Psychiatric University Hospital, University of Bern, Bern, Switzerland.
Unit of Psychiatry Research, University of Fribourg, Villars-sur-Glâne, Switzerland.
JAMA Psychiatry. 2022 Dec 1;79(12):1209-1216. doi: 10.1001/jamapsychiatry.2022.3384.
Major depressive disorder (MDD) is one of the most prevalent illnesses worldwide. Perturbations of the major inhibitory and excitatory neurotransmitters, γ-aminobutyric acid (GABA) and glutamate (Glu), respectively, as well as Glx (Glu or glutamine [Gln]) have been extensively reported in a multitude of brain areas of individuals with depression, but few studies have examined changes in Gln, the metabolic counterpart of synaptic Glu.
To investigate changes in GABA, Glx, Glu, and Gln levels in a voxel in the left dorsolateral prefrontal cortex of participants with no, past, and current MDD using proton magnetic resonance spectroscopy (1H-MRS).
DESIGN, SETTING, AND PARTICIPANTS: This community-based study used a cross-sectional design using 3-T 1H-MRS in participants not taking MDD medication recruited from the community. The sample consisted of 251 healthy controls, 98 participants with a history of past MDD, and 47 participants who met the diagnostic criteria for current MDD. Diagnostic groups were comparable regarding age, education, income, and diet. Data were collected from March 2014 to October 2021, and data were analyzed from October 2021 to June 2022.
GABA, Glx, Glu, and Gln concentrations in the left dorsolateral prefrontal cortex.
Of 396 included participants, 258 (65.2%) were female, and the mean (SD) age was 25.0 (4.7) years. Compared with healthy controls, those with past MDD and current MDD had lower GABA concentrations (mean [SEM] concentration: healthy controls, 2.70 [0.03] mmol/L; past MDD, 2.49 [0.05] mmol/L; current MDD, 2.54 [0.07] mmol/L; 92 with past MDD vs 236 healthy controls: r = 0.18; P = .002; 44 with current MDD vs 236 healthy controls: r = 0.13; P = .04). Compared with healthy controls, those with past MDD also had lower Glu concentrations (mean [SEM] concentration: healthy controls, 7.52 [0.06] mmol/L; past MDD, 7.23 [0.11] mmol/L; 93 with past MDD vs 234 healthy controls: r = 0.16; P = .01) and higher Gln concentrations (mean [SEM] concentration: healthy controls, 1.63 [0.04] mmol/L; past MDD, 1.84 [0.07] mmol/L; 66 with past MDD 153 healthy controls: r = 0.17; P = .04).
In a large, mostly medication-free community sample, reduced prefrontal GABA concentrations were associated with past MDD, consistent with histopathologic studies reporting reduced glial cell and GABA cell density in the prefrontal cortex in individuals with depression. Patients with MDD also demonstrated increased Gln levels, indicative of increased synaptic Glu release, adding to previous evidence for the Glu hypothesis of MDD.
重度抑郁症（MDD）是全球最常见的疾病之一。分别在许多抑郁症患者的大脑区域中广泛报道了主要抑制性和兴奋性神经递质γ-氨基丁酸（GABA）和谷氨酸（Glu）以及 Glx（Glu 或谷氨酰胺[Gln]）的波动，但很少有研究检查过 Gln 的变化，Gln 是突触 Glu 的代谢对应物。
使用质子磁共振波谱（1H-MRS）在无、过去和当前 MDD 参与者的左侧背外侧前额叶皮质的体素中研究 GABA、Glx、Glu 和 Gln 水平的变化。
设计、地点和参与者：这项基于社区的研究使用了横断面设计，在社区中招募未服用 MDD 药物的参与者，使用 3-T 1H-MRS。样本包括 251 名健康对照者、98 名有过去 MDD 病史的参与者和 47 名符合当前 MDD 诊断标准的参与者。诊断组在年龄、教育、收入和饮食方面具有可比性。数据于 2014 年 3 月至 2021 年 10 月收集，数据于 2021 年 10 月至 2022 年 6 月进行分析。
左侧背外侧前额叶皮质的 GABA、Glx、Glu 和 Gln 浓度。
在纳入的 396 名参与者中，258 名（65.2%）为女性，平均（SD）年龄为 25.0（4.7）岁。与健康对照组相比，有过去 MDD 和当前 MDD 的参与者的 GABA 浓度较低（平均[SEM]浓度：健康对照组，2.70[0.03]mmol/L；过去 MDD，2.49[0.05]mmol/L；当前 MDD，2.54[0.07]mmol/L；92 名有过去 MDD 与 236 名健康对照组：r=0.18；P=0.002；44 名有当前 MDD 与 236 名健康对照组：r=0.13；P=0.04）。与健康对照组相比，有过去 MDD 的参与者的 Glu 浓度也较低（平均[SEM]浓度：健康对照组，7.52[0.06]mmol/L；过去 MDD，7.23[0.11]mmol/L；93 名有过去 MDD 与 234 名健康对照组：r=0.16；P=0.01），Gln 浓度较高（平均[SEM]浓度：健康对照组，1.63[0.04]mmol/L；过去 MDD，1.84[0.07]mmol/L；66 名有过去 MDD 与 153 名健康对照组：r=0.17；P=0.04）。
在一个大型的、主要无药物的社区样本中，前额叶 GABA 浓度降低与过去的 MDD 相关，与报告抑郁症患者前额皮质中神经胶质细胞和 GABA 细胞密度降低的组织病理学研究一致。MDD 患者还表现出 Gln 水平升高，表明突触 Glu 释放增加，这增加了 MDD 的 Glu 假说的先前证据。
