Abnormalities in kynurenine pathway metabolism in treatment-resistant depression and suicidality: a systematic review

Research output: Contribution to journalReview article


Treatment resistant depression (TRD) and suicidal behavior are among the most important public health problems and are commonly associated with significant disability and psychosocial impairment. Although there have been recent advances in identifying neurobiological correlates of these complex conditions, their pathophysiology still remains unclear. Although the recent advances concerning the neurobiological determinants underlying these complex conditions, their pathophysiology still remains unclear. Compared to non-suicidal subjects, higher mean concentrations of inflammatory mediators have been found in both the periphery and brain of individuals at risk for suicide. Several lines of evidence suggest that neuroinflammation is accompanied by a dysregulation of the kynurenine pathway (KP) in both TRD and suicidal individuals, resulting in an imbalance of neuroactive metabolites. In particular, neuroinflammation may trigger an increased production of the N-Methyl-D-aspartate (NMDA) receptor agonist quinolinic acid and a concomitant reduction of neuroprotective metabolites, potentially causing downstream effects in glutamatergic systems resulting in depressive symptoms and suicidal behavior. This systematic review of the current literature is mainly aimed at summarizing the most important evidence pertaining to KP metabolism abnormalities in TRD and suicidal behavior. Targeting the KP enzymes may provide innovative approaches in the management of both TRD and suicidality.


  • Gianluca Serafini
  • Giulia Adavastro
  • Giovanna Canepa
  • Laura Capobianco
  • Claudia Conigliaro
  • Federica Pittaluga
  • Martino Belvederi Murri
  • Alessandro Valchera
  • Domenico De Berardis
  • Maurizio Pompili
  • Daniel Lindqvist
  • Lena Brundin
  • Mario Amore
External organisations
  • University of Genoa
  • Sapienza University of Rome
  • Van Andel Research Institute
  • Villa San Giuseppe Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Psychiatry


  • Kynurenine pathway, quinolinic acid, tryptophan, treatment-resistant depression, suicidal behavior
Original languageEnglish
Pages (from-to)440 - 453
JournalCNS and Neurological Disorders - Drug Targets
Issue number4
Early online date2017 Apr 13
Publication statusPublished - 2017
Publication categoryResearch