Bryleva Elena Y, Brundin Lena
Laboratory of Behavioral Medicine, Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Ave., Grand Rapids, MI, 49503, USA.
Curr Top Behav Neurosci. 2017;31:269-284. doi: 10.1007/7854_2016_5.
A recent report by the World Health Organization declared suicide to be a major global problem. With more than 800,000 lives lost each year, suicide is calculated to be the 14th leading cause of death around the world. While the biological mechanisms causing suicidal ideation and behavior are not fully understood, increased levels of inflammation, arising from various sources, have been detected in the central nervous system and the peripheral blood of suicidal patients and suicide completers. Inflammation induces the kynurenine pathway of tryptophan metabolism, which generates a range of metabolites with potent effects on neurotransmitter systems as well as on inflammation. Recent evidence indicates that a dysregulation of the enzymes in the kynurenine pathway may be present in suicidal patients, with a resulting imbalance of metabolites that modulate glutamate neurotransmission and neuroinflammation. As the body of research in these areas grows, targeting the kynurenine pathway enzymes and metabolites may provide novel therapeutic opportunities for detection, treatment, and ultimately prevention of suicidal behavior.
世界卫生组织最近的一份报告宣称自杀是一个重大的全球问题。每年有超过80万人死于自杀,据统计,自杀是全球第14大死因。虽然导致自杀意念和行为的生物学机制尚未完全明了,但在自杀患者和自杀身亡者的中枢神经系统和外周血中,已检测到来自各种来源的炎症水平升高。炎症会诱导色氨酸代谢的犬尿氨酸途径,该途径会产生一系列对神经递质系统以及炎症有强效作用的代谢产物。最近的证据表明,自杀患者可能存在犬尿氨酸途径中酶的失调,从而导致调节谷氨酸神经传递和神经炎症的代谢产物失衡。随着这些领域研究的不断增加,针对犬尿氨酸途径的酶和代谢产物可能为检测、治疗以及最终预防自杀行为提供新的治疗机会。