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CNS Neurol Disord Drug Targets. 2017;16(4):440-453. doi: 10.2174/1871527316666170413110605.

Abnormalities in Kynurenine Pathway Metabolism in Treatment-Resistant Depression and Suicidality: A Systematic Review.

Author information

1
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, IRCCS San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy.
2
Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.
3
Villa San Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy; Polyedra Research Group, Teramo, Italy.
4
NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", Asl 4 Teramo, Italy.
5
Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Italy.
6
Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Psychiatry, Lund. Sweden.
7
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, United States.

Abstract

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; metabolism; quinolinic acid; suicidal behavior; treatment-resistant depression; tryptophan

[Indexed for MEDLINE]

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