On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study.

Weidenauer, Ana; Bauer, Martin; Sauerzopf, Ulrich; Bartova, Lucie; Nics, Lukas; Pfaff, Sarah; Philippe, Cecile; Berroterán-Infante, Neydher; Pichler, Verena; Meyer, Bernhard M; Rabl, Ulrich; Sezen, Patrick; Cumming, Paul; Stimpfl, Thomas; Sitte, Harald H; Lanzenberger, Rupert; Mossaheb, Nilufar; Zimprich, Alexander; Rusjan, Pablo; Dorffner, Georg; ... (2020). On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study. Translational Psychiatry, 10(1), p. 2. Springer Nature 10.1038/s41398-019-0681-5

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Cumming, Paul

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2158-3188

Publisher:

Springer Nature

Language:

English

Submitter:

Sabine Lanz

Date Deposited:

04 Jan 2021 08:33

Last Modified:

10 Mar 2021 20:20

Publisher DOI:

10.1038/s41398-019-0681-5

PubMed ID:

32066718

BORIS DOI:

10.48350/149397

URI:

https://boris.unibe.ch/id/eprint/149397

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