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Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.


ABSTRACT: BACKGROUND:Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. METHODS:We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). RESULTS:After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, ?-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of ?-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, ?-alanine, serine, or arginine, but lithium administration significantly increased serum levels of ?-ketoglutarate. CONCLUSIONS:The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, ?-alanine, serine, and arginine in BD patients. GENERAL SIGNIFICANCE:The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

SUBMITTER: Yoshimi N 

PROVIDER: S-EPMC4832124 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

Yoshimi Noriko N   Futamura Takashi T   Kakumoto Keiji K   Salehi Alireza M AM   Sellgren Carl M CM   Holmén-Larsson Jessica J   Jakobsson Joel J   Pålsson Erik E   Landén Mikael M   Hashimoto Kenji K  

BBA clinical 20160403


<h4>Background</h4>Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD.<h4>Methods</h4>We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39).<h4>Results</h4>After multivariate logistic regression, serum levels of  ...[more]

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