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Negative affective bias in depression following treatment with psilocybin or escitalopram – a secondary analysis from a randomized trial

Summary

This research compared how psilocybin mushrooms and escitalopram (a common antidepressant) affect the way depressed people perceive emotions. Both treatments helped patients become better at recognizing positive facial expressions and less likely to misinterpret neutral or positive faces as negative. Interestingly, while both treatments improved emotional processing similarly, the improvements were connected to later mood improvement in different ways for each drug, suggesting they may work through somewhat different mechanisms in the brain.

Background

Current antidepressant treatments like SSRIs have limited efficacy and slow onset of action. Psilocybin has emerged as a potential novel antidepressant treatment, but it remains unclear what neuropsychological mechanisms underpin its therapeutic effects compared to conventional antidepressants.

Objective

To investigate whether psilocybin and escitalopram produce shared or distinct effects on emotional information processing, specifically examining changes in negative affective bias using a validated facial emotion recognition task.

Results

Both psilocybin and escitalopram produced comparable reductions in negative affective bias at 6 weeks, with decreased accuracy for recognizing negative faces and fewer misclassifications. Longitudinally, decreased negative bias was associated with subsequent depression improvement for escitalopram but not psilocybin, suggesting differential mechanisms of therapeutic action.

Conclusion

Both psilocybin and escitalopram demonstrated a shift toward more positive emotional processing bias, though the temporal relationship with clinical improvement differed between treatments, suggesting overlapping but potentially distinct neuropsychological mechanisms.
  • Published in:Translational Psychiatry,
  • Study Type:Randomized Controlled Trial,
  • Source: PMID: 41257994, DOI: 10.1038/s41398-025-03693-w
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