Alterations of striatal phosphodiesterase 10 A and their association with recurrence rate in bipolar I disorder.

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-02 DOI:10.1038/s41398-024-03107-3
Yasunori Sano, Yasuharu Yamamoto, Manabu Kubota, Sho Moriguchi, Kiwamu Matsuoka, Shin Kurose, Kenji Tagai, Hironobu Endo, Bun Yamagata, Hisaomi Suzuki, Ryosuke Tarumi, Kie Nomoto, Yuhei Takado, Kazunori Kawamura, Ming-Rong Zhang, Hajime Tabuchi, Masaru Mimura, Hiroyuki Uchida, Makoto Higuchi, Keisuke Takahata
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Abstract

Phosphodiesterase 10 A (PDE10A), a pivotal element of the second messenger signaling downstream of the dopamine receptor stimulation, is conceived to be crucially involved in the mood instability of bipolar I disorder (BD-I) as a primary causal factor or in response to dysregulated dopaminergic tone. We aimed to determine whether striatal PDE10A availability is altered in patients with BD-I and assessed its relationship with the clinical characteristics of BD-I. This case-control study used positron emission tomography (PET) with 2-(2-(3-(4-(2-[18F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659), a radioligand that binds to PDE10A, to examine the alterations of the striatal PDE10A availability in the living brains of individuals with BD-I and their association with the clinical characteristics of BD-I. [18F]MNI-659 PET data were acquired from 25 patients with BD-I and 27 age- and sex-matched healthy controls. Patients with BD-I had significantly lower PDE10A availability than controls in the executive (F = 8.86; P = 0.005) and sensorimotor (F = 6.13; P = 0.017) subregions of the striatum. Lower PDE10A availability in the executive subregion was significantly associated with a higher frequency of mood episodes in patients with BD-I (r = -0.546; P = 0.007). This study provides the first evidence of altered PDE10A availability in patients with BD-I. Lower PDE10A availability in the executive subregion of the striatum is associated with an increased recurrence risk, suggesting that PDE10A may prevent BD-I relapse. Further studies are required to elucidate the role of PDE10A in BD-I pathophysiology and explore its potential as a treatment target.

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纹状体磷酸二酯酶10 A的变化及其与双相情感障碍I复发率的关系
磷酸二酯酶10 A(PDE10A)是多巴胺受体刺激下游第二信使信号转导的关键因素,被认为是双相情感障碍(BD-I)情绪不稳定的主要诱因或多巴胺能调节失调的反应。我们旨在确定 BD-I 患者纹状体 PDE10A 的可用性是否发生改变,并评估其与 BD-I 临床特征的关系。这项病例对照研究采用了正电子发射断层扫描(PET)技术,检测 2-(2-(3-(4-(2-[18F]氟乙氧基)苯基)-7-甲基-4-氧代-3,4-二氢喹唑啉-2-基)乙基)-4-异丙氧基异吲哚啉-1,3-二酮([18F]MNI-659)、MNI-659 是一种能与 PDE10A 结合的放射性配体,用于研究 BD-I 患者活体大脑纹状体 PDE10A 供应的改变及其与 BD-I 临床特征的关系。[18F]MNI-659正电子发射计算机断层扫描数据来自25名BD-Ⅰ患者和27名年龄和性别匹配的健康对照者。在纹状体的执行(F = 8.86; P = 0.005)和感觉运动(F = 6.13; P = 0.017)亚区,BD-Ⅰ患者的PDE10A可用性明显低于对照组。执行亚区较低的 PDE10A 可用性与 BD-I 患者较高的情绪发作频率显著相关(r = -0.546;P = 0.007)。这项研究首次提供了 BD-I 患者 PDE10A 可利用率发生改变的证据。纹状体执行亚区较低的 PDE10A 可用性与复发风险的增加有关,这表明 PDE10A 可预防 BD-I 复发。要阐明 PDE10A 在 BD-I 病理生理学中的作用并探索其作为治疗靶点的潜力,还需要进一步的研究。
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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