Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed action of antidepressants, we recently found increased right amygdala responsiveness to fearful faces one day after treatment with psilocybin in 19 patients with treatment-resistant depression (TRD), which correlated with treatment efficacy. This was interpreted as regained emotional responsiveness post-treatment.
AIMS: The present study constitutes an extension to this basic activation analysis. We hypothesized changes in amygdala functional connectivity during emotional face processing after treatment with psilocybin. More precisely, we predicted that decreased functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) may underlie the previously observed increase in amygdala responsivity.
METHODS: Psychophysiological interaction analyses were conducted on functional Magnetic Resonance Imaging (fMRI) data from a classic face/emotion perception task, with the bilateral amygdala and vmPFC time-series as physiological regressors.
RESULTS: Results showed decreased vmPFC-right amygdala functional connectivity during face processing post- (versus pre-) treatment, and this was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and vmPFC to occipital-parietal cortices during face processing.
CONCLUSION: These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level – which may be a key treatment mechanism for psychedelic therapy. Future placebo-controlled studies are needed to examine the replicability of the current findings.