Journal Article

Affinity States of Striatal Dopamine D2 Receptors in Antipsychotic-Free Patients with Schizophrenia

Manabu Kubota, Tomohisa Nagashima, Harumasa Takano, Fumitoshi Kodaka, Hironobu Fujiwara, Keisuke Takahata, Sho Moriguchi, Yasuyuki Kimura, Makoto Higuchi, Yoshiro Okubo, Hidehiko Takahashi, Hiroshi Ito and Tetsuya Suhara

in International Journal of Neuropsychopharmacology

Published on behalf of International College of Neuropsychopharmacology

Volume 20, issue 11, pages 928-935
ISSN: 1461-1457
Published online July 2017 | e-ISSN: 1469-5111 | DOI: http://dx.doi.org/10.1093/ijnp/pyx063
Affinity States of Striatal Dopamine D2 Receptors in Antipsychotic-Free Patients with Schizophrenia

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  • Clinical Pharmacology and Therapeutics
  • Neurology
  • Psychiatry
  • Neuroscience

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Abstract

Background

Dopamine D2 receptors are reported to have high-affinity (D2High) and low-affinity (D2Low) states. Although an increased proportion of D2High has been demonstrated in animal models of schizophrenia, few clinical studies have investigated this alteration of D2High in schizophrenia in vivo.

Methods

Eleven patients with schizophrenia, including 10 antipsychotic-naive and 1 antipsychotic-free individuals, and 17 healthy controls were investigated. Psychopathology was assessed by Positive and Negative Syndrome Scale, and a 5-factor model was used. Two radioligands, [11C]raclopride and [11C]MNPA, were employed to quantify total dopamine D2 receptor and D2High, respectively, in the striatum by measuring their binding potentials. Binding potential values of [11C]raclopride and [11C]MNPA and the binding potential ratio of [11C]MNPA to [11C]raclopride in the striatal subregions were statistically compared between the 2 diagnostic groups using multivariate analysis of covariance controlling for age, gender, and smoking. Correlations between binding potential and Positive and Negative Syndrome Scale scores were also examined.

Results

Multivariate analysis of covariance demonstrated a significant effect of diagnosis (schizophrenia and control) on the binding potential ratio (P=.018), although the effects of diagnosis on binding potential values obtained with either [11C]raclopride or [11C]MNPA were nonsignificant. Posthoc test showed that the binding potential ratio was significantly higher in the putamen of patients (P=.017). The Positive and Negative Syndrome Scale “depressed” factor in patients was positively correlated with binding potential values of both ligands in the caudate.

Conclusions

The present study indicates the possibilities of: (1) a higher proportion of D2High in the putamen despite unaltered amounts of total dopamine D2 receptors; and (2) associations between depressive symptoms and amounts of caudate dopamine D2 receptors in patients with schizophrenia.

Keywords: PET; [11C]raclopride; [11C]MNPA; striatum; high affinity

Journal Article.  4890 words.  Illustrated.

Subjects: Clinical Pharmacology and Therapeutics ; Neurology ; Psychiatry ; Neuroscience

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