In Vivo 31P Spectroscopy and MRI in ADHD

体内 31P 光谱和 MRI 在 ADHD 中的应用

• 批准号: 6783459
• 负责人: Jeffrey A Stanley
• 金额: $ 15.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-28 至 2005-03-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783459
• 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，注意缺陷多动障碍（ADHD），是最常见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，多动和冲动的症状。许多遗传学、神经影像学、分子和神经化学研究已经对ADHD的神经病理生理学有了更深入的了解;然而，关于ADHD还有许多未解答的问题。体内磷磁共振波谱（31 P MRS）是一种非侵入性技术，可以直接评估多个局部脑区膜磷脂（MPL）和高能磷酸盐的代谢。初步结果显示，与对照组相比，ADHD儿童和青少年的MPL代谢和高能磷酸盐利用与注意力神经网络相关的区域[前额叶（PF），基底神经节和上级颞叶]发生了显着变化。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代谢产物与ADHD和对照组的PF和下顶叶的持续注意力表现相关。总之，ADHD患者的这些生化改变提供了证据，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，因此也会在药物治疗前的相对早期阶段出现。因此，本研究的目的是使用多体素采集方案，评估32名未接受过药物治疗的ADHD儿童和32名健康年龄和性别匹配的对照组之间7个不同脑区的横截面体内31 P代谢物差异。还将获得总灰质和白色物质体积以及关键结构的MRI结构测量值。此外，每个感兴趣的右脑和左脑区域的代谢物水平将与同一区域中的灰质和白色物质百分比以及脑脊液以及结构测量值相关。虽然人们不会期望新的治疗方法直接从这项研究的发现中出现，但ADHD的分子/生物化学知识的增加将锚未来的努力，以开发针对ADHD的特定体细胞治疗方法。