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

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]MNPA; [11C]raclopride; high affinity; striatum.

Figure 1.

A group comparison of binding potential ratio (BP_ND ratio) ([¹¹C](R)-2-CH3O-N-n-propylnorapomorphine ([¹¹C]MNPA) to [¹¹C]raclopride) in striatal subregions. A significant diagnostic effect was found on the BP_ND ratio (P=.018; MANCOVA controlled for age, gender, smoking). Univariate posthoc analysis showed that the BP_ND ratio in the putamen was significantly higher in patients (P=.017). HC, healthy control group; Pt, patient group.

Figure 2.

Scatter plots of binding potential (BP_ND) values against Positive and Negative Syndrome Scale (PANSS) “depressed” factor and linear regressions in the caudate of patients with schizophrenia. PANSS “depressed” factor was significantly and positively correlated with BP_ND of [¹¹C]raclopride (left: Pearson’s r = 0.773, P=.005) and of [¹¹C](R)-2-CH3O-N-n-propylnorapomorphine ([¹¹C]MNPA) (right: r = 0.701, P=.016). Statistical significance threshold: P<.05 for the 3 striatal subregions (Bonferroni correction).