The kynurenine pathway in adolescent depression: Preliminary findings from a proton MR spectroscopy study

Vilma Gabbay, Leonard Liebes, Yisrael Katz, Songtao Liu, Sandra Mendoza, James S. Babb, Rachel G. Klein, Oded Gonen

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background: Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins. The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho; and, ii) the anticipated correlations would be more pronounced in the melancholic subtype group. Methods: Fourteen adolescents with MDD (seven with melancholic features) and six healthy controls were enrolled. Minimums of 6 weeks MDD duration and a severity score of 40 on the Children's Depression Rating Scale-Revised were required. All were scanned at 3 T with MRI, multi-voxel 3-dimensional, high, 0.75 cm3, spatial resolution proton magnetic resonance spectroscopic imaging. Striatal tCho concentrations were assessed using phantom replacement. Spearman correlation coefficients were Bonferroni-corrected. Results: Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate (r = 0.93, p = 0.03) and the left putamen (r = 0.96, p = .006), respectively. Conclusions: These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD. Larger studies should follow.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume34
Issue number1
DOIs
StatePublished - Jan 20 2010
Externally publishedYes

Keywords

  • Adolescent MDD
  • Choline
  • Kynurenine pathway
  • Melancholic
  • MR Spectroscopy
  • Striatum

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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