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Altered tryptophan–kynurenine (KYN) metabolism has been implicated in major depressive disorder (MDD). The  l -[1- 13 C]tryptophan breath test ( 13 C-TBT) is a noninvasive, stable-isotope tracer method in which exhaled  13 CO 2  is attributable to tryptophan catabolism via the KYN pathway. We included 18 patients with MDD (DSM-IV) and 24 age- and sex-matched controls.  13 C-tryptophan (150 mg) was orally administered and the  13 CO 2 / 12 CO 2  ratio in the breath was monitored for 180 min. The cumulative recovery rate during the 180-min test (CRR 0–180 ; %), area under the Δ 13 CO 2 -time curve (AUC; %*min), and the maximal Δ 13 CO 2  (C max ; %) were significantly higher in patients with MDD than in the controls (p = 0.004, p = 0.008, and p = 0.002, respectively). Plasma tryptophan concentrations correlated negatively with C max  in both the patients and controls (p = 0.020 and p = 0.034, respectively). Our results suggest that the  13 C-TBT could be a novel biomarker for detecting a subgroup of MDD with increased tryptophan–KYN metabolism.

13C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder