Journal Article Affinity-states of striatal dopamine D2 receptors in antipsychotic-free patients with schizophrenia

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

Background: Dopamine D2 receptors (D2Rs) 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 ten antipsychotic-naive and one antipsychotic-free individuals, and seventeen healthy controls were investigated. Psychopathology was assessed by Positive and Negative Syndrome Scale (PANSS), and a 5-factor model was used. Two radioligands, [11C]raclopride and [11C]MNPA, were employed to quantify total D2R and D2High, respectively, in the striatum by measuring their binding potential (BPND). BPND values of [11C]raclopride and [11C]MNPA, and in the BPND ratio of [11C]MNPA to [11C]raclopride in the striatal subregions were statistically compared between the two diagnostic groups using multivariate analysis of covariance (MANCOVA) controlling for age, gender, and smoking. Correlations between BPND and PANSS scores were also examined.Results: MANCOVA demonstrated a significant effect of diagnosis (schizophrenia and control) on the BPND ratio (p=0.018), although the effects of diagnosis on both BPND of [11C]raclopride and of [11C]MNPA were not significant. Post-hoc test showed that the BPND ratio was significantly higher in the putamen of patients (p=0.017). PANSS “depressed” factor in patients was positively correlated with BPND 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 D2Rs; and 2) associations between depressive symptoms and amounts of caudate D2Rs in patients with schizophrenia.

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