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The relation between dopamine D2 receptor blockade and the brain reward system: a longitudinal study of first-episode schizophrenia patients

Published online by Cambridge University Press:  15 January 2019

Sanne Wulff ,
Mette Ødegaard Nielsen Open the ORCID record for Mette Ødegaard Nielsen [Opens in a new window] ,
Egill Rostrup ,
Claus Svarer ,
Lars Thorbjørn Jensen ,
Lars Pinborg  and
Birte Yding Glenthøj
Sanne Wulff
Affiliation:
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
Mette Ødegaard Nielsen*
Affiliation:
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark
Egill Rostrup
Affiliation:
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Physiology, Functional Imaging Unit, Nuclear Medicine and PET, Rigshospitalet Glostrup, University of Copenhagen, København, Denmark
Claus Svarer
Affiliation:
Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, København, Denmark
Lars Thorbjørn Jensen
Affiliation:
Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark
Lars Pinborg
Affiliation:
Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, København, Denmark
Birte Yding Glenthøj
Affiliation:
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark
*
Author for correspondence: Mette Ødegaard Nielsen, E-mail: [email protected]
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Abstract

Background

Psychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.

Methods

Twenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.

Results

In line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = −0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).

Conclusion

The results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.

Keywords

AntipsychoticdopaminefMRIrewardschizophreniaSPECT
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 2 , January 2020 , pp. 220 - 228
Copyright
Copyright © Cambridge University Press 2019

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Footnotes

*

Contributed equally to the study.

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