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) 是最常见的儿童行为障碍之一，影响约 3% 至 9% 的人口。 ADHD 最初是在有注意力不集中、多动和冲动症状的儿童中被诊断出来的。大量的遗传学、神经影像学、分子和神经化学研究使人们对 ADHD 的神经病理生理学有了更深入的了解。然而，关于多动症还有许多悬而未决的问题。体内磷磁共振波谱（31P MRS）是一种无创技术，可以直接评估多个局部脑区域的膜磷脂（MPL）和高能磷酸盐的代谢。初步结果显示，与对照组相比，患有 ADHD 的儿童和青少年的注意力神经网络 [前额叶 (PF)、基底神经节和颞上叶] 相关区域的 MPL 代谢和高能磷酸盐利用发生了显着变化。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 和对照受试者的 PF 和下顶叶的持续注意力表现相关。总而言之，多动症的这些生化改变提供了负责注意力功能的区域由于神经元过程和突触发育不全而出现缺陷的证据。然而，尚不清楚这些改变是否具有非进行性行为，因此也可能出现在药物治疗之前的疾病相对早期阶段。因此，本研究的目的是使用多体素采集方案，对 32 名未接受药物治疗的 ADHD 儿童和 32 名年龄和性别匹配的健康对照者之间 7 个不同大脑区域的 31P 体内横断面代谢差异进行评估。还将获得总灰质和白质体积以及关键结构的 MRI 结构测量。此外，每个感兴趣的右脑和左脑区域的代谢水平将与同一区域中灰质和白质以及脑脊髓液的百分比以及结构测量值相关。虽然人们不会指望这项研究的结果会直接出现新的治疗方法，但对多动症的分子/生化知识的增加将为未来开发针对多动症的特定躯体治疗方法奠定基础。