The potential role of kynurenine pathway and inflammation in pediatric obsessive-compulsive disorder with and without major depressive disorder comorbidity

Ünal K., Taş Torun Y., Kurt Z. K.

Journal of Neural Transmission, cilt.1, sa.1, ss.1, 2026 (Hakemli Dergi)

Özet

The etiopathogenesis of pediatric obsessive-compulsive disorder (OCD) still remains unclear. Recent literature highlights the involvement of the kynurenine pathway (KP) in psychiatric disorders, particularly major depressive disorder (MDD). However, the potential role of KP in pediatric OCD has yet to be explored. This study aimed to compare serum levels of KP metabolites, including tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN), and inflammatory markers such as CRP, TNF-α, IL-6, IFN-γ, and TWEAK, in children and adolescents diagnosed with OCD with and without comorbid MDD, and healthy controls, after adjustments for potential confounding factors. Ratios reflecting KP enzyme activities (KYN/TRP, KYNA/KYN, QUIN/KYN) and the neurotoxic index (QUIN/KYNA) were also compared, alongside correlations between inflammatory markers and KP parameters. Serum levels of KP metabolites, TNF-α, IFN-γ, and TWEAK were determined using enzyme-linked immunosorbent assay, IL-6 via electrochemiluminescence immunoassay, and CRP via nephelometric method. A total of 107 drug-naïve participants aged 8-18 years were enrolled: 37 with OCD alone, 32 with OCD+MDD, and 38 healthy controls. Compared to the control group, KYN and KYNA levels, and KYN/TRP ratios were lower in the OCD group, while QUIN/KYNA ratios and TWEAK levels were higher. In the patient groups, IFN-γ and TWEAK were positively correlated with TRP, KYNA, QUIN, KYNA/KYN, and QUIN/KYN, but negatively correlated with KYN/TRP. These findings suggest, within a hypothesis-generating framework, that KP alterations related to immune dysregulation may play a role in childhood OCD pathogenesis, especially in noncomorbid forms or early stages