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  Striatal dopamine and reward prediction error signaling in unmedicated schizophrenia patients

Katthagen, T., Kaminski, J., Heinz, A., Buchert, R., & Schlagenhauf, F. (2020). Striatal dopamine and reward prediction error signaling in unmedicated schizophrenia patients. Schizophrenia Bulletin, 46(6), 1535-1546. doi:10.1093/schbul/sbaa055.

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 Creators:
Katthagen, Teresa1, Author
Kaminski, Jakob1, 2, 3, Author
Heinz, Andreas1, 2, 4, Author
Buchert, Ralph5, Author
Schlagenhauf, Florian1, 3, 6, Author              
Affiliations:
1Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany, ou_persistent22              
2Berlin Institute of Health (BIH), Germany, ou_persistent22              
3Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
4NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Germany, ou_persistent22              
5Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
6Bernstein Center for Computational Neuroscience, Berlin, Germany, ou_persistent22              

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Free keywords: PET; Computational psychiatry; fMRI; Psychosis; Reinforcement learning; Reversal learning
 Abstract: Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Kicer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Kicer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Kicer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Kicer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Kicer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.

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Language(s): eng - English
 Dates: 2020-04-222020-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1093/schbul/sbaa055
PMID: 32318717
PMC: PMC7751190
 Degree: -

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Project name : -
Grant ID : SCHL 1969/1-1/1-2/3-1/4-1
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft DFG
Project name : -
Grant ID : BU 1441/4-1/4-2
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft DFG
Project name : -
Grant ID : 01GQ0411, 01QG87164, NGFN Plus 01 GS 08152, 01 GS 08159
Funding program : -
Funding organization : Bundesministerium für Bildung und Forschung

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Title: Schizophrenia Bulletin
  Other : Schizophr. Bull.
Source Genre: Journal
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Publ. Info: Rockville, MD : U.S. Dept. of Health, Education and Welfare, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration
Pages: - Volume / Issue: 46 (6) Sequence Number: - Start / End Page: 1535 - 1546 Identifier: ISSN: 0586-7614
CoNE: https://pure.mpg.de/cone/journals/resource/954925532975