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, Tetsuya Suhara

研究成果: Article査読

18 被引用数 (Scopus)

抄録

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, [ 11 C]raclopride and [ 11 C]MNPA, were employed to quantify total dopamine D2 receptor and D2High, respectively, in the striatum by measuring their binding potentials. Binding potential values of [ 11 C] raclopride and [ 11 C]MNPA and the binding potential ratio of [ 11 C]MNPA to [ 11 C]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 [ 11 C] raclopride or [ 11 C]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.

本文言語English
ページ(範囲)928-935
ページ数8
ジャーナルInternational Journal of Neuropsychopharmacology
20
11
DOI
出版ステータスPublished - 2017 11月 1
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 精神医学および精神衛生
  • 薬理学(医学)

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