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Associations Between Escitalopram and Psilocybin Therapy and Brain Resting-State Functional Connectivity in Major Depressive Disorder

Summary

This study compared how two depression treatments—a common antidepressant called escitalopram and psilocybin therapy—affect brain connectivity and depression symptoms. Both treatments reduced feelings of lacking pleasure and impulsive behaviors in depressed patients. The research found that while both worked, they affected different parts of the brain’s reward system in distinct ways, suggesting they may work through different mechanisms.

Background

Major Depressive Disorder is characterized by anhedonia and impulsivity, both linked to alterations in reward system function involving the striatum. Selective serotonin reuptake inhibitors are first-line treatments, while recent evidence suggests psychedelics may modulate reward systems.

Objective

This study aimed to investigate the effects of escitalopram and psilocybin therapy on reward pathways in the striatal subdivisions, amygdala, and hippocampus in MDD patients using seed-voxel analysis of resting-state fMRI data.

Results

Both treatment groups showed reductions in impulsivity and anhedonia. Significant interaction effects were found in amygdala network connectivity and limbic striatal networks. Psilocybin showed increased connectivity between amygdala and temporoparietal regions, while escitalopram showed reduced connectivity between limbic striatum and insula, correlating with anhedonia reduction.

Conclusion

The results demonstrate varying treatment effects on striatal connectivity between escitalopram and psilocybin therapy, revealing implicit differences in how these treatments affect underlying neural circuitry implicated in depression symptoms.
  • Published in:International Journal of Neuropsychopharmacology,
  • Study Type:Clinical Trial - Secondary Analysis,
  • Source: 10.1093/ijnp/pyae059.237, PMC11814992
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