Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder.
Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder.
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DOI：
10.1038/s41398-021-01541-1
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发表时间：
2021-08-05
影响因子：
6.8
通讯作者：
John Mann J
中科院分区：
文献类型：
--
作者：
Kantrowitz JT;Dong Z;Milak MS;Rashid R;Kegeles LS;Javitt DC;Lieberman JA;John Mann J
谷氨酸（Glu）和γ-氨基丁酸（GABA）与重度抑郁症（MDD）的病理生理学有关。GABA水平或GABA能中间神经元数量在MDD中通常较低，可能抑制Glu释放。目前尚不清楚是否Glu释放或营业额增加抑郁症。相反，对MDD患者的前额质子磁共振波谱（1H MRS）研究的荟萃分析发现，药物治疗的MDD患者Glx（谷氨酸和谷氨酰胺的组合）较低。我们假设Glx或Glu升高可能是更严重的未经治疗的MDD的标志物。我们研究腹内侧前额叶皮层/前扣带皮层（vmPFC/ACC）Glx和谷氨酸水平使用1H MRS在34个药物治疗，症状，慢性疾病MDD患者和32名健康志愿者，和GABA水平的子样本。与健康志愿者相比，在MDD中观察到Glx和Glu升高，在MDD男性中观察到最高水平。MDD患者vmPFC/ACC GABA水平较低。较高的Glx水平与更严重的抑郁症和较低的GABA相关。MDD的严重程度和诊断均与vmPFC/ACC中较高的Glx相关。这些患者中的一个亚组中的低GABA与我们假设的低GABA导致MDD中谷氨酸去抑制的模型一致。这一发现和模型与我们先前报道的发现一致，即NMDAR拮抗剂抗抑郁作用与vmPFC/ACC Glx或Glu水平的降低成比例。
Glutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers are generally low in MDD, potentially disinhibiting Glu release. It is unclear whether Glu release or turnover is increased in depression. Conversely, a meta-analysis of prefrontal proton magnetic resonance spectroscopy (1H MRS) studies in MDD finds low Glx (combination of glutamate and glutamine) in medicated MDD. We hypothesize that elevated Glx or Glu may be a marker of more severe, untreated MDD. We examined ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC) Glx and glutamate levels using 1H MRS in 34 medication-free, symptomatic, chronically ill MDD patients and 32 healthy volunteers, and GABA levels in a subsample. Elevated Glx and Glu were observed in MDD compared with healthy volunteers, with the highest levels seen in males with MDD. vmPFC/ACC GABA was low in MDD. Higher Glx levels correlated with more severe depression and lower GABA. MDD severity and diagnosis were both linked to higher Glx in vmPFC/ACC. Low GABA in a subset of these patients is consistent with our hypothesized model of low GABA leading to glutamate disinhibition in MDD. This finding and model are consistent with our previously reported findings that the NMDAR-antagonist antidepressant effect is proportional to the reduction of vmPFC/ACC Glx or Glu levels.
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