Dataset Information

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, 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.

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

ACCESS DATA

Publications

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]

PMID: 27114925

Similar Datasets

Project description:Urea cycle disorders (UCDs) are a group of genetic metabolic conditions characterized by enzyme deficiencies responsible for detoxifying ammonia. Hyperammonemia, the accumulation of intermediate metabolites, and a deficiency of essential amino acids-due to a protein-restrictive diet and the use of ammonia scavengers-can increase the risk of infections, particularly during metabolic crises. While the underlying mechanisms of immune suppression are still being fully elucidated, hyperammonemia may impair the function of immune cells, particularly T cells and macrophages, inhibiting the proliferation of T cells and cytokine production. Arginine, which is essential for T-cell activation and function, may also be limited in these patients, and its depletion can increase their vulnerability to infections. Twenty-four UCD patients and 31 healthy donors were recruited for the study. Peripheral lymphocyte subset analysis, intracellular protein and cytokine staining, and proliferation assays were performed by flow cytometry. Amino acid levels were measured using the HPLC method. The UCD patients exhibited low lymphocyte-proliferation capacity in both proximal and distal defects in response to phytohaemagglutinin (PHA) and anti-CD2, anti-CD3, and anti-CD28 (CD-mix), which was lower than healthy controls. Proximal-UCD patients exhibited a significantly higher response for IFN-γ compared to both distal-UCD patients and healthy controls. The different amino acids in the culture medium were changed significantly in the groups. This study highlights significant immune dysfunctions in UCD patients, particularly impaired T-cell proliferation and altered amino acid metabolism. Proximal UCD patients exhibited a higher IFN-γ response, indicating a potential for hyperinflammation. Despite this, infection rates did not significantly differ between proximal UCD and distal UCD patients, although distal UCD patients had higher hospitalization rates. Amino acid analysis revealed distinct metabolic disruptions, emphasizing the complex interplay between metabolism and immune function. These findings suggest that UCDs cause profound immune alterations, necessitating further research to develop targeted therapeutic strategies.

Dataset Information

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

Background

Methods

Results

Conclusions

General significance

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets