TY - JOUR
T1 - Striatal dopamine D 2/3 receptors 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
N1 - Funding Information:
This research was funded by the National Science Council of Taiwan (NSC 91-2314-B-006-074, NSC 92-2314-B-006-111, NSC 93-2314-B-006-107, NSC 95-2314-B-006-115-MY2, and NSC 99-2314- B-006-019-MY3) and Atomic Energy Council of Taiwan (NSC 91-NU-7-006-002 and NSC 92-NU-7-006-004).
Publisher Copyright:
Copyright © The Author(s), 2021.
PY - 2022/10/8
Y1 - 2022/10/8
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.
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U2 - 10.1017/S0033291720005413
DO - 10.1017/S0033291720005413
M3 - Article
C2 - 33682657
AN - SCOPUS:85102268619
SN - 0033-2917
VL - 52
SP - 3251
EP - 3259
JO - Psychological Medicine
JF - Psychological Medicine
IS - 14
ER -