Chiappelli Joshua, Postolache Teodor T, Kochunov Peter, Rowland Laura M, Wijtenburg S Andrea, Shukla Dinesh K, Tagamets Malle, Du Xiaoming, Savransky Anya, Lowry Christopher A, Can Adem, Fuchs Dietmar, Hong L Elliot
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Neuropsychopharmacology. 2016 Sep;41(10):2587-95. doi: 10.1038/npp.2016.66. Epub 2016 May 4.
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.
精神分裂症与白质结构和功能异常有关，但其潜在的神经病理学尚不清楚。我们推测，犬尿氨酸途径中色氨酸降解增加可能与白质微观结构和生物化学有关，这可能导致精神分裂症患者的白质异常。为了验证这一点，我们从37例精神分裂症患者和38例健康对照者中获取空腹血浆样本，评估总色氨酸及其代谢产物犬尿氨酸的水平。犬尿氨酸与色氨酸的比值被用作该途径中色氨酸分解代谢活性的指标。通过扩散张量成像（DTI）和氢磁共振波谱（MRS）评估白质结构和功能。与对照组相比，患者的色氨酸水平显著降低（p<0.001），犬尿氨酸/色氨酸比值相应升高（p=0.018）。在患者中，血浆色氨酸水平较低与较低的结构完整性（DTI分数各向异性）相关（r=0.347，p=0.038）。在患者和对照组中，犬尿氨酸/色氨酸比值均与额叶白质谷氨酸水平呈负相关（分别为r=-0.391和-0.350，p=0.024和0.036）。这些结果提供了初步证据，表明色氨酸/犬尿氨酸途径异常活动与精神分裂症患者白质完整性变化和白质谷氨酸有关。
