Reinforcement learning as an intermediate phenotype in psychosis? Deficits sensitive to illness stage but not associated with polygenic risk of schizophrenia in the general population
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Abstract
BACKGROUND: Schizophrenia is a complex disorder in which the causal relations between risk genes and observed clinical symptoms are not well understood and the explanatory gap is too wide to be clarified without considering an intermediary level. Thus, we aimed to test the hypothesis of a pathway from molecular polygenic influence to clinical presentation occurring via deficits in reinforcement learning. METHODS: We administered a reinforcement learning task (Go/NoGo) that measures reinforcement learning and the effect of Pavlovian bias on decision making. We modelled the behavioural data with a hierarchical Bayesian approach (hBayesDM) to decompose task performance into its underlying learning mechanisms. Study 1 included controls (n = 29, F|M = 0.81), At Risk Mental State for psychosis (ARMS, n = 23, F|M = 0.35) and FEP (First-episode psychosis, n = 26, F|M = 0.18). Study 2 included healthy adolescents (n = 735, F|M = 1.06), 390 of whom had their polygenic risk scores for schizophrenia (PRSs) calculated. RESULTS: Patients with FEP showed significant impairments in overriding Pavlovian conflict, a lower learning rate and a lower sensitivity to both reward and punishment. Less widespread deficits were observed in ARMS. PRSs did not significantly predict performance on the task in the general population, which only partially correlated with measures of psychopathology. CONCLUSIONS: Reinforcement learning deficits are observed in first episode psychosis and, to some extent, in those at clinical risk for psychosis, and were not predicted by molecular genetic risk for schizophrenia in healthy individuals. The study does not support the role of reinforcement learning as an intermediate phenotype in psychosis.
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Insensitivity to reward has been shown across all stages of schizophrenia and has been associated with negative symptoms, especially anhedonia, and cognitive deficits.
“Insensitivity to reward has been shown across all stages of schizophrenia and has been associated with negative symptoms, especially anhedonia, and cognitive deficits.55,61,119,120”
From Investigating disorder-specific and transdiagnostic alterations in model-based and model-free decision-making (2024) · cites this paper as [55]
Previous work indicated clear differences in the parameters when using group-specific versus group-general priors.
“Previous work indicated clear differences in the parameters when using group-specific versus group-general priors.55,130”
From Investigating disorder-specific and transdiagnostic alterations in model-based and model-free decision-making (2024) · cites this paper as [55]
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- Authors
- Montagnese, M., Knolle, F., Haarsma, J., Griffin, J. D., Richards, A., Vertes, P. E., Kiddle, B., Fletcher, P. C., Jones, P. B., Owen, M. J., Fonagy, P., Bullmore, E. T., Dolan, R. J., Moutoussis, M., Goodyer, I. M., & Murray, G. K.
- Affiliations
- University of Cambridge (GB)
- National Health Service (GB)
- Cardiff University (GB)
- University College London (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Corresponding author
- Murray, Graham K.
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 222
- Pages
- 389-396
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC7594641
- OpenAlex
- W3018331763
- Cited by
- 26
- References
- 50
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 8 · 2022: 1 · 2021: 5
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- reinforcement learning, endophenotypes
- MeSH terms
- Adolescent, Bayes Theorem, Humans, Phenotype, Psychotic Disorders, Schizophrenia, Multifactorial Inheritance
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