In Vivo 31P Spectroscopy and MRI in ADHD

描述(申请人提供)：神经发育障碍，注意缺陷多动障碍(ADHD)，是最常见的儿童行为障碍之一，影响大约3%至9%的人口。ADHD首先在注意力不集中、多动和冲动的儿童中被诊断出来。大量的遗传学、神经影像、分子和神经化学研究对ADHD的神经病理生理学有了更深入的了解；然而，关于ADHD仍有许多悬而未决的问题。在体磷磁共振波谱(31P MRS)是一种非侵入性技术，可以直接评估膜磷脂(MPL)和高能磷酸盐在多个局部脑区的代谢。初步结果显示，与对照组相比，ADHD儿童和青少年注意神经网络[前额叶(PF)、基底节和颞上]相关区域的MPL代谢和高能磷酸盐利用发生了显著变化。与正常的神经发育数据相比，这些变化似乎偏离了自然发生的变化。此外，MPL代谢物与ADHD和对照组受试者的PF和顶叶下部的持续注意表现相关。总而言之，ADHD的这些生化变化提供了证据，表明负责注意力功能的区域存在缺陷，这是由于神经元过程和突触发育不足所致。然而，目前尚不清楚这些改变是否具有非进行性行为，因此也会出现在药物治疗之前相对较早的疾病阶段。因此，这项研究的目的是使用多体素采集方案，在32名服用药物的ADHD儿童和32名年龄和性别匹配的健康对照组中，横断面评估7个不同脑区的31P代谢物差异。还将获得总灰质和白质体积以及关键结构的MRI结构测量结果。此外，每个左右大脑感兴趣区域的代谢物水平将与同一区域的灰质、白质和脑脊液的百分比以及结构测量相关联。虽然人们不会期望从这项研究的发现中直接出现新的治疗方法，但对ADHD分子/生化知识的增加将支撑未来为ADHD开发特定的躯体治疗方法的努力。

DESCRIPTION (provided by applicant): The neurodevelopmental disorder, attention deficit hyperactive disorder (ADHD), is one of the most prevalent childhood behavioral disorders, affecting approximately 3% to 9% of the population. ADHD is first diagnosed in children with symptoms of inattention, hyperactivity and impulsivity. Numerous genetic, neuroimaging, molecular and neurochemical studies have provided a greater understanding of the neuropathophysiology of ADHD; however, there are many unanswered questions about ADHD. In vivo phosphorus magnetic resonance spectroscopy (31P MRS) is a noninvasive technique that can directly assess the metabolism of membrane phospholipids (MPL) and high-energy phosphates in multiple, localized brain regions. Preliminary results show significant alterations in MPL metabolism and high-energy phosphate utilization in regions associated with the neural networks of attention [prefrontal (PF), basal ganglia and superior temporal] of children and adolescents with ADHD compared to controls. When compared to normal neurodevelopmental data, these alterations appear to deviate from the naturally occuring changes. Additionally, MPL metabolites correlated with sustained attention performance in the PF and inferior parietal of both ADHD and control subjects. In all, these biochemical alterations in ADHD provide evidence of a deficit in regions responsible for the function of attention that are due to underdeveloped neuronal processes and synapses. It is, however, unclear if these alterations have a non-progressive behavior and as a result also would be present at a relatively earlier stage of illness prior to medication treatment. Therefore, the purpose of this study is to assess cross-sectionally in vivo 31P metabolite differences from 7 different brain regions between 32 medication-naive children with ADHD and 32 healthy age- and gender-matched controls, using a multi-voxel acquisition schemes. MRI structural measurements of total grey and white matter volumes and of key structures also will be obtained. Additionally, metabolite levels for each right and left brain region of interest will be correlated with percent grey and white matter and cerebral spinal fluid in the same region and with the structural measurements. While one would not expect new treatments to emerge directly from this study's findings, the increased molecular/biochemical knowledge of ADHD will anchor future efforts to develop specific somatic treatments for ADHD.