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Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia

Published online by Cambridge University Press:  14 February 2018

Lucy D. Vanes ,
Elias Mouchlianitis ,
Tracy Collier ,
Bruno B. Averbeck  and
Sukhi S. Shergill
Lucy D. Vanes*
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, UK
Elias Mouchlianitis
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, UK
Tracy Collier
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, UK
Bruno B. Averbeck
Affiliation:
Unit on Learning and Decision Making, Laboratory of Neuropsychology, NIMH, NIH, Bethesda, MD 20892, USA
Sukhi S. Shergill
Affiliation:
Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, UK
*
Author for correspondence: Lucy D. Vanes, E-mail: [email protected]
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Abstract

Background

The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients.

Methods

In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups.

Results

Patients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate.

Conclusion

TRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism – a glutamatergic mechanism would be a possible candidate.

Keywords

Antipsychoticsdopaminepsychosisprediction errorreinforcement learningreward learningschizophreniatreatment-resistant schizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 14 , October 2018 , pp. 2418 - 2427
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

The first two authors should be regarded as joint first Authors.

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