Connecting inflammation with glutamate agonism in suicidality.
Connecting inflammation with glutamate agonism in suicidality.
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DOI：
10.1038/npp.2012.248
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发表时间：
2013-04
期刊：
影响因子：
--
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中科院分区：
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NMDA受体拮抗剂氯胺酮已被证明有效地减少自杀症状，尽管解释这种作用的机制尚未在精神病患者中详细说明。最近的证据表明，自杀受害者的大脑中存在轻度炎症。炎症导致喹啉酸（QUIN）和犬尿烯酸（KYNA）的产生，它们分别是谷氨酸能N-甲基-D-天冬氨酸（NMDA）受体的激动剂和拮抗剂。我们在这里测量了64名无药物自杀未遂者和36名对照者的脑脊液（CSF）中的QUIN和KYNA，使用气相色谱-质谱法和高效液相色谱法。我们使用自杀意图量表和蒙哥马利-艾斯伯格抑郁量表（MADRS）对患者进行临床评估。我们发现自杀未遂者的脑脊液中QUIN而非KYNA显著升高（P<0.001）。正如预测的那样，QUIN的增加与CSF白细胞介素-6水平升高相关。此外，QUIN水平与自杀意图量表总分相关。在自杀未遂后6个月内进行随访腰椎穿刺的患者中，QUIN显著降低。总之，我们在这里提出的临床证据表明，增加QUIN在CSF中的自杀未遂。增加的QUIN/KYNA商数支持总体NMDA受体刺激。QUIN和自杀意图量表之间的相关性表明，多巴胺能神经传递的变化可能与自杀有关。我们的发现对自杀患者的检测和特异性治疗具有重要意义，并可能解释氯胺酮的治疗作用。
The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery–Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (P<0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine.
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DOI：
10.4088/jcp.09m05327blu
发表时间：
2010-12
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
DiazGranados N;Ibrahim LA;Brutsche NE;Ameli R;Henter ID;Luckenbaugh DA;Machado-Vieira R;Zarate CA Jr
通讯作者：
Zarate CA Jr
影响因子：
11.3
作者：
Claes, Stephan;Myint, Aye-Mu;Rothermundt, Matthias
通讯作者：
Rothermundt, Matthias
影响因子：
3.1
作者：
Da Cruz, D.;Pearson, A.;Kapur, N.
通讯作者：
Kapur, N.
影响因子：
15.1
作者：
Janelidze, Shorena;Mattei, Daniele;Brundin, Lena
通讯作者：
Brundin, Lena
影响因子：
14.5
作者：
HEYES, MP;SAITO, K;TOURTELLOTTE, WW
通讯作者：
TOURTELLOTTE, WW