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

Serafini, Gianluca; Adavastro, Giulia; Canepa, Giovanna; Capobianco, Laura; Conigliaro, Claudia; Pittaluga, Federica; Belvederi Murri, Martino; Valchera, Alessandro; De Berardis, Domenico and Pompili, Maurizio, et al. (2017) In CNS and Neurological Disorders - Drug Targets 16(4). p.440-453
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 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... (More)

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.

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keywords
Kynurenine pathway, quinolinic acid, tryptophan, treatment-resistant depression, suicidal behavior
in
CNS and Neurological Disorders - Drug Targets
volume
16
issue
4
pages
440 - 453
publisher
Bentham Science Publishers
external identifiers
  • scopus:85027269075
  • wos:000405318900008
ISSN
1871-5273
DOI
10.2174/1871527316666170413110605
language
English
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yes
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22a9d1ac-a16c-4776-b17d-62d14812fab8
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2017-04-30 15:04:34
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2017-09-18 13:33:32
@article{22a9d1ac-a16c-4776-b17d-62d14812fab8,
  abstract     = {<p>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.</p>},
  author       = {Serafini, Gianluca and Adavastro, Giulia and Canepa, Giovanna and Capobianco, Laura and Conigliaro, Claudia and Pittaluga, Federica and Belvederi Murri, Martino and Valchera, Alessandro and De Berardis, Domenico and Pompili, Maurizio and Lindqvist, Daniel and Brundin, Lena and Amore, Mario},
  issn         = {1871-5273},
  keyword      = {Kynurenine pathway,quinolinic acid, tryptophan,treatment-resistant depression,suicidal behavior },
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {440--453},
  publisher    = {Bentham Science Publishers},
  series       = {CNS and Neurological Disorders - Drug Targets},
  title        = {Abnormalities in kynurenine pathway metabolism in treatment-resistant depression and suicidality : a systematic review},
  url          = {http://dx.doi.org/10.2174/1871527316666170413110605},
  volume       = {16},
  year         = {2017},
}