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

Sanne Wulff; Mette Ødegaard Nielsen; Egill Rostrup; Claus Svarer; Lars Thorbjørn Jensen; Lars Pinborg; Birte Yding Glenthøj

doi:10.1017/s0033291718004099

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

Sanne Wulff, Mette Ødegaard Nielsen^*, Egill Rostrup, Claus Svarer, Lars Thorbjørn Jensen, Lars Pinborg, Birte Yding Glenthøj

^*Corresponding author for this work

Department of Clinical Medicine

6 Citations (Scopus)

Abstract

BackgroundPsychotic 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.MethodsTwenty-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.ResultsIn 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).ConclusionThe 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.

Original language	English
Journal	Psychological Medicine
ISSN	0033-2917
DOIs	https://doi.org/10.1017/s0033291718004099
Publication status	Published - 2019

Keywords

Antipsychotic
dopamine
fMRI
reward
schizophrenia
SPECT

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10.1017/s0033291718004099

Cite this

@article{d79fa14053ba48f58f29ac70764aa3e0,

title = "The relation between dopamine D2 receptor blockade and the brain reward system: A longitudinal study of first-episode schizophrenia patients",

abstract = "BackgroundPsychotic 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-na{\"i}ve first-episode schizophrenia patients.MethodsTwenty-two antipsychotic-na{\"i}ve 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.ResultsIn 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).ConclusionThe 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 = "Antipsychotic, dopamine, fMRI, reward, schizophrenia, SPECT",

author = "Sanne Wulff and Nielsen, {Mette {\O}degaard} and Egill Rostrup and Claus Svarer and Jensen, {Lars Thorbj{\o}rn} and Lars Pinborg and Glenth{\o}j, {Birte Yding}",

year = "2019",

doi = "10.1017/s0033291718004099",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

TY - JOUR

T1 - The relation between dopamine D2 receptor blockade and the brain reward system

T2 - A longitudinal study of first-episode schizophrenia patients

AU - Wulff, Sanne

AU - Nielsen, Mette Ødegaard

AU - Rostrup, Egill

AU - Svarer, Claus

AU - Jensen, Lars Thorbjørn

AU - Pinborg, Lars

AU - Glenthøj, Birte Yding

PY - 2019

Y1 - 2019

N2 - BackgroundPsychotic 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.MethodsTwenty-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.ResultsIn 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).ConclusionThe 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.

AB - BackgroundPsychotic 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.MethodsTwenty-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.ResultsIn 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).ConclusionThe 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.

KW - Antipsychotic

KW - dopamine

KW - fMRI

KW - reward

KW - schizophrenia

KW - SPECT

U2 - 10.1017/s0033291718004099

DO - 10.1017/s0033291718004099

M3 - Journal article

C2 - 30642415

AN - SCOPUS:85060046888

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine