Negative symptoms, striatal dopamine and model-free reward decision-making in schizophrenia
Open accessAbstract
Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments. We hypothesized that in patients with schizophrenia during psychotic remission, impaired influences of both model-based and model-free reward predictions on decision-making (‘reward prediction influence’, RPI) underlie negative symptoms. We focused on psychotic remission, because psychotic symptoms might confound reward-based decision-making. Moreover, we hypothesized that impaired model-based/model-free RPIs depend on alterations of both associative striatum dopamine synthesis and storage (DSS) and executive functioning. Both factors influence RPI in healthy subjects and are typically impaired in schizophrenia. Twenty-five patients with schizophrenia with pronounced negative symptoms during psychotic remission and 24 healthy controls were included in the study. Negative symptom severity was measured by the Positive and Negative Syndrome Scale negative subscale, model-based/model-free RPI by the two-stage decision task, associative striatum DSS by 18F-DOPA positron emission tomography and executive functioning by the symbol coding task. Model-free RPI was selectively reduced in patients and associated with negative symptom severity as well as with reduced associative striatum DSS (in patients only) and executive functions (both in patients and controls). In contrast, model-based RPI was not altered in patients. Results provide evidence for impaired model-free reward prediction influence as a mechanism for negative symptoms in schizophrenia as well as for reduced associative striatum dopamine and executive dysfunction as relevant factors. Data suggest potential treatment targets for patients with schizophrenia and pronounced negative symptoms.
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The literature suggests alterations in the distinct reinforcement learning systems that underlie model-free and model-based decision-making processes in OCD, MDD, and schizophrenia.
“The literature suggests alterations in the distinct reinforcement learning systems that underlie model-free and model-based decision-making processes in OCD, MDD, and schizophrenia. 59,63,69–74”
From Investigating disorder-specific and transdiagnostic alterations in model-based and model-free decision-making (2024) · cites this paper as [59]
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- Authors
- Brandl, F., Knolle, F., Avram, M., Leucht, C., Yakushev, I., Priller, J., Leucht, S., Ziegler, S., Wunderlich, K., & Sorg, C.
- Affiliations
- Technical University of Munich (DE)
- University of Cambridge (GB)
- University of Lübeck (DE)
- King's College London (GB)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Brandl, Felix
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-07-25
- Volume
- 146
- Issue
- 2
- Pages
- 767-777
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W4287218996
- Cited by
- 24
- References
- 87
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 7 · 2023: 4
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Else Kröner Memorial Stipendium
- Hans und Klementia Langmatz Foundation
- European Union’s Horizon 2020 (754462)
- German Federal Ministry of Education and Research (01ER0803)
- German Research Council (SO1336/7)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- schizophrenia, negative symptoms, striatal dopamine, executive dysfunction, reward-based decision-making, 18F-DOPA PET
- MeSH terms
- Dopamine, Humans, Psychotic Disorders, Reward, Schizophrenia, Tomography, X-Ray Computed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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