Biomarkers of bipolar disorder based on metabolomics: A systematic review

Bipolar disorder (BD) is a severe affective disorder characterized by recurrent episodes of depression or mania/hypomania, which significantly impair cognitive function, life skills, and social abilities of patients. There is little understanding of the neurobiological mechanisms of BD. The diagnosis of BD is primarily based on clinical assessment and psychiatric examination, highlighting the urgent need for objective markers to facilitate the diagnosis of BD. Metabolomics can be used as a diagnostic tool for disease identification and evaluation. This study summarized the altered metabolites in BD and analyzed aberrant metabolic pathways, which might contribute to the diagnosis of BD. Search of PubMed and Web of science for human BD studies related to metabolism to identify articles published up to November 19, 2022 yielded 987 articles. After screening and applying the inclusion and exclusion criteria, 16 untargeted and 11 targeted metabolomics studies were included. Pathway analysis of the potential differential biometabolic markers was performed using the Kyoto encyclopedia of genes and genomes (KEGG). There were 72 upregulated and 134 downregulated biomarkers in the untargeted metabolomics studies using blood samples. Untargeted metabolomics studies utilizing urine specimens revealed the presence of 78 upregulated and 54 downregulated metabolites. The targeted metabolomics studies revealed abnormalities in the metabolism of glutamate and tryptophan. Enrichment analysis revealed that the differential metabolic pathways were mainly involved in the metabolism of glucose, amino acid and fatty acid. These findings suggested that certain metabolic biomarkers or metabolic biomarker panels might serve as a reference for the diagnosis of BD.