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Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels

Published online by Cambridge University Press:  26 August 2021

Karen Tangmose*
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Egill Rostrup
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark
Kirsten B Bojesen
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark
Anne Sigvard
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Kasper Jessen
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark
Louise Baruël Johansen
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark
Birte Y. Glenthøj
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Mette Ødegaard Nielsen
Affiliation:
Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
*
Author for correspondence: Karen Tangmose, E-mail: karen.tangmose@regionh.dk

Abstract

Background

Aberrant anticipation of motivational salient events and processing of outcome evaluation in striatal and prefrontal regions have been suggested to underlie psychosis. Altered glutamate levels have likewise been linked to schizophrenia. Glutamatergic abnormalities may affect the processing of motivational salience and outcome evaluation. It remains unresolved, whether glutamatergic dysfunction is associated with the coding of motivational salience and outcome evaluation in antipsychotic-naïve patients with first-episode psychosis.

Methods

Fifty-one antipsychotic-naïve patients with first-episode psychosis (22 ± 5.2 years, female/male: 31/20) and 52 healthy controls (HC) matched on age, sex, and parental education underwent functional magnetic resonance imaging and magnetic resonance spectroscopy (3T) in one session. Brain responses to motivational salience and negative outcome evaluation (NOE) were examined using a monetary incentive delay task. Glutamate levels were estimated in the left thalamus and anterior cingulate cortex using LCModel.

Results

Patients displayed a positive signal change to NOE in the caudate (p = 0.001) and dorsolateral prefrontal cortex (DLPFC; p = 0.003) compared to HC. No group difference was observed in motivational salience or in levels of glutamate. There was a different association between NOE signal in the caudate and DLPFC and thalamic glutamate levels in patients and HC due to a negative correlation in patients (caudate: p = 0.004, DLPFC: p = 0.005) that was not seen in HC.

Conclusions

Our findings confirm prior findings of abnormal outcome evaluation as a part of the pathophysiology of schizophrenia. The results also suggest a possible link between thalamic glutamate and NOE signaling in patients with first-episode psychosis.

Type
Original Article
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels
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Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels
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Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels
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