The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study.
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 3T with MRI, multi-voxel 3-dimensional, high, 0.75 cm(3), 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.
NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, New York, New York, USA. vilma.gabbay@nyumc.org
Vilma
V
Gabbay
Leonard
L
Liebes
Yisrael
Y
Katz
Songtao
S
Liu
Sandra
S
Mendoza
James S
JS
Babb
Rachel G
RG
Klein
Oded
O
Gonen
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping; D002794:Choline / Q000378:metabolism; D003863:Depression / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000097:blood; D055815:Young Adult
D015095:3-Hydroxyanthranilic Acid; D001224:Aspartic Acid; D007737:Kynurenine; D014364:Tryptophan; C000179:N-acetylaspartate; D002794:Choline