Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case–control study
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Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty-five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography–tandem mass spectrometry (LC–MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, l-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia.
KeywordsAmino acid Schizophrenia Targeting profiles Liquid chromatography–mass spectrometry Metabolomics
This work was supported by Peking University Health Science Center Medical Cross Disciplinary Fund (BMU20140435). We thank Dr. Chuanbo Zhang and other medical staff from Weifang Mental Health Center for their assistance with subject recruitment, follow up and blood sample collection. Beijing Omics Bio-tech Co., Ltd for their kind help in data collection for this study.
JYW, BC, and DFW conceived and designed the study; BC, DFW, JZ, and NHH collected the data and performed the statistical analysis; BC, ZHP, EB, RSM, JYW, DFW, DC, and JDR contributed to the discussion; and JYW, ZHP, RSM, EB, MS, RBM, JDR, HZ, YQL, and QX revised the paper. All authors have read and approved the final version of this article.
This work was supported by the Medicine Interdisciplinary Seed Fund (BMU20140435) by Health Science Center, Peking University.
Compliance with ethical standards
Conflict of interests
The authors declare no conflict of interests.
This study was reviewed and approved by the Ethics Review Committee of Public Health at Peking University Health Science Center (IRB00001052-14071).
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