Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA
Ottavia Dipasquale, Pierluigi Selvaggi, Mattia Veronese, Anthony S. Gabay, Federico Turkheimer, Mitul A. Mehta
Neuroimage April 4, 2019 DOI: 10.1016/j.neuroimage.2019.04.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, crossover study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy subjects |
| Interventions | 3 4-methylenedioxymethamphetamine (MDMA) |
| Topics | MDMA Serotonin |
| Keywords | Serotonin transporter Pharmacology Connectome Receptor |
| Citations | 79 |
| Key points | MDMA-induced changes in functional connectivity are specifically linked to brain regions enriched with the serotonin transporter (5-HTT) and 5-HT1A receptor, with 5-HT1A changes correlating with drug levels and 5-HT2A changes correlating with spiritual experiences. |
Abstract
One of the main limitations of pharmacological fMRI is its inability to provide a molecular insight into the main effect of compounds, leaving an open question about the relationship between drug effects and haemodynamic response. The aim of this study is to investigate the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on functional connectivity (FC) using a novel multimodal method (Receptor-Enriched Analysis of functional Connectivity by Targets - REACT). This approach enriches the resting state (rs-)fMRI analysis with the molecular information about the distribution density of serotonin receptors in the brain, given the serotonergic action of MDMA. Twenty healthy subjects participated in this double-blind, placebo-controlled, crossover study. A high-resolution in vivo atlas of four serotonin receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) and its transporter (5-HTT) was used as a template in a two-step multivariate regression analysis to estimate the spatial maps reflecting the whole-brain connectivity behaviour related to each target under placebo and MDMA. Results showed that the networks exhibiting significant changes after MDMA administration are the ones informed by the 5-HTT and 5-HT1A distribution density maps, which are the main targets of this compound. Changes in the 5-HT1A-enriched functional maps were also associated with the pharmacokinetic levels of MDMA and MDMA-induced FC changes in the 5-HT2A-enriched maps correlated with the spiritual experience subscale of the Altered States of Consciousness Questionnaire. By enriching the rs-fMRI analysis with molecular data of voxel-wise distribution of the serotonin receptors across the brain, we showed that MDMA effects on FC can be understood through the distribution of its main targets. This result supports the ability of this method to characterise the specificity of the functional response of the brain to MDMA binding to serotonergic receptors, paving the way to the definition of a new fingerprint in the characterization of new compounds and potentially to a further understanding to the response to treatment.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 18
- In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape Science Advances June 14, 2023
- Differential contributions of serotonergic and dopaminergic functional connectivity to the phenomenology of LSD Psychopharmacology March 24, 2022
- Toward Mapping Neurobehavioral Heterogeneity of Psychedelic Neurobiology in Humans Biological Psychiatry December 7, 2022
- Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder. Frontiers in Psychiatry 2022
- A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy Frontiers in Psychiatry October 12, 2022
and 13 more in the library
Cites 27
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and 22 more in the library