Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case–control study

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...

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Published inAmino acids Vol. 50; no. 8; pp. 1013 - 1023
Main Authors Cao, Bing, Wang, Dongfang, Brietzke, Elisa, McIntyre, Roger S., Pan, Zihang, Cha, Danielle, Rosenblat, Joshua D., Zuckerman, Hannah, Liu, Yaqiong, Xie, Qing, Wang, Jingyu
Format Journal Article
LanguageEnglish
Published Vienna Springer Vienna 01.08.2018
Springer Nature B.V
Subjects
Adolescent
Adult
Age
Aged
Amino acids
Amino Acids - blood
Ammonia
Analytical Chemistry
Arginine
aspartic acid
Biochemical Engineering
Biochemistry
Biological Variation, Individual
Biomedical and Life Sciences
Biosynthesis
Body mass index
Body size
Case-Control Studies
Chromatography
cysteine
Derivatives
Diagnostic systems
Female
gamma-aminobutyric acid
Generalized linear models
Glutamine
Humans
hydrophilic interaction chromatography
kynurenine
Life Sciences
linear models
Liquid chromatography
Male
Mass spectrometry
Mass spectroscopy
Mental disorders
Metabolism
Middle Aged
Neurobiology
Neurotransmission
Neurotransmitters
Original Article
Ornithine
Pathophysiology
Proteomics
Sarcosine
sarcosines
Schizophrenia
Schizophrenia - blood
Sex
Statistical analysis
Statistical methods
Statistical models
tandem mass spectrometry
Taurine
Threonine
Tryptophan
Urea
urea cycle
Young Adult
γ-Aminobutyric acid
Schizophrenia
Metabolomics
Amino acid
Liquid chromatography–mass spectrometry
Targeting profiles
Online AccessGet full text
ISSN0939-4451
1438-2199
1438-2199
DOI10.1007/s00726-018-2579-6

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Abstract 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.
AbstractList 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.
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.
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.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.
Author Wang, Dongfang
Wang, Jingyu
Liu, Yaqiong
Cao, Bing
Zuckerman, Hannah
McIntyre, Roger S.
Brietzke, Elisa
Pan, Zihang
Cha, Danielle
Rosenblat, Joshua D.
Xie, Qing
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  organization: Mood Disorders Psychopharmacology Unit, Toronto Western Hospital, University Health Network
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  surname: Liu
  fullname: Liu, Yaqiong
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– sequence: 10
  givenname: Qing
  surname: Xie
  fullname: Xie, Qing
  organization: Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Medical and Health Analysis Center, Peking University
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  givenname: Jingyu
  surname: Wang
  fullname: Wang, Jingyu
  email: wjy@bjmu.edu.cn
  organization: Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Medical and Health Analysis Center, Peking University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29796929$$D View this record in MEDLINE/PubMed
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Copyright Springer-Verlag GmbH Austria, part of Springer Nature 2018
Amino Acids is a copyright of Springer, (2018). All Rights Reserved.
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ISSN 0939-4451
1438-2199
IngestDate Fri Jul 11 08:03:41 EDT 2025
Fri Jul 11 15:32:37 EDT 2025
Fri Jul 25 10:58:41 EDT 2025
Fri Jul 25 11:10:40 EDT 2025
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IsPeerReviewed true
IsScholarly true
Issue 8
Keywords Schizophrenia
Metabolomics
Amino acid
Liquid chromatography–mass spectrometry
Targeting profiles
Language English
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pubmed_primary_29796929
crossref_citationtrail_10_1007_s00726_018_2579_6
crossref_primary_10_1007_s00726_018_2579_6
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PublicationDate 20180800
2018-8-00
2018-Aug
20180801
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  year: 2018
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PublicationSubtitle The Forum for Amino Acid, Peptide and Protein Research
PublicationTitle Amino acids
PublicationTitleAbbrev Amino Acids
PublicationTitleAlternate Amino Acids
PublicationYear 2018
Publisher Springer Vienna
Springer Nature B.V
Publisher_xml – name: Springer Vienna
– name: Springer Nature B.V
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Snippet Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been...
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SubjectTerms Adolescent
Adult
Age
Aged
Amino acids
Amino Acids - blood
Ammonia
Analytical Chemistry
Arginine
aspartic acid
Biochemical Engineering
Biochemistry
Biological Variation, Individual
Biomedical and Life Sciences
Biosynthesis
Body mass index
Body size
Case-Control Studies
Chromatography
cysteine
Derivatives
Diagnostic systems
Female
gamma-aminobutyric acid
Generalized linear models
Glutamine
Humans
hydrophilic interaction chromatography
kynurenine
Life Sciences
linear models
Liquid chromatography
Male
Mass spectrometry
Mass spectroscopy
Mental disorders
Metabolism
Middle Aged
Neurobiology
Neurotransmission
Neurotransmitters
Original Article
Ornithine
Pathophysiology
Proteomics
Sarcosine
sarcosines
Schizophrenia
Schizophrenia - blood
Sex
Statistical analysis
Statistical methods
Statistical models
tandem mass spectrometry
Taurine
Threonine
Tryptophan
Urea
urea cycle
Young Adult
γ-Aminobutyric acid
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Title Characterizing amino-acid biosignatures amongst individuals with schizophrenia: a case–control study
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