The Possible Role of the Kynurenine Pathway in Adolescent Depression with Melancholic Features

Autor/inn/en	Gabbay, Vilma; Klein, Rachel G.; Katz, Yisrael; Mendoza, Sandra; Guttman, Leah E.; Alonso, Carmen M.; Babb, James S.; Hirsch, Glenn S.; Liebes, Leonard
Titel	The Possible Role of the Kynurenine Pathway in Adolescent Depression with Melancholic Features
Quelle	In: Journal of Child Psychology and Psychiatry, 51 (2010) 8, S.935-943 (9 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0021-9630
DOI	10.1111/j.1469-7610.2010.02245.x
Schlagwörter	Rating Scales; Adolescents; Statistical Analysis; Depression (Psychology); Correlation; Biochemistry; Metabolism; Brain Hemisphere Functions; Control Groups; Severity (of Disability); Measures (Individuals); Scores; Drug Therapy; Patients + Suchen Sie Ihr Suchwort? Rating-Skala; Adolescent; Adolescence; Adoleszenz; Jugend; Jugendalter; Jugendlicher; Statistische Analyse; Korrelation; Biochemie; Stoffwechsel; Schweregrad; Messdaten; Patient
Abstract	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 greater than or equal to 6 weeks and Children's Depression Rating Scale-Revised (CDRS-R) scores were greater than or equal to 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 = 0.001 and .006, respectively) and to healthy controls (p = 0.008 and 0.022, 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. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10