title: (13)C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder.
abstract: 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)CO2 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)CO2/(12)CO2 ratio in the breath was monitored for 180 min. The cumulative recovery rate during the 180-min test (CRR0-180; %), area under the Δ(13)CO2-time curve (AUC; %*min), and the maximal Δ(13)CO2 (Cmax; %) 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 Cmax 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.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Teraishi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Daimei
authors.initials: D
authors.lastname: Sasayama
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuo
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa, 245-0066, Japan.|Tri-X Biomedical, Inc., 4-12-5-406, Minamiyawata, Ichikawa, Chiba, 272-0023, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kajiwara
authors.affiliation: National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8551, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001944:Breath Tests / Q000379:methods*; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D045853:Exhalation; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D012044:Regression Analysis; D014364:Tryptophan / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D000928:Antidepressive Agents; D002247:Carbon Isotopes; D002245:Carbon Dioxide; D007737:Kynurenine; D014364:Tryptophan