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

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.

SUBMITTER: Ermakova AO

PROVIDER: S-EPMC6006166 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Ermakova Anna O AO Knolle Franziska F Justicia Azucena A Bullmore Edward T ET Jones Peter B PB Robbins Trevor W TW Fletcher Paul C PC Murray Graham K GK

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180405 8

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 varyi ...[more]

PMID: 29748629

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Project description:BackgroundThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated.MethodsUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsPerceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.ConclusionsThese findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain-behavior relationships vary as a function of development.

Dataset Information

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

Publications

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

Similar Datasets

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