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Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis

Howes, OD; Hird, EJ; Adams, RA; Corlett, PR; McGuire, P; (2020) Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis. Biological Psychiatry , 88 (4) pp. 304-314. 10.1016/j.biopsych.2020.03.012. Green open access

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Abstract

The aberrant salience hypothesis proposes that striatal dopamine dysregulation causes misattribution of salience to irrelevant stimuli leading to psychosis. Recently, new lines of preclinical evidence on information coding by subcortical dopamine coupled with computational models of the brain's ability to predict and make inferences about the world (predictive processing) provide a new perspective on this hypothesis. Here we review these and summarise the evidence for dopamine dysfunction, reward processing and salience abnormalities in people at clinical risk of psychosis (CHR) relative to findings in patients with psychosis. This identifies consistent evidence for dysregulated subcortical dopamine function in CHR, but also indicates a number of areas where neurobiological processes are different in CHR subjects relative to patients with psychosis, particularly in reward processing. We then consider how predictive processing models may explain psychotic symptoms in terms of alterations in prediction error and precision signalling using Bayesian approaches. We also review the potential role of environmental risk factors, particularly early adverse life experiences, in influencing the prior expectations that individuals have about their world in terms of computational models of the progression from being at CHR to frank psychosis. We identify a number of key outstanding questions, including the relative roles of prediction error or precision signalling in the development of symptoms, and the mechanism underlying dopamine dysfunction. Finally, we discuss how the integration of computational psychiatry with biological investigation may inform the treatment for people at CHR of psychosis.

Type: Article
Title: Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biopsych.2020.03.012
Publisher version: https://doi.org/10.1016/j.biopsych.2020.03.012
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: psychosis; schizophrenia; prodrome; risk; computational psychiatry; imaging
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10095101
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