Sex and race differences of cerebrospinal fluid metabolites in healthy individuals

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作   者：

Reavis, Zackery W.;  Mirjankar, Nikhil;  Sarangi, Srikant;  Boyle, Stephen H.;  Kuhn, Cynthia M.;  Matson, Wayne R.;  Babyak, Michael A.;  Matson, Samantha A.;  Siegler, Ilene C.;  Kaddurah-Daouk, Rima;  Suarez, Edward C.;  Williams, Redford B.;  Grichnik, Katherine;  Stafford-Smith, Mark;  Georgiades, Anastasia; 

作者机构：

Dept Pharmacol & Canc Biol;  Dept Anesthesiol;  MA USA;  Ixcela Internal Fitness TM Co;  Amer Anesthesiol;  NC USA;  Dept Psychiat Behav Sci;  Durham;  Duke Univ;  FL USA;  Sunrise;  Box 3454 DUMC;  Sch Med;  Dept Psychiat & Behav Sci;  Bedford;  NC 27710 USA; 

关键词：

5-Hydroxyindoleacetic acid;  nervous system;  Sex;  Race;  Tryptophan pathway;  Monoamine metabolites;  Kynurenine;  Central;  Cerebrospinal fluid;  Purine pathway;  Tyrosine pathway; 

期刊名称：

Metabolomics :

i s s n：

1573-3882

年卷期：

2021 年 17 卷 2 期

页   码：

摘   要：

IntroductionAnalyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown.ObjectiveOur objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men).MethodsCSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33=.0015).ResultsMultivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p<0.0001), uric acid (p<0.0001), and N-acetylserotonin (p=0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p=0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p=0.018), while white participants had significantly higher concentrations of kynurenine (p<0.0001), indoleacetic acid (p<0.0001), xanthine (p=0.001), alpha-tocopherol (p=0.007), cysteine (p=0.029), melatonin (p=0.036), and 7-methylxanthine (p=0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences.ConclusionSeveral of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.