title: Tryptophan Metabolism and White Matter Integrity in Schizophrenia.
abstract: Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (p<0.001), and kynurenine/tryptophan ratios were correspondingly higher (p=0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r=0.347, p=0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r=-0.391 and -0.350 respectively, p=0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chiappelli
authors.affiliation: Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.|MIRECC, VISN 5, Baltimore, MD, USA.|Rocky Mountain MIRECC for Suicide Prevention, Denver, CO, USA.
authors.forename: Teodor T
authors.initials: TT
authors.lastname: Postolache
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rowland
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S Andrea
authors.initials: SA
authors.lastname: Wijtenburg
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Shukla
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Malle
authors.initials: M
authors.lastname: Tagamets
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Savransky
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Adem
authors.initials: A
authors.lastname: Can
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016880:Anisotropy; D056324:Diffusion Tensor Imaging; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D014364:Tryptophan / Q000378:metabolism*; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007737:Kynurenine; D018698:Glutamic Acid; D014364:Tryptophan