Glutamine and Glutamate in Children and Adolescents with Bipolar Disorder

患有双相情感障碍的儿童和青少年的谷氨酰胺和谷氨酸

基本信息

批准号：
7368663
负责人：
CONSTANCE M MOORE
金额：
$ 28.41万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-11 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7368663
关键词：
16 year old Adolescent Adult Affective Aftercare Age Amino Acids Analysis of Variance Anterior Antidepressive Agents Antipsychotic Agents Biological Markers Bipolar Disorder Brain Child Childhood Computer software Data Development Diagnosis Disease Dose Drug Delivery Systems Evaluation Functional disorder Funding Glutamates Glutamine Intervention Invasive Label Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manic Measurement Measures Mood stabilizers Neurons Neurotransmitters Occipital lobe Pathology Pharmaceutical Preparations Phenotype Physiologic pulse Population Prevalence Protons Pulse taking Range Rate Recruitment Activity Regression Analysis Research Personnel Research Project Grants Risperidone Scanning Staging Symptoms System Technology Testing Tissues Week Work Youth atypical antipsychotic base cingulate cortex day follow-up frontal lobe novel response sex

项目摘要

DESCRIPTION (provided by applicant): Bipolar Disorder (BPD) may be as common among youths as it is among adults. The lifetime prevalence for Bipolar Disorder in adults ranges from 0.6% to 1.1%. Determining biological markers for mania in children with BPD is important in order to further our understanding of the underlying pathology of BPD in children. Significant glutamatergic dysfunction is associated with BPD, and many medications that are effective in the treatment of BPD may do so through engagement at various points in the glutamate neurotransmitter system. In addition, persuasive post-mortem evidence exists of frontal cortex glial and neuronal abnormalities in BPD. These abnormalities may be present in children with BPD. The aims of this study are to 1: establish an association between anterior cingulate cortex (ACC) glutamine and glutamate levels, and mania in children and adolescents with BPD; 2: investigate how the atypical antipsychotic risperidone interacts with ACC glutamine and glutamate in children and adolescents with BPD. We propose to study 60 unmedicated manic children and adolescents with BPD (Bipolar 1 Disorder, the narrow phenotype ; Young Mania Rating Scale (YMRS) > 15) before and after treatment with risperidone. In addition, 60 age and sex matched healthy comparison children (HCS) will participate. Glutamate and glutamine levels will be measured in the ACC and occipital cortex (OC) using Proton Magnetic Resonance Spectroscopy (1H MRS) at 4.0 T. A baseline MRS scan will be acquired from the unmedicated subjects with BPD prior to commencing risperidone treatment. Following 6 weeks of risperidone treatment the subjects with BPD will have a follow up 4.0 T MRS scan. The healthy comparison children will also have two MRS scans 6 weeks apart. Manic symptoms will be assessed prior to each MRS examination using the YMRS. We hypothesize that (a) the mania associated with pediatric BPD is a consequence of glutamatergic abnormalities manifested by reduced ACC glutamine and glutamate and; (b) risperidone will raise ACC glutamine and glutamate levels in children with BPD who are risperidone responders (a 30 % decrease in YMRS). Looking directly at the glutamine and glutamate resonances will allow the assessment of mania biochemically. This project will lay groundwork for further studies to test novel interventions that may be anti-manic agents and suitable for use in a pediatric population. We are proposing to use technology based on MRI to determine if brain frontal cortex levels of the amino acid glutamate, and its precursor glutamine, may be used as potential markers for pediatric mania. In addition, we will look at the effects of the atypical antipsychotic risperidone on glutamate, glutamine and mania in children with bipolar disorder. We believe this work will lay groundwork for further studies to test novel interventions that may be anti-manic agents and suitable for use in a pediatric population.

描述（由申请人提供）：双相情感障碍 (BPD) 在青少年中可能与成人中一样常见。成人双相情感障碍的终生患病率为 0.6% 至 1.1%。确定 BPD 儿童躁狂症的生物标志物对于进一步了解儿童 BPD 的潜在病理学非常重要。严重的谷氨酸能功能障碍与 BPD 相关，许多有效治疗 BPD 的药物可能是通过参与谷氨酸神经递质系统的各个点来实现的。此外，有说服力的尸检证据表明 BPD 中额叶皮层胶质细胞和神经元异常。这些异常可能出现在患有 BPD 的儿童中。本研究的目的是 1：建立前扣带皮层 (ACC) 谷氨酰胺和谷氨酸水平与 BPD 儿童和青少年躁狂症之间的关联；图 2：研究非典型抗精神病药物利培酮如何与 BPD 儿童和青少年中的 ACC 谷氨酰胺和谷氨酸相互作用。我们建议对 60 名患有 BPD（双相 1 型障碍，狭窄表型；青年躁狂评定量表 (YMRS) > 15）的 60 名未接受药物治疗的躁狂儿童和青少年在利培酮治疗前后进行研究。此外，60名年龄和性别匹配的健康对照儿童（HCS）也将参加。将使用质子磁共振波谱 (1H MRS) 在 4.0 T 下测量 ACC 和枕叶皮质 (OC) 中的谷氨酸和谷氨酰胺水平。在开始利培酮治疗之前，将从未接受药物治疗的 BPD 受试者中获取基线 MRS 扫描。利培酮治疗 6 周后，患有 BPD 的受试者将进行后续 4.0 T MRS 扫描。健康对照儿童还将接受两次 MRS 扫描，间隔 6 周。每次 MRS 检查之前将使用 YMRS 评估躁狂症状。我们假设 (a) 与儿科 BPD 相关的躁狂症是谷氨酸能异常的结果，表现为 ACC 谷氨酰胺和谷氨酸减少； (b) 利培酮会提高对利培酮有反应的 BPD 儿童的 ACC 谷氨酰胺和谷氨酸水平（YMRS 降低 30%）。直接观察谷氨酰胺和谷氨酸共振可以对躁狂症进行生化评估。该项目将为进一步研究奠定基础，以测试可能是抗躁狂药物并适合儿科人群使用的新型干预措施。我们建议使用基于 MRI 的技术来确定大脑额叶皮层中氨基酸谷氨酸及其前体谷氨酰胺的水平是否可以用作儿科躁狂症的潜在标志物。此外，我们还将研究非典型抗精神病药物利培酮对双相情感障碍儿童的谷氨酸、谷氨酰胺和躁狂症的影响。我们相信这项工作将为进一步的研究奠定基础，以测试可能是抗躁狂药物并适合在儿科人群中使用的新型干预措施。