Kynurenine pathway profiles as markers of ketamine response in treatment-resistant depression.
Brain, behavior, and immunity July 5, 2026 Bruno Pedraz-Petrozzi, Marta Marszalek-Grabska, Emilia Fornal et al.
In adults with treatment-resistant depression receiving six intravenous ketamine infusions over three weeks, higher baseline levels of the neuroprotective metabolite kynurenic acid (KYNA) in the kynurenine pathway were associated with greater symptom improvement by day 18. KYNA remained stable over time and did not track with symptom changes, suggesting it acts as a trait-like marker rather than a state-dependent one. Early shifts toward the neurotoxic branch of the pathway (kynurenine and 3-hydroxykynurenine) were linked to reductions in hopelessness and suicidality scores after the first infusion. These exploratory findings indicate that a kynurenine pathway profile biased toward neuroprotective metabolites may inform future biomarker studies of ketamine response, but require validation in larger samples.