The relationship between excitement symptom severity and extrastriatal dopamine D2/3 receptor availability in patients with schizophrenia: a high-resolution PET study with [18F]fallypride
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The purpose of this study was to investigate the relationship between specific symptom severity and D2/3 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 D2/3 receptor availability, the binding potential with respect to non-displaceable compartment (BPND) was derived using the simplified reference tissue model. The BPND 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 BPND in the insula. The equivalent dose of antipsychotics was not significantly correlated with PANSS factor scores or regional BPND values. The voxel-based analysis also revealed a significant positive association between the PANSS excitement factor and the [18F]fallypride BPND in the insula. The present study revealed a significant association between excitement symptom severity and D2/3 receptor availability in the insula in schizophrenia, suggesting a possible important role of D2/3 receptor-mediated neurotransmission in the insula and related limbic system in the pathophysiology of this specific symptom cluster.
KeywordsExtrastriatal D2/3 receptor Excitement symptom [18F]fallypride High-resolution PET Insula Schizophrenia
This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2016M3C7A1914451) and by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (number: HI14C2750). This research was also supported by the Gachon University Research Fund of 2015 (number: GCU-2015-5031).
Compliance with ethical standards
The study protocol was approved by the institutional review board of the Gachon University Gil Medical Center, and all procedures used in the study were conducted in accordance with international ethical standard, Declaration of Helsinki. All participants gave their written informed consent prior to their inclusion in the study.
Conflict of interest
The authors declare that they have no conflicts of interest.
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