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 the neurobiological correlates of
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 to summarize 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.
Keywords: Kynurenine pathway, quinolinic acid, suicidal behavior, treatment-resistant depression, tryptophan, metabolism.
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