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Auteur Leonard LIEBES |
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The possible role of the kynurenine pathway in adolescent depression with melancholic features / Vilma GABBAY in Journal of Child Psychology and Psychiatry, 51-8 (August 2010)
[article]
Titre : The possible role of the kynurenine pathway in adolescent depression with melancholic features Type de document : Texte imprimé et/ou numérique Auteurs : Vilma GABBAY, Auteur ; Rachel G. KLEIN, Auteur ; Yisrael KATZ, Auteur ; Sandra MENDOZA, Auteur ; Leah E. GUTTMAN, Auteur ; Carmen M. ALONSO, Auteur ; James S. BABB, Auteur ; Glenn S. HIRSCH, Auteur ; Leonard LIEBES, Auteur Année de publication : 2010 Article en page(s) : p.935-943 Langues : Anglais (eng) Mots-clés : Adolescent-depression indoleamine dioxygenase IDO kynurenine-(KYN) tryptophan(TRP) melancholic MDD subtypes Index. décimale : PER Périodiques Résumé : Background: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites.
Methods: Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale-Revised (CDRS-R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons.
Results: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R.
Conclusions: Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome.En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02245.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=108
in Journal of Child Psychology and Psychiatry > 51-8 (August 2010) . - p.935-943[article] The possible role of the kynurenine pathway in adolescent depression with melancholic features [Texte imprimé et/ou numérique] / Vilma GABBAY, Auteur ; Rachel G. KLEIN, Auteur ; Yisrael KATZ, Auteur ; Sandra MENDOZA, Auteur ; Leah E. GUTTMAN, Auteur ; Carmen M. ALONSO, Auteur ; James S. BABB, Auteur ; Glenn S. HIRSCH, Auteur ; Leonard LIEBES, Auteur . - 2010 . - p.935-943.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 51-8 (August 2010) . - p.935-943
Mots-clés : Adolescent-depression indoleamine dioxygenase IDO kynurenine-(KYN) tryptophan(TRP) melancholic MDD subtypes Index. décimale : PER Périodiques Résumé : Background: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites.
Methods: Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale-Revised (CDRS-R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons.
Results: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R.
Conclusions: Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome.En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02245.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=108