Kynurenine pathway metabolites and therapeutic response to olanzapine in female patients with schizophrenia: A longitudinal study

Abstract

Aim: A metabolomics approach has recently been used to identify metabolites associated with response to antipsychotic treatment. This study was designed to identify the predictive biomarkers of response to olanzapine monotherapy using a metabolomics-based strategy. Methods: Twenty-five first-episode and drug-naïve female patients with schizophrenia were recruited and treated with olanzapine for 4 weeks. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and 4-week follow-up. Results: Positive subscore, general psychopathology subscore, and PANSS total score were significantly decreased after treatment. An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach identified 72 differential metabolites after treatment. In addition, the baseline levels of methyl n-formylanthranilate (MNFT) were correlated with the rate of reduction in the positive subscore or PANSS total score. However, increase in MNFT after treatment was not associated with the rate of reduction in the PANSS total score or its subscores. Subsequent regression analysis revealed that the baseline MNFT levels predicted the treatment outcomes after olanzapine monotherapy for 4 weeks in patients with schizophrenia. Conclusions: Our study results suggest that the baseline MNFT levels in the kynurenine pathway of tryptophan metabolism may be predictive of the treatment response to olanzapine in schizophrenia.