Unlocking the potential of the 3-hydroxykynurenine/kynurenic acid ratio: a promising biomarker in adolescent major depressive disorder.

Metabolites disruptions in tryptophan (TRP) and kynurenine pathway (KP) are believed to disturb neurotransmitter homeostasis and contribute to depressive symptoms. This study aims to investigate serum levels of KP metabolites in adolescent major depressive disorder (AMDD), and examine their relationship with depression severities. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze serum levels of TRP, kynurenic acid (KYNA), kynurenine (KYN), and 3-hydroxy-kynurenine (3-HK) in 143 AMDD participants and 98 healthy controls (HC). Clinical data, including Children's Depression Inventory (CDI) scores, were collected and analyzed using statistical methods, such as ANOVA, logistic regression, Receiver operating characteristic curve analysis and a significance level of p < 0.05 was used for all analyses. AMDD showed significantly decreased serum levels of KYNA (-25.5%), KYN (-14.2%), TRP (-11.0%) and the KYNA/KYN ratio (-11.9%) compared to HC (p < 0.01). Conversely, significant increases were observed in 3-HK levels (+50.4%), the 3-HK/KYNA ratio (+104.3%) and the 3-HK/KYN ratio (+93.0%) (p < 0.01). Logistic regression analysis identified increased level of 3-HK as a contributing factor to AMDD, while increased level of KYNA acted as a protective factor against AMDD. The 3-HK/KYNA ratio demonstrated an area under the curve (AUC) of 0.952. This study didn't explore AMDD's inflammatory status and its metabolites relationship explicitly. These findings indicate that metabolites of TRP and KP may play a crucial role in the pathogenesis of AMDD, emphasizing the potential of the 3-HK/KYNA ratio as a laboratory biomarker for early detection and diagnosis of AMDD.