Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan; Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, 187-8551, Japan.
J Psychiatr Res. 2018 Jan;96:23-32. doi: 10.1016/j.jpsychires.2017.09.014. Epub 2017 Sep 19.
Some amino acids act as neurotransmitters themselves, or are precursors of neurotransmitters. Previous studies reported inconsistent results regarding their changes in blood in major depressive disorder (MDD), which prompted us to examine plasma levels of amino acids and related molecules in two independent case-control sample sets. In total, 511 subjects were recruited. Sample set A consisted of 164 patients with MDD (147 currently depressed [dMDD]; 17 in remission, DSM-IV) and 217 healthy controls. Sample set B consisted of 65 patients (51 dMDD; 14 in remission) and 65 controls. Plasma amino acid levels were measured using high-performance liquid chromatography for set A and liquid chromatography/mass spectrometry for set B. We further analyzed the relationships between plasma amino acid levels and clinical variables. In sample set A, plasma asparagine, histidine+1-methylhistidine, methionine, phenylalanine, tryptophan, and tyrosine levels were decreased, while plasma glutamate and phosphoethanolamine were elevated in dMDD compared to controls (all P < 0.0005), even after correcting for multiple testing. Plasma leucine levels were associated with "psychic anxiety." In sample set B, glutamate and methionine levels were also altered in the same direction to that in sample set A (both P < 0.05). In the integrative analysis, plasma glutamate and methionine levels were found to be significantly associated with the diagnosis of MDD with small to medium effect sizes (both P < 1.0E-6). In conclusion, several amino acids and related molecules were altered in patients with MDD. Decreased methionine and increased glutamate levels were found consistently in the two sample sets, suggesting their involvement in MDD. Further investigations are warranted on the possible role of amino acids in the pathophysiology of MDD.
一些氨基酸本身可以作为神经递质，或者是神经递质的前体。之前的研究报告称，在重度抑郁症（MDD）患者的血液中，这些氨基酸的含量存在不一致的变化，这促使我们在两个独立的病例对照样本集中检查了氨基酸和相关分子的血浆水平。共有 511 名受试者被招募。样本集 A 包括 164 名 MDD 患者（147 名当前抑郁 [dMDD]；17 名缓解期，DSM-IV）和 217 名健康对照者。样本集 B 由 65 名患者（51 名 dMDD；14 名缓解期）和 65 名对照者组成。使用高效液相色谱法（set A）和液相色谱/质谱法（set B）测定血浆氨基酸水平。我们进一步分析了血浆氨基酸水平与临床变量之间的关系。在样本集 A 中，与对照组相比，dMDD 患者的血浆天冬酰胺、组氨酸+1-甲基组氨酸、蛋氨酸、苯丙氨酸、色氨酸和酪氨酸水平降低，而谷氨酸和磷酸乙醇胺升高（所有 P 值均 < 0.0005），即使在进行了多次检验校正后也是如此。血浆亮氨酸水平与“精神焦虑”有关。在样本集 B 中，谷氨酸和蛋氨酸水平也以与样本集 A 相同的方向发生变化（均 P 值 < 0.05）。在整合分析中，发现谷氨酸和蛋氨酸的血浆水平与 MDD 的诊断显著相关，具有小到中等的效应大小（均 P 值 < 1.0E-6）。总之，一些氨基酸和相关分子在 MDD 患者中发生了改变。在两个样本集中均发现蛋氨酸水平降低和谷氨酸水平升高，这表明它们可能与 MDD 有关。有必要进一步研究氨基酸在 MDD 病理生理学中的可能作用。
