Cortical GABA in MDD and Primary Insomnia with Magnetic Resonance Spectroscopy

皮质 GABA 在 MDD 和原发性失眠中的磁共振波谱分析

• 批准号: 8729124
• 负责人: John W Winkelman
• 金额: $ 32.55万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8729124
• 关键词: Affinity; Agonist; Anterior; Arousal; Benzodiazepine Receptor; Biogenic Amines; Brain; Brain imaging; Brain region; Characteristics; Comorbid Insomnia; Creatine; Diagnostic; Disease; Electroencephalography; Etiology; Functional disorder; Glutamates; Grant; Image; Indium; Individual; Lead; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maintenance; Major Depressive Disorder; Measures; Medical; Mental disorders; Modeling; Moods; Neurobiology; Neurons; Neurotransmitters; Occipital lobe; Patients; Physiological; Play; Polysomnography; Prevalence; Primary Insomnia; Protons; Regression Analysis; Relative (related person); Reporting; Research; Role; Sleep; Sleep disturbances; Sleeplessness; Syndrome; System; Testing; Thalamic structure; United States; actigraphy; cingulate cortex; cost; diaries; disturbance in affect; follow-up; frontal lobe; gamma-Aminobutyric Acid; heart rate variability; hypothalamic-pituitary-adrenal axis; in vivo; interest; lifetime risk; neurochemistry; preoptic nucleus; receptor

DESCRIPTION (provided by applicant): Cortical GABA in MDD and Primary Insomnia with Magnetic Resonance Spectroscopy OBJECTIVE: To investigate GABA levels in anterior cingulate (ACC), parieto-occipital (POC) and frontal cortices (FC) in major depressive disorder (MDD) and primary insomnia with proton magnetic resonance spectroscopy imaging (1H MRS). BACKGROUND: The prevalence of MDD as well as its personal and societal costs have motivated over four decades of research into its pathophysiology and neurobiological correlates. Although the preponderance of studies have focused on the role of the biogenic amines and the hypothalamic-pituitary-adrenal (HPA) axis, recent evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA) may play a key role in the pathophysiology of MDD. Supporting this conclusion are recent studies utilizing proton magnetic resonance spectroscopy (1H-MRS), which permits in vivo analysis of brain neurochemistry. Most of these studies concurred in finding reduced GABA levels in multiple brain regions in MDD including the POC, ACC, and the FC. Recently, we utilized 1H-MRS to reveal GABA deficits in subjects with primary insomnia (PI), e.g., insomnia without other accompanying medical or psychiatric disorders. Relative to good sleeper controls, subjects with PI not only had reduced levels of GABA, but within subjects with PI, GABA levels correlated with polysomnographic (PSG) measures of sleep maintenance. The proposed study will test the hypothesis that GABA deficits in MDD in fact reflect the sleep disturbance characteristic of that disorder rather than the mood state per se. METHOD: We plan to perform 1H MRS imaging for GABA/creatine levels in the ACC, POC and FC in 50 subjects with MDD (half of whom will have insomnia and the other half will not), 25 subjects with PI (insomnia without mood disturbance) and 25 control subjects. All subjects will have sleep diaries and actigraphy for 2 weeks prior to their PSG and MRI. The primary endpoint, GABA levels, will be analyzed by repeated measures ANOVA (using linear mixed model) with diagnostic group (4 study groups) as the main effect and the 3 ROIs (POC, ACC, and FC) as repeats. We will also use regression analysis to correlate PSG and sleep diary information, with 1H MRS.

描述（由申请人提供）：MDD中的皮质GABA和具有磁共振光谱的主要失眠目标：研究前扣带回（ACC），前枕骨（POC）和前抑郁症（FC）中的GABA水平（主要抑郁症（MDD）（MDD）（MDD）和初级内部缺陷的priton磁性谱谱（1）（1）。背景：MDD的流行及其个人和社会成本的促进了四十年来研究其病理生理学和神经生物学相关的研究。尽管大量研究集中在生物胺和下丘脑 - 垂体 - 肾上腺（HPA）轴的作用上，但最近的证据表明，神经递质γ-氨基丁酸（GABA）可能在MDD的病理学中起关键作用。支持这一结论的是使用质子磁共振光谱（1H-MR）的最新研究，该研究允许对脑神经化学的体内分析。这些研究大多数同意发现MDD多个大脑区域的GABA水平降低，包括POC，ACC和FC。最近，我们利用1H-MRS揭示了原发性失眠（PI）受试者（例如失眠症）中没有其他伴随的医学或精神疾病的受试者的GABA缺陷。相对于良好的卧铺对照，PI的受试者不仅具有降低的GABA，而且在具有PI的受试者中，GABA水平与多摄影术（PSG）相关的睡眠维持度量相关。拟议的研究将检验以下假设：MDD中的GABA缺陷实际上反映了该疾病的睡眠障碍特征，而不是情绪状态本身。方法：我们计划在50名患有MDD的受试者中对ACC，POC和FC中的GABA/肌酸水平进行1H MRS成像（其中一半将患有失眠，另一半将不会），25名患有PI的受试者（失眠症没有情绪干扰）和25名对照受试者。所有受试者都将在PSG和MRI之前进行2周的睡眠日记和精神分裂症。将通过重复测量方差分析（使用线性混合模型）与诊断组（4个研究组）作为主要效应（主要效应）将主要终点（使用线性混合模型）作为重复分析。我们还将使用回归分析将PSG和睡眠日记信息与1H MRS相关联。