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

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.

journal_name

Psychol Med

journal_title

Psychological medicine

authors

Vanes LD,Mouchlianitis E,Collier T,Averbeck BB,Shergill SS

doi

10.1017/S0033291718000041

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

2418-2427

issue

eissn

0033-2917

issn

1469-8978

pii

S0033291718000041

journal_volume

pub_type

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