Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Transl Psychiatry. 2017 Aug 22;7(8):e1216. doi: 10.1038/tp.2017.187.
Abnormally low γ-aminobutyric acid (GABA) levels have been consistently reported in adults with major depressive disorder (MDD). Our group extended this finding to adolescents, and documented that GABA deficits were associated with anhedonia. Here we aimed to confirm our prior finding of decreased brain GABA in youth with depression and explore its associations with clinical variables. Forty-four psychotropic medication-free youth with MDD and 36 healthy control (HC) participants (12-21 years) were studied. Participants represent a combined sample of 39 newly recruited youth (MDD=24) and 41 youth from our previously reported study (MDD=20). GABA levels and the combined resonances of glutamate and glutamine (Glx) were measured in vivo in the anterior cingulate cortex using proton magnetic resonance spectroscopy. Youth with depression exhibited significantly lower GABA levels than HC in both the newly reported (P=0.003) and the combined (P=0.003) samples. When depressed participants were classified based on the presence of anhedonia, only the anhedonic MDD subgroup showed reduced GABA levels compared to HC (P=0.002). While there were no associations between any clinical measures and GABA or Glx levels in the new sample, GABA was negatively correlated with only anhedonia severity in the combined MDD group. Furthermore, in the combined sample, hierarchical regression models showed that anhedonia, but not depression severity, anxiety or suicidality, contributed significant variance in GABA levels. This report solidifies the evidence for a GABA deficit early in the course of MDD, which correlates specifically with anhedonia in the disorder.
异常低的γ-氨基丁酸（GABA）水平在患有重度抑郁症（MDD）的成年人中一直有报道。我们的研究小组将这一发现扩展到青少年身上，并记录到 GABA 缺陷与快感缺失有关。在这里，我们旨在确认我们之前在抑郁症青少年中发现的大脑 GABA 减少的发现，并探讨其与临床变量的关系。44 名未服用精神药物的 MDD 青少年和 36 名健康对照组（HC）参与者（12-21 岁）参与了研究。参与者代表了 39 名新招募的青少年（MDD=24）和 41 名来自我们之前报道的研究的青少年（MDD=20）的综合样本。使用质子磁共振波谱法在大脑前扣带皮层测量谷氨酸和谷氨酰胺（Glx）的 GABA 水平和合并共振。与 HC 相比，新报告的（P=0.003）和合并的（P=0.003）样本中，抑郁青少年的 GABA 水平明显降低。当根据快感缺失将抑郁参与者进行分类时，只有快感缺失的 MDD 亚组与 HC 相比显示出 GABA 水平降低（P=0.002）。虽然在新样本中，任何临床指标与 GABA 或 Glx 水平之间都没有关联，但在合并的 MDD 组中，GABA 仅与快感缺失严重程度呈负相关。此外，在合并样本中，分层回归模型显示，快感缺失，但不是抑郁严重程度、焦虑或自杀意念，对 GABA 水平的变异有显著贡献。本报告证实了 MDD 早期存在 GABA 缺陷的证据，该缺陷与该疾病中的快感缺失特异性相关。
