Classification of schizophrenia-related disorders by multimodal neuroimaging assessments of PDE10A

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17101
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kyoto University (2020-2022); National Institutes for Quantum and Radiological Science and Technology (2019)
• Principal Investigator: Kubota Manabu 京都大学, 医学研究科, 助教 (30760368)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 統合失調症 / ホスホジエステラーゼ / PDE10A / PET / MRS / striatum / cognition / [18F]MNI659

Outline of Final Research Achievements

Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. We performed PET imaging with [18F]MNI-659, a specific PDE10A radioligand, to quantify PDE10A availabilities in in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on the PDE10A radioligand availabilities, indicating higher availabilities in the sensorimotor striatum in patients. The availabilities in this subregion were significantly and negatively correlated with the BACS Tower of London subtest scores in controls but not in patients. Glutamate levels assessed with MRS did not correlate significantly with the availabilities in either group. The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

PDE10Aはドーパミン制御機構を担う細胞内酵素であり、その阻害薬は統合失調症の創薬ターゲットの一つとなっている。しかしこれまで統合失調症患者の生体脳におけるPDE10Aの状態や分布を調べた研究はほとんど存在しなかった。本研究により、統合失調症の病態にPDE10Aの状態変化が関与することが示された。この結果は統合失調症の病態理解および統合失調症をはじめとする精神疾患の新規治療戦略構築に寄与すると考えられる。