TY - JOUR
T1 - The kynurenine pathway in adolescent depression
T2 - Preliminary findings from a proton MR spectroscopy study
AU - Gabbay, Vilma
AU - Liebes, Leonard
AU - Katz, Yisrael
AU - Liu, Songtao
AU - Mendoza, Sandra
AU - Babb, James S.
AU - Klein, Rachel G.
AU - Gonen, Oded
PY - 2010/1/20
Y1 - 2010/1/20
N2 - 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.
AB - 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.
KW - Adolescent MDD
KW - Choline
KW - Kynurenine pathway
KW - MR Spectroscopy
KW - Melancholic
KW - Striatum
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U2 - 10.1016/j.pnpbp.2009.09.015
DO - 10.1016/j.pnpbp.2009.09.015
M3 - Article
C2 - 19778568
AN - SCOPUS:73649114218
SN - 0278-5846
VL - 34
SP - 37
EP - 44
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
IS - 1
ER -