title: Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder.
abstract: BACKGROUND
  Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with major depressive disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers.
  
  
  METHODS
  Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n=31) and patients with MDD with (n=14) and without (n=16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels.
  
  
  RESULTS
  KYN levels differed across groups (F=4.03, df=(2,58), and p=0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t=2.105, df=58, and p=0.040), who did not differ from healthy volunteers (t=0.418, df=58, and p=0.677). In post hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters.
  
  
  CONCLUSIONS
  These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior.
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, United States. es2316@columbia.edu
authors: M Elizabeth
authors: ME
authors: Sublette
authors: Hanga C
authors: HC
authors: Galfalvy
authors: Dietmar
authors: D
authors: Fuchs
authors: Manana
authors: M
authors: Lapidus
authors: Michael F
authors: MF
authors: Grunebaum
authors: Maria A
authors: MA
authors: Oquendo
authors: J John
authors: JJ
authors: Mann
authors: Teodor T
authors: TT
authors: Postolache
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