In Vivo 31P Spectroscopy and MRI in ADHD

描述（由申请人提供）：神经发育障碍，即注意力缺陷多动障碍（ADHD），是最普遍的儿童行为障碍之一，影响约3%至9%的人口。ADHD首先在儿童中被诊断为注意力不集中、多动和冲动。大量的遗传、神经影像学、分子和神经化学研究已经为ADHD的神经病理生理学提供了更好的理解；然而，关于多动症还有许多未解之谜。体内磷磁共振波谱（31P MRS）是一种无创技术，可以直接评估膜磷脂（MPL）和高能磷酸盐在多个局部脑区域的代谢。初步结果显示，与对照组相比，ADHD儿童和青少年的MPL代谢和与注意力神经网络相关的区域（前额叶（PF）、基底神经节和颞上节）的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，这些改变似乎偏离了自然发生的变化。此外，MPL代谢物与多动症和对照组的前前额叶和下顶叶的持续注意表现相关。总之，ADHD患者的这些生化变化提供了证据，证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全造成的。然而，尚不清楚这些改变是否具有非进行性行为，因此也会在药物治疗前的相对较早的疾病阶段出现。因此，本研究的目的是使用多体素采集方案，评估32名未接受药物治疗的ADHD儿童与32名年龄和性别匹配的健康对照组之间7个不同脑区体内31P代谢物的横断面差异。脑灰质和白质总体积以及关键结构的MRI结构测量也将得到。此外，每个感兴趣的左右脑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结果中直接出现新的治疗方法，但增加的ADHD分子/生化知识将为未来开发针对ADHD的特定躯体治疗奠定基础。

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.