Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.
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, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-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, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate.


CONCLUSIONS
The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients.


CONCLUSIONS
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.
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan; Department of CNS Research, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Noriko
N
Yoshimi
Department of CNS Research, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Takashi
T
Futamura
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Keiji
K
Kakumoto
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Alireza M
AM
Salehi
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Carl M
CM
Sellgren
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
Jessica
J
Holmén-Larsson
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
Joel
J
Jakobsson
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
Erik
E
Pålsson
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mikael
M
Landén
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Kenji
K
Hashimoto
Arginine; Bipolar disorder; N-acetylglutamic acid; Pyruvate; Serine; β-alanine