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Neuropsychopharmacology. 2016 Sep;41(10):2587-95. doi: 10.1038/npp.2016.66. Epub 2016 May 4.

Tryptophan Metabolism and White Matter Integrity in Schizophrenia.

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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.
MIRECC, VISN 5, Baltimore, MD, USA.
Rocky Mountain MIRECC for Suicide Prevention, Denver, CO, USA.
Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.


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.

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