Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study.,Translational Psychiatry

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Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-15 , DOI: 10.1038/s41398-019-0619-y
Christine Ulke ₁ , Michael Rullmann ₂ , Jue Huang ₁ , Julia Luthardt ₂ , Georg-Alexander Becker ₂ , Marianne Patt ₂ , Philipp M Meyer ₂ , Solveig Tiepolt ₂ , Swen Hesse ₂ , Osama Sabri ₂ , Maria Strauß ₁

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The norepinephrine transporter (NET) has been suggested to play a critical role in attention-deficit/hyperactivity disorder (ADHD). In this prospective controlled study we tested the a-priori-hypothesis that central NET availability is altered in adult ADHD patients compared to healthy controls. Study participants underwent single positron emission tomography-magnetic resonance imaging (PET-MRI). MRI sequences included high resolution T1-MPRAGE data for regions of interest (ROI) delineation and voxel-based morphometry (VBM) and T2-weighted fluid-attenuated inversion-recovery for detection and exclusion of pathological abnormalities. NET availability was assessed by NET-selective (S,S)-O-[11C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with two constraints (MRTM2; reference region: occipital cortex). VBM analysis revealed no difference in local distribution of gray matter between the 20 ADHD patients (9 females, age 31.8 ± 7.9 years, 488 ± 8 MBq injected activity) and the 20 age-matched and sex-matched control participants (9 females, age 32.3 ± 7.9 years, 472 ± 72 MBq). In mixed-model repeated-measures analysis with NET availability as dependent and ROI as repeated measure we found a significant main effect group in fronto-parietal-thalamic-cerebellar regions (regions on the right: F1,25 = 12.30, p = .002; regions on the left: F1,41 = 6.80, p = .013) indicating a reduced NET availability in ADHD patients. None of the other investigated brain regions yielded significant differences in NET availability between groups after applying a Benjamini-Hochberg correction at a significance level of 0.05. Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.

中文翻译：

成人注意力缺陷/多动障碍与右注意力网络中去甲肾上腺素转运蛋白可用性降低有关：(S,S)-O-[11C]甲基瑞波西汀正电子发射断层扫描研究。

去甲肾上腺素转运蛋白（NET）被认为在注意力缺陷/多动障碍（ADHD）中发挥着关键作用。在这项前瞻性对照研究中，我们测试了先验假设，即与健康对照相比，成年 ADHD 患者的中枢 NET 可用性发生了改变。研究参与者接受了单正电子发射断层扫描-磁共振成像（PET-MRI）。MRI 序列包括用于感兴趣区域 (ROI) 描绘的高分辨率 T1-MPRAGE 数据和基于体素的形态测量 (VBM) 以及用于检测和排除病理异常的 T2 加权流体衰减反转恢复。通过 NET 选择性 (S,S)-O-[11C]甲基瑞波西汀评估 NET 可用性；区域分布体积比 (DVR) 是根据个体 PET-MRI 数据共同配准和具有两个约束的多线性参考组织模型（MRTM2；参考区域：枕叶皮质）计算的。VBM 分析显示，20 名 ADHD 患者（9 名女性，年龄 31.8 ± 7.9 岁，488 ± 8 MBq 注射活动）和 20 名年龄匹配和性别匹配的对照参与者（9 名女性，年龄32.3 ± 7.9 年，472 ± 72 MBq）。在混合模型重复测量分析中，以 NET 可用性作为依赖项，以 ROI 作为重复测量，我们发现额顶叶丘脑小脑区域有一个显着的主效应组（右侧区域：F1,25 = 12.30，p = .002 ；左侧区域：F1,41 = 6.80，p = .013）表明 ADHD 患者的 NET 可用性降低。在应用显着性水平为 0.05 的 Benjamini-Hochberg 校正后，其他研究的大脑区域均未产生组间 NET 可用性的显着差异。总的来说，我们的研究结果证明了 NET 可用性在成人 ADHD 中的病理生理学参与。

更新日期：2019-11-17

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