Kynurenine pathway metabolites and suicidality

Suicide is a major global problem, claiming more than 800,000 lives annually. The neurobiological changes that underlie suicidal ideation and behavior are not fully understood. Suicidal patients have been shown to display elevated levels of inflammation both in the central nervous system and the peripheral blood. A growing body of evidence suggests that inflammation is associated with a dysregulation of the kynurenine pathway in suicidal patients, resulting in an imbalance of neuroactive metabolites. Specifically, an increase in the levels of the NMDA receptor agonist quinolinic acid and a simultaneous decrease in neuroprotective metabolites have been observed in suicidal patients, and may contribute to the development of suicidality via changes in glutamate neurotransmission and neuroinflammation. The cause of the dysregulation of kynurenine metabolites in suicidality is not known, but is likely due to differential activity of the involved enzymes in patients. As knowledge in these areas is rapidly growing, targeting the lcynurenine pathway enzymes may provide novel therapeutic approaches for managing suicidal behavior. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. (C) 2016 The Authors. Published by Elsevier Ltd.