On the relationship of first-episode psychosis to the amphetamine-sensitized state
- Author(s)
- Ana Weidenauer, Martin Bauer, Ulrich Sauerzopf, Lucie Bartova, Lukas Nics, Sarah Pfaff, Cecile Philippe, Neydher Berroterán-Infante, Verena Pichler, Bernhard M Meyer, Ulrich Rabl, Patrick Sezen, Paul Cumming, Thomas Stimpfl, Harald H Sitte, Rupert Lanzenberger, Nilufar Mossaheb, Alexander Zimprich, Pablo Rusjan, Georg Dorffner, Markus Mitterhauser, Marcus Hacker, Lukas Pezawas, Siegfried Kasper, Wolfgang Wadsak, Nicole Praschak-Rieder, Matthäus Willeit
- Abstract
Schizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of "endogenous" sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and positron emission tomography. Healthy volunteers (n = 28, 14 female) underwent a baseline and then a post-amphetamine scan before and after a mildly sensitizing regimen of repeated oral amphetamine. Unmedicated patients with first-episode psychosis (n = 21; 6 female) underwent a single pair of baseline and then post-amphetamine scans. Furthermore, T1 weighted magnetic resonance imaging of the prefrontal cortex was performed. Patients with first-episode psychosis showed larger release of dopamine compared to healthy volunteers. After sensitization of healthy volunteers their dopamine release was significantly amplified and no longer different from that seen in patients. Healthy volunteers showed a negative correlation between prefrontal cortical volume and dopamine release. There was no such relationship after sensitization or in patients. Our data in patients with untreated first-episode psychosis confirm the "endogenous sensitization" hypothesis and support the notion of impaired prefrontal control of the dopamine system in schizophrenia.
- Organisation(s)
- External organisation(s)
- Medizinische Universität Wien, University of Toronto, Ludwig Boltzmann Intitute Applied Diagnostics, Queensland University of Technology, Universitätsspital Bern (Inselspital)
- Journal
- Translational Psychiatry
- Volume
- 10
- No. of pages
- 11
- ISSN
- 2158-3188
- DOI
- https://doi.org/10.1038/s41398-019-0681-5
- Publication date
- 01-2020
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 302054 Nuclear medicine
- Keywords
- ASJC Scopus subject areas
- Psychiatry and Mental health, Biological Psychiatry, Cellular and Molecular Neuroscience
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/d3e44412-37b0-4f25-8bc5-524bd03540ad