Magnetic Resonance Spectroscopy in Affective Illness

磁共振波谱检查在情感疾病中的应用

• 批准号: 6649156
• 负责人: CONSTANCE M MOORE
• 金额: $ 13.76万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6649156
• 关键词: antidepressants; behavioral /social science research tag; bioimaging /biomedical imaging; bipolar depression; caudate nucleus; cingulate gyrus; clinical research; ethanolamines; human subject; human therapy evaluation; lithium; longitudinal human study; major depression; mental disorder chemotherapy; mood disorders; neuroimaging; neuropsychology; nuclear magnetic resonance spectroscopy; nucleoside triphosphate; phosphatidylcholines; phosphoric ester; prognosis

The specific aim of this application is to afford the applicant, a physicist, the opportunity to become an independent researcher applying magnetic resonance spectroscopy (MRS) in affective disorders. Two components are proposed to accomplish this: formal academic training in psychology and neuroscience; and two research projects. There is an established literature that suggests the pathophysiology of affective illness may lie in irregularities in second messenger and signal transduction pathways; in particular the phosphatidylcholine (PtdCho) and phosphatidylinositol (PtdIno) cycles. Elements of the PthCho and PtdIno cycles are detectable using proton (1 H) and phosphorous (31 P) MRS, in particular choline containing compounds (Cho), myo-Inositol containing compounds (Ino), phosphomonoesters (PME), phosphodiesters (PDE) and the nucleotide triphosphates (NTPs). Over the five year course of the study 35 subjects with Major Depressive Disorder (MD), 35 subjects with Bipolar I Disorder (BD) and 20 comparison subjects (NC) will be recruited. A priori regions of interest are the anterior cingulate gyrus and the caudate nuclei since functional neuroimaging studies have noted mood state dependent alterations in metabolic activity in these regions and preliminary MRS data from these brain regions have demonstrated mood-state, medication, and diagnosis- dependent alterations in Cho, Ino, beta-NTP and PME. In the first two years of funding subjects will be examined using proton echo planar spectroscopic imaging (PEPSI) at 1.5 T. For the final three years of funding subjects will be examined using 1H decoupled 31P MRSI at 4.0 T. The use of PEPSI at 1.5 T and 1H decoupled 31P MRSI at 4.0 T will allow for the acquisition of spectra from smaller regions of interest, such as the anterior cingulate and the caudate, than is possible with older techniques. In addition, PEPSI affords a time advantage which allows for the absolute quantification of the metabolites detected. All subjects will be examined on two occasions six weeks apart and the following hypotheses will be tested: Increased right cingulate cortex Cho will be associated with depression. A decrease in the left cingulate cortex Cho will occur as a result of antidepressant treatment. Decreased right cingulate cortex Ino will be associated with depression. Decreased caudate nucleus beta-NTP will be associated with depression. An increase in caudate nucleus PME will occur as a result of lithium treatment.

本申请的具体目的是为物理学家申请人提供成为在情感障碍中应用磁共振波谱（MRS）的独立研究人员的机会。为了实现这一目标，提出了两个组成部分：心理学和神经科学的正式学术培训；和两个研究项目。有文献表明，情感疾病的病理生理学可能在于第二信使和信号转导途径的异常；特别是磷脂酰胆碱 (PtdCho) 和磷脂酰肌醇 (PtdIno) 循环。 PthCho 和 PtdIno 循环的元素可使用质子 (1 H) 和磷 (31 P) MRS 进行检测，特别是含胆碱的化合物 (Cho)、含肌醇的化合物 (Ino)、磷酸单酯 (PME)、磷酸二酯 (PDE)和三磷酸核苷酸（NTP）。在为期五年的研究过程中，将招募 35 名重度抑郁症 (MD) 受试者、35 名 I 型双相情感障碍 (BD) 受试者和 20 名对照受试者 (NC)。先验感兴趣的区域是前扣带回和尾状核，因为功能神经影像学研究已经注意到这些区域代谢活动的情绪状态依赖性改变，并且来自这些大脑区域的初步 MRS 数据已经证明情绪状态、药物和诊断依赖Cho、Ino、beta-NTP 和 PME 的变化。在资助的前两年，受试者将使用 1.5 T 的质子回波平面光谱成像 (PEPSI) 进行检查。在资助的最后三年，受试者将使用 4.0 T 的 1H 解耦 31P MRSI 进行检查。使用 PEPSI 在 1.5 T 下进行检查。 T 和 1H 解耦 31P MRSI 在 4.0 T 下将允许从较小的感兴趣区域（例如前部）采集光谱与旧技术相比，扣带皮层和尾状核的能力更强。此外，PEPSI 还具有时间优势，可以对检测到的代谢物进行绝对定量。所有受试者将在相隔六周的时间里接受两次检查，并测试以下假设： 右扣带皮层 Cho 增加与抑郁症相关。 抗抑郁药物治疗会导致左扣带皮层 Cho 减少。 右扣带皮层 Ino 减少会与抑郁症相关。 尾状核β-NTP减少与抑郁症有关。 锂治疗会导致尾状核 PME 增加。