Serotonergic neurotransmission in emotional processing: New evidence from long-term recreational poly-drug ecstasy use.
The brain's serotonergic system plays a crucial role in the processing of emotional stimuli, and several studies have shown that a reduced serotonergic neurotransmission is associated with an increase in amygdala activity during emotional face processing. Prolonged recreational use of ecstasy (3,4-methylene-dioxymethamphetamine [MDMA]) induces alterations in serotonergic neurotransmission that are comparable to those observed in a depleted state. In this functional magnetic resonance imaging (fMRI) study, we investigated the responsiveness of the amygdala to emotional face stimuli in recreational ecstasy users as a model of long-term serotonin depletion. Fourteen ecstasy users and 12 non-using controls underwent fMRI to measure the regional neural activity elicited in the amygdala by male or female faces expressing anger, disgust, fear, sadness, or no emotion. During fMRI, participants made a sex judgement on each face stimulus. Positron emission tomography with11C-DASB was additionally performed to assess serotonin transporter (SERT) binding in the brain. In the ecstasy users, SERT binding correlated negatively with amygdala activity, and accumulated lifetime intake of ecstasy tablets was associated with an increase in amygdala activity during angry face processing. Conversely, time since the last ecstasy intake was associated with a trend toward a decrease in amygdala activity during angry and sad face processing. These results indicate that the effects of long-term serotonin depletion resulting from ecstasy use are dose-dependent, affecting the functional neural basis of emotional face processing.
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Helle Ruff
HR
Laursen
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
Susanne
S
Henningsson
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.|Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Julian
J
Macoveanu
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Terry L
TL
Jernigan
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.|Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
Hartwig R
HR
Siebner
Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.|Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
Klaus K
KK
Holst
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Arnold
A
Skimminge
Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.|Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Gitte M
GM
Knudsen
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Center for Decision Neuroscience, Copenhagen Business School, Copenhagen, Denmark.|Singularity University, Moffett Field, CA, USA.|Neurons, Inc., Holbæk, Denmark.
Thomas Z
TZ
Ramsoy
Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark d.erritzoe@imperial.ac.uk daviderritzoe@gmail.com.|Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Centre for Neuropsychopharmacology, Imperial College London, London, UK.
David
D
Erritzoe
D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004644:Emotions / Q000187:drug effects*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D049268:Positron-Emission Tomography / Q000379:methods; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D055815:Young Adult
D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine
MDMA; amygdala; ecstasy; emotion; fMRI; serotonin