Abnormal reward prediction-error signalling in antipsychotic naive individuals with first-episode psychosis or clinical risk for psychosis.
Authors
Justicia, Azucena
Publication Date
2018-07Journal Title
Neuropsychopharmacology
ISSN
0893-133X
Publisher
Springer Science and Business Media LLC
Volume
43
Issue
8
Pages
1691-1699
Language
eng
Type
Article
This Version
VoR
Previous Version(s)
Physical Medium
Print-Electronic
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Ermakova, A. O., Knolle, F., Justicia, A., Bullmore, E., Jones, P., Robbins, T., Fletcher, P., & et al. (2018). Abnormal reward prediction-error signalling in antipsychotic naive individuals with first-episode psychosis or clinical risk for psychosis.. Neuropsychopharmacology, 43 (8), 1691-1699. https://doi.org/10.1038/s41386-018-0056-2
Abstract
Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.
Keywords
Brain, Neural Pathways, Humans, Magnetic Resonance Imaging, Brain Mapping, Risk, Reward, Psychotic Disorders, Female, Male, Young Adult, Anticipation, Psychological, Prodromal Symptoms
Sponsorship
Medical Research Council (G1000183)
Wellcome Trust (093875/Z/10/Z)
Wellcome Trust (095692/Z/11/Z)
Medical Research Council (G0701911)
Medical Research Council (G0001354)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1038/s41386-018-0056-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283629
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