increased. Greater increases in ACC-PCC connectivity were associated with smaller improvements in cognitive flexibility. Connectome-based predictive modeling showed that higher baseline ACC dynamic functional connectivity correlated with better baseline cognitive flexibility but predicted less post-treatment cognitive improvement.
Why it matters
This study provides preliminary human neuroimaging and metabolite evidence linking psilocybin therapy to enduring shifts in frontocingulate neural dynamics and set-shifting performance, demonstrating that cognitive improvements can occur independently of mood changes.
Limits
The study is limited by a small sample size (n = 24), an open-label design lacking a placebo or active control group, and the absence of specific numerical statistics or confidence intervals in the abstract. Long-term follow-up beyond 4 weeks was not reported.