RT Journal Article SR Electronic T1 Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals JF Journal of Psychiatry and Neuroscience JO J Psychiatry Neurosci FD Canadian Medical Association SP 386 OP 394 DO 10.1503/jpn.150226 VO 41 IS 6 A1 Sarah M. Clark A1 Ana Pocivavsek A1 James D. Nicholson A1 Francesca M. Notarangelo A1 Patricia Langenberg A1 Robert P. McMahon A1 Joel E. Kleinman A1 Thomas M. Hyde A1 John Stiller A1 Teodor T. Postolache A1 Robert Schwarcz A1 Leonardo H. Tonelli YR 2016 UL http://jpn.ca/content/41/6/386.abstract AB Background: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology.Methods: We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide.Results: We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls.Limitations: Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons.Conclusion: Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.