Metabolomic Identification of Serum Exosome-Derived Biomarkers for Bipolar Disorder

Abstract

Background. Exosomes are extracellular vesicles that play important roles in various physiological and pathological functions. Previous studies have demonstrated that exosome-derived contents are promising biomarkers to inform the pathogenesis and diagnosis of major depressive disorder and schizophrenia. Methods. We used ultraperformance liquid chromatography-tandem mass spectrometry to analyze the differentially expressed metabolites in serum exosomes of patients with bipolar disorder (BD) and evaluated the potential of exosomal metabolites as biomarkers for BD. Results. Our results showed 26 differentially expressed serum exosomal metabolites in patients with BD ( n = 32 ) when compared with healthy control (HC) subjects ( n = 40 ), and these differentially expressed metabolites were enriched in pathways related to sugar metabolism. We then utilized random forest classifier and identified 15 exosomal metabolites that can be used to classify samples from patients with BD and HC subjects with 0.838 accuracy (95% CI, 0.604–1.00) in the training set of participants. These 15 metabolites showed excellent performance in differentiating between patients with BD and HC subjects in the testing set of participants, with 0.971 accuracy (95% CI, 0.865–1.00). Importantly, the 15 exosomal metabolites also showed good to excellent performance in differentiating between BD patients and other major psychiatric diseases (major depressive disorder and schizophrenia). Conclusion. Collectively, our findings for the first time revealed a potential role of exosomal metabolite dysregulations in the onset and/or development of BD and suggested that blood exosomal metabolites are strong candidates to inform the diagnosis of BD.

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

“…Several bioreactions have been revealed to exhibit great importance during the pathogenesis, including galactose biochemical processing, amino sugar and nucleotide sugar reactions, and the mutual interconversion between pentose and glucuronic acid. 73 This is consistent with a previous study of multi-pathway alterations in BD plasma metabolomics. 97 This has strongly suggested that the dysfunction of glucose metabolism is closely related to the occurrence and deterioration of BD.…”

“…Serum-derived EVs are essential not only for bipolar disorder research, 73 they also provide anti-inflammatory substances and antibiotics to COVID-19 patients, 74 as well as in Alzheimer’s disease. 50 , 75 Due to the complexity of whole blood substances, blood-derived EVs are rarely used.…”

“… Diagnosis Late myocardial necrosis of atherosclerotic Adipose tissue C16:0 ceramide and their derivatives [ 87 ] Acute pancreatitis Plasma Eicosatrienoic acid (C20:3), thiamine triphosphate. 2-Acetylfuran, cis-Citral [ 68 ] Gestational hypertension Plasma SM, acetyl CoA, methionine, phenylalanine, tryptophan, carotenoids, tyrosine, arginine, leucine [ 88 ] ST elevation myocardial infarction Plasma Ceramides, dihydroceramides, and sphingomyelins [ 69 ] Lung cancer Pleural effusions Phenylalanine, leucine, PC 35:0 and SM 44:3 [ 91 ] Serum Ceramides, PC and polyunsaturated acyl chains [ 92 ] Prostate cancer Urinary PS 18:1/18:1 and lactosylceramide (d18:1/16:0) [ 93 ] Benign prostate hyperplasia Urinary PC, PE, SM [ 31 ] Bipolar disorder Serum lysoPE 18: 0, lysoPE 14: 0, lysoPC 18: 0, and lysoPC 20: 1 [ 73 ] Schizophrenia Depressive disorder Chromochromic leukogystrophy …”

Alterações Neuropsicológicas no Transtorno Bipolar

“…Para a análise desse fator é utilizado o cérebro pós morte e amostras de sangue (Andreazza, et al, 2015). Outro parâmetro que está sendo investigado para o possível diagnóstico de TB, são as desregulações de metabólitos exossomais no início ou desenvolvimento do TB, indicando assim que os metabólitos exossomais sanguíneos são fortes candidatos para informar o diagnóstico de TB (Du, et al, 2022). Diante dos dados expostos acima, o tratamento do TB ainda é considerado um desafio grande, uma vez que é preciso debelar qualquer episódio agudo e evitar que novos ocorram.…”

Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder

“…Metabolomics is a discipline to obtain all information of metabolites in a biological sample and would give mechanistic insights into the etiology of DD ( Nedic Erjavec et al, 2018 ; Du et al, 2022 ). For example, nine potential biomarkers involved the depression pathogenesis were identified based on metabolomics analysis by comparing the rats’ serum metabolites of CUMS(chronic unpredictable mild stress) model group and Xiao-Chai-Hu-Tang group ( Xiong et al, 2016 ).…”