Gulhane Training and Research Hospital, Department of Psychiatry, Ankara, Turkey.
Noro Saglik Brain Trainings Research Application Center, Istanbul, Turkey.
Schizophr Res. 2019 Apr;206:58-66. doi: 10.1016/j.schres.2018.12.015. Epub 2018 Dec 23.
Agmatine is an endogenous NMDA (N-methyl-d-aspartate) antagonist which is synthesized from l-Arginine and described as a novel neurotransmitter. Agmatine is considered to play an important role for the development of schizophrenia. The aim of the present study is to explore the role of agmatine and l-arginine metabolism in medication-naive first-episode psychosis (FEP). We conducted a case control study in medication-naive patients with FEP (n = 40). The healthy volunteers with no family history of schizophrenia (n = 35) matched for age, gender and education level were selected as a control group. The patients were recruited to the study and followed up for 10 weeks. The plasma l-arginine, l-citrulline, l-ornithine and agmatine levels were measured using modified liquid chromatography/mass spectrometry. The plasma levels of l-arginine, l-citrulline and agmatine (p < 0.0001), but not l-ornithine and agmatinase (p > 0.05), were significantly increased during baseline analysis. After 10 weeks of treatment, plasma l-arginine and l-citrulline levels were still significantly increased (p < 0.05) while l-ornithine and agmatinase levels remained unchanged (p > 0.05). Conversely, plasma agmatine levels were significantly decreased after the treatment (p < 0.0001). Positive and negative predictive values of agmatine used for evaluating the diagnostic accuracy were 95.1% and 97.1%, respectively (p < 000.1). This is the first study of arginine metabolism and agmatine in medication-naive first-episode patients and provides evidence of increased levels of an endogenous NMDA antagonist which decreases following antipsychotic treatment.
胍丁胺是一种内源性 NMDA（N-甲基-D-天冬氨酸）拮抗剂，由 l-精氨酸合成，并被描述为一种新型神经递质。胍丁胺被认为在精神分裂症的发展中发挥重要作用。本研究旨在探讨胍丁胺和 l-精氨酸代谢在未经药物治疗的首发精神病（FEP）患者中的作用。我们进行了一项未经药物治疗的首发精神病患者的病例对照研究（n=40）。选择无精神分裂症家族史的健康志愿者（n=35），按年龄、性别和教育程度匹配为对照组。招募患者入组并进行 10 周随访。采用改良液相色谱/质谱法测定血浆 l-精氨酸、l-瓜氨酸、l-鸟氨酸和胍丁胺水平。在基线分析中，血浆 l-精氨酸、l-瓜氨酸和胍丁胺水平（p<0.0001）显著升高，但 l-鸟氨酸和精氨酸酶水平（p>0.05）没有变化。治疗 10 周后，血浆 l-精氨酸和 l-瓜氨酸水平仍显著升高（p<0.05），而 l-鸟氨酸和精氨酸酶水平仍无变化（p>0.05）。相反，治疗后血浆胍丁胺水平显著降低（p<0.0001）。胍丁胺用于评估诊断准确性的阳性和阴性预测值分别为 95.1%和 97.1%（p<0.000.1）。这是首次在未经药物治疗的首发精神病患者中研究精氨酸代谢和胍丁胺，为内源性 NMDA 拮抗剂水平升高提供了证据，这种拮抗剂在抗精神病治疗后会降低。
