Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.
Robin L Carhart-Harris, Leor Roseman, Mark Bolstridge, Lysia Demetriou, J Nienke Pannekoek, Matthew B Wall, Mark Tanner, Mendel Kaelen, John Mcgonigle, Kevin Murphy, Robert Leech, H Valerie Curran, David J Nutt
Sci Rep October 13, 2017 DOI: 10.1038/s41598-017-13282-7 via PubMed Central
Summary
AI-generated from the abstractIn patients with treatment-resistant depression, a single dose of psilocybin combined with psychological support reduced depressive symptoms and altered brain activity and connectivity. Functional MRI scans before and after treatment showed decreased blood flow in the temporal cortex, including the amygdala, and increased resting-state functional connectivity within the default-mode network. Reduced amygdala blood flow correlated with fewer depressive symptoms. Changes in connectivity between the ventromedial prefrontal cortex and inferior lateral parietal cortex, as well as between the parahippocampus and prefrontal cortex, predicted treatment response at five weeks. These brain changes differ from the drug's acute effects and suggest a 'reset' of neural circuits.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 19 |
| Population | Patients with treatment-resistant depression |
| Intervention | Psilocybin |
| Duration | 1-week and 5-week follow-up |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Psychedelic Depression treatment Antidepressant Mental health therapy |
| Citations | 590 |
| Key finding | Psilocybin treatment decreased amygdala cerebral blood flow and increased default-mode network connectivity, with specific connectivity changes predicting clinical response at five weeks. |
Abstract
Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.