In Vivo 31P Spectroscopy and MRI in ADHD

体内 31P 光谱和 MRI 在 ADHD 中的应用

• 批准号: 6915702
• 负责人: Jeffrey A Stanley
• 金额: $ 18.77万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-24 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915702
• 关键词: attention deficit disorder; behavior test; biosynthesis; biotransformation; brain morphology; caudate nucleus; cerebrospinal fluid; clinical research; computer program /software; corpus callosums; developmental neurobiology; human subject; magnetic resonance imaging; mathematics; middle childhood (6-11); morphometry; neuropsychological tests; patient oriented research; phospholipids; phosphoric ester; phosphorus metabolism; synapses

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.

描述（由申请人提供）：神经发育障碍，注意力缺陷多动障碍（ADHD）是最普遍的儿童行为障碍之一，影响了大约3％至9％的人群。 ADHD首先在患有注意力不集中，多动症和冲动性症状的儿童中被诊断出。许多遗传，神经影像学，分子和神经化学研究为ADHD的神经病理生理学提供了更深入的了解。但是，关于多动症有许多未解决的问题。体内磷磁共振光谱（31p MRS）是一种无创的技术，可以直接评估多个局部脑区域中膜磷脂（MPL）（MPL）和高能磷酸盐的代谢。初步结果表明，与对照组相比，儿童和青少年在与关注神经网络[前额叶（PF），基底神经节和上等时间]相关的区域中，MPL代谢和高能磷酸盐利用的显着变化。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ADHD和对照组的PF中的持续注意力表现相关。总的来说，ADHD中的这些生化变化提供了导致注意力功能的区域缺陷的证据，这是由于神经元过程欠发达的过程和突触所致。但是，目前尚不清楚这些改变是否具有非促进行为，因此在药物治疗之前的疾病阶段也存在。因此，这项研究的目的是使用多体素习得方案在32名患有ADHD和32名健康年龄和性别匹配的健康和性别匹配的对照组之间的7种不同大脑区域的体内31p代谢物差异评估横截面。还将获得总灰质和白质体积和关键结构的MRI结构测量。此外，每个感兴趣的右脑区域的代谢物水平将与灰色和白质的百分比以及同一区域以及结构测量的百分比以及脑脊髓液相关。虽然人们不会期望直接从这项研究的发现中出现新的治疗方法，但增加的ADHD分子/生化知识将奠定未来的努力，以开发针对ADHD的特定体细胞治疗。