Subtype-specific alterations of γ-aminobutyric acid and glutamate in patients with major depression
Subtype-specific alterations of γ-aminobutyric acid and glutamate in patients with major depression
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DOI：
10.1001/archpsyc.61.7.705
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发表时间：
2004-07-01
影响因子：
--
通讯作者：
Mason, GF
中科院分区：
文献类型：
--
作者：
Sanacora, G;Gueorguieva, R;Mason, GF
背景：利用质子磁共振波谱法测量皮质γ -氨基丁酸（GABA）和谷氨酸浓度是可能的。一份使用该技术的初步报告表明，与健康对照受试者相比，重度抑郁症（MDD）患者枕叶皮质GABA浓度降低。目的：在更大的MDD患者样本中重复GABA的发现，检查这些受试者中GABA减少的临床相关性，并检查其他关键代谢物水平。设计：联想研究。设置：学术临床研究项目。参与者：对38名健康对照者和33名抑郁症患者进行了GABA测定。干预措施：使用质子磁共振波谱法测量枕皮质代谢物水平。主要观察指标：比较两组枕叶皮质GABA、谷氨酸、n -乙酰天冬氨酸、天冬氨酸、肌酸和含胆碱化合物的水平，以及几种组织组成指标。结果：抑郁受试者枕皮质GABA浓度显著低于健康对照组（P = 0.01）。此外，与健康对照组相比，抑郁症患者的平均谷氨酸水平显著升高（P < 0.001）。体素中实体组织百分比（P = 0.009）和白质百分比（P = 0.04）也显著降低。对包括原始研究对象在内的联合数据库的检查表明，GABA和谷氨酸浓度在MDD亚型中存在差异。结论：本研究重复了重度抑郁症患者枕叶皮层GABA浓度下降的结果。研究还表明，抑郁受试者皮层中兴奋抑制性神经递质水平的比例发生了变化，这可能与大脑功能的改变有关。最后，综合数据集表明，磁共振波谱GABA测量可能作为MDD亚型的生物学标记物。
Background: Measurement of cortical gamma-aminobutyric acid (GABA) and glutamate concentrations is possible using proton magnetic resonance spectroscopy. An initial report, using this technique, suggested that occipital cortex GABA concentrations are reduced in patients with major depressive disorder (MDD) relative to healthy comparison subjects.Objectives: To replicate the GABA findings in a larger sample of MDD patients, to examine the clinical correlates of the GABA reductions in these subjects, and to examine other critical metabolite levels.Design: Study for association.Setting: Academic clinical research program.Participants: The GABA measurements were made on 38 healthy control subjects and 33 depressed subjects.Interventions: Occipital cortex metabolite levels were measured using proton magnetic resonance spectroscopy.Main Outcome Measures: The levels of occipital cortex GABA, glutamate, N-acetylaspartate, aspartate, creatine, and choline-containing compounds, along with several measures of tissue composition, were compared between the 2 groups.Results: Depressed subjects had significantly lower occipital cortex GABA concentrations compared with healthy controls (P = .01). In addition, mean glutamate levels were significantly increased in depressed subjects compared with healthy controls (P < .001). Significant reductions in the percentage of solid tissue (P = .009) and the percentage of white matter (P = .04) in the voxel were also observed. An examination of a combined database including subjects from the original study suggests that GABA and glutamate concentrations differ among MDD subtypes.Conclusions: The study replicates the findings of decreased GABA concentrations in the occipital cortex of subjects with MDD. It also demonstrates that there is a change in the ratio of excitatory-inhibitory neurotransmitter levels in the cortex of depressed subjects that may be related to altered brain function. Last, the combined data set suggests that magnetic resonance spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.