Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
This open-label fMRI study (n=20) investigated amygdala responses to emotional stimuli in patients with treatment-resistant depression following psilocybin therapy. Unlike SSRIs which typically blunt amygdala responses, psilocybin increased responsiveness to fearful and happy faces, suggesting a therapeutic mechanism involving the reconnection with, rather than suppression of, emotions.
Authors
- Robin Carhart-Harris
- David Nutt
- Leor Roseman
Published
Abstract
Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post-psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.:
Research Summary of 'Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression'
Introduction
Roseman and colleagues situate their work in the recent renaissance of clinical research on classic psychedelics, noting growing evidence that psilocybin combined with psychological support can produce rapid reductions in depressive and anxiety symptoms. They outline a neurobiological rationale focused on the amygdala, a subcortical structure sensitive to emotionally salient stimuli that has been implicated in depression. Previous functional MRI studies in untreated depressed patients have often reported amygdala hyper-reactivity to negative stimuli, and conventional antidepressants such as SSRIs tend to attenuate amygdala responses early in treatment. The study aimed to test whether amygdala responses to emotional faces are altered after psilocybin treatment in people with treatment-resistant depression (TRD). Using a validated emotional faces fMRI paradigm, the investigators predicted that post-treatment amygdala reactivity would change relative to baseline and that such changes would relate to clinical measures of depressive symptoms. They paid particular attention to the fearful versus neutral contrast because prior SSRI work has emphasised attenuation to negative stimuli, and they also anticipated that aspects of the acute psychedelic experience might relate to subsequent changes in amygdala function.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J., & Carhart-Harris, R. L. (2018). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology, 142, 263-269. https://doi.org/10.1016/j.neuropharm.2017.12.041
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