The relationship between excitement symptom severity and extrastriatal dopamine D_2/3 receptor availability in...

The purpose of this study was to investigate the relationship between specific symptom severity and D_2/3 receptor availability in extrastriatal regions in outpatients with schizophrenia to shed light on the role of extrastriatal dopaminergic neurotransmission in the pathophysiology of symptoms of schizophrenia. Sixteen schizophrenia patients receiving relatively low-dose maintenance atypical antipsychotics and seventeen healthy controls underwent 3-Tesla magnetic resonance imaging and high-resolution positron emission tomography with [¹⁸F]fallypride. For D_2/3 receptor availability, the binding potential with respect to non-displaceable compartment (BP_ND) was derived using the simplified reference tissue model. The BP_ND values were lower in patients on antipsychotic treatment than in controls across all regions with large effect sizes (1.03-1.42). The regions with the largest effect size were the substantia nigra, amygdala, and insula. Symptoms of schizophrenia were assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). The region of interest-based analysis showed that PANSS excitement factor score had a significant positive correlation with the [¹⁸F]fallypride BP_ND in the insula. The equivalent dose of antipsychotics was not significantly correlated with PANSS factor scores or regional BP_ND values. The voxel-based analysis also revealed a significant positive association between the PANSS excitement factor and the [¹⁸F]fallypride BP_ND in the insula. The present study revealed a significant association between excitement symptom severity and D_2/3 receptor availability in the insula in schizophrenia, suggesting a possible important role of D_2/3 receptor-mediated neurotransmission in the insula and related limbic system in the pathophysiology of this specific symptom cluster.