Striatal dopamine D2/3receptors in medication-naïve schizophrenia: An [123I] IBZM SPECT study

Kao Chin Chen; Yen Kuang Yang; Oliver D. Howes; I. Hui Lee; Tzung Lieh Yeh; Nan Tsing Chiu; Po See Chen; Anthony S. David; Elvira Bramon

doi:10.1017/S0033291720005413

Striatal dopamine D_2/3receptors in medication-naïve schizophrenia: An [¹²³I] IBZM SPECT study

Kao Chin Chen, Yen Kuang Yang^*, Oliver D. Howes, I. Hui Lee, Tzung Lieh Yeh, Nan Tsing Chiu, Po See Chen, Anthony S. David, Elvira Bramon

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Background The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. Methods We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. Result The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI-0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age =-0.01(binding ratio); 95% CI-0.01 to-0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. Conclusions Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

Original language	English
Journal	Psychological Medicine
DOIs	https://doi.org/10.1017/S0033291720005413
Publication status	Accepted/In press - 2021

Keywords

dopamine
dopamine receptor
healthy individual
medication-naïve schizophrenia
single-photon emission tomography (SPECT)
[I] iodobenzamide

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10.1017/S0033291720005413

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@article{df0d08906f1e41cbb9cd8f842451f7cc,

title = "Striatal dopamine D2/3receptors in medication-na{\"i}ve schizophrenia: An [123I] IBZM SPECT study",

abstract = "Background The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. Methods We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. Result The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI-0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age =-0.01(binding ratio); 95% CI-0.01 to-0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. Conclusions Medication-na{\"i}ve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release. ",

keywords = "dopamine, dopamine receptor, healthy individual, medication-na{\"i}ve schizophrenia, single-photon emission tomography (SPECT), [I] iodobenzamide",

author = "Chen, {Kao Chin} and Yang, {Yen Kuang} and Howes, {Oliver D.} and Lee, {I. Hui} and Yeh, {Tzung Lieh} and Chiu, {Nan Tsing} and Chen, {Po See} and David, {Anthony S.} and Elvira Bramon",

year = "2021",

doi = "10.1017/S0033291720005413",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

TY - JOUR

T1 - Striatal dopamine D2/3receptors in medication-naïve schizophrenia

T2 - An [123I] IBZM SPECT study

AU - Chen, Kao Chin

AU - Yang, Yen Kuang

AU - Howes, Oliver D.

AU - Lee, I. Hui

AU - Yeh, Tzung Lieh

AU - Chiu, Nan Tsing

AU - Chen, Po See

AU - David, Anthony S.

AU - Bramon, Elvira

PY - 2021

Y1 - 2021

N2 - Background The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. Methods We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. Result The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI-0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age =-0.01(binding ratio); 95% CI-0.01 to-0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. Conclusions Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

AB - Background The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. Methods We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. Result The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI-0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age =-0.01(binding ratio); 95% CI-0.01 to-0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. Conclusions Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

KW - dopamine

KW - dopamine receptor

KW - healthy individual

KW - medication-naïve schizophrenia

KW - single-photon emission tomography (SPECT)

KW - [I] iodobenzamide

UR - http://www.scopus.com/inward/record.url?scp=85102268619&partnerID=8YFLogxK

U2 - 10.1017/S0033291720005413

DO - 10.1017/S0033291720005413

M3 - Article

AN - SCOPUS:85102268619

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Striatal dopamine D_2/3receptors in medication-naïve schizophrenia: An [¹²³I] IBZM SPECT study

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Keywords

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