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Abnormal reward prediction error signalling in antipsychotic naïve individuals with first episode psychosis or clinical risk for psychosis

Anna O Ermakova, View ORCID ProfileFranziska Knolle, Azucena Justicia, Edward T Bullmore, Peter B Jones, Trevor W Robbins, Paul C Fletcher, Graham K Murray
doi: https://doi.org/10.1101/214437
Anna O Ermakova
1Department of Psychiatry, University of Cambridge
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
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Franziska Knolle
1Department of Psychiatry, University of Cambridge
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
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  • ORCID record for Franziska Knolle
Azucena Justicia
1Department of Psychiatry, University of Cambridge
3Cambridgeshire and Peterborough NHS Foundation Trust
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Edward T Bullmore
1Department of Psychiatry, University of Cambridge
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
3Cambridgeshire and Peterborough NHS Foundation Trust
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Peter B Jones
1Department of Psychiatry, University of Cambridge
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
3Cambridgeshire and Peterborough NHS Foundation Trust
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Trevor W Robbins
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
4Department of Psychology, University of Cambridge
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Paul C Fletcher
1Department of Psychiatry, University of Cambridge
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
3Cambridgeshire and Peterborough NHS Foundation Trust
5Institute of Metabolic Science, University of Cambridge
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Graham K Murray
1Department of Psychiatry, University of Cambridge
2Behavioural and Clinical Neuroscience Institute, University of Cambridge
3Cambridgeshire and Peterborough NHS Foundation Trust
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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 not known at what stage in 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 the earliest stages of psychosis. We studied patients with first episode psychosis (FEP) and help-seeking individuals at risk for psychosis due to subthreshold 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). Patients with FEP 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 patients with FEP have abnormal meso-cortical signalling of reward prediction errors, whilst 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.

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Posted November 05, 2017.
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Abnormal reward prediction error signalling in antipsychotic naïve individuals with first episode psychosis or clinical risk for psychosis
Anna O Ermakova, Franziska Knolle, Azucena Justicia, Edward T Bullmore, Peter B Jones, Trevor W Robbins, Paul C Fletcher, Graham K Murray
bioRxiv 214437; doi: https://doi.org/10.1101/214437
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Abnormal reward prediction error signalling in antipsychotic naïve individuals with first episode psychosis or clinical risk for psychosis
Anna O Ermakova, Franziska Knolle, Azucena Justicia, Edward T Bullmore, Peter B Jones, Trevor W Robbins, Paul C Fletcher, Graham K Murray
bioRxiv 214437; doi: https://doi.org/10.1101/214437

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