Talha Ağaç, Fatmanur Köktaşoğlu, Halime Dulun Ağaç, Metin Demirel, Şahabettin Selek, Somer Bekiroğlu, Mustafa Solmaz
This pilot study annotated exploratory urinary metabolic alterations in treated patients with BD during a manic episode. These findings are hypothesis-generating and require validation in larger, longitudinal, independent cohorts.
BACKGROUND: Bipolar disorder is a chronic psychiatric condition characterised by recurrent manic, hypomanic, and depressive episodes. Despite its substantial burden, Bipolar disorder lacks validated biological biomarkers, and diagnosis continues to rely on subjective clinical assessment. Urinary metabolomics-based nuclear magnetic resonance spectroscopy offers a non-invasive approach to characterising systemic metabolic alterations associated with psychiatric illness.
AIMS: This study aimed to annotate urinary metabolic alterations and dysregulated metabolic pathways in patients with Bipolar disorder during a manic episode, compared with healthy controls, using an untargeted H1NMR metabolomics approach.
METHODS: First-morning urine samples were collected from 19 patients experiencing a manic episode and 27 healthy controls. Metabolite annotation was supported by one- and two-dimensional NMR spectroscopy and database matching. Between-group differences were assessed using the limma moderated t-test with Benjamini-Hochberg false discovery rate correction. Multivariate analyses included principal component analysis, PERMANOVA, and exploratory orthogonal partial least-squares discriminant analysis. Pathway enrichment and topology analysis were performed using MetaboAnalyst 6.0.
RESULTS: After FDR correction, uracil and taurine were significantly decreased in the manic episode group. Pathway analysis annotated five significantly enriched pathways: taurine and hypotaurine metabolism, primary bile acid biosynthesis, pyrimidine metabolism, pantothenate and CoA biosynthesis, and β-alanine metabolism. Multivariate analyses revealed a statistically significant but modest group-related metabolic difference, with limited discriminatory performance in OPLS-DA modelling.
CONCLUSION: This pilot study annotated exploratory urinary metabolic alterations in treated patients with BD during a manic episode. These findings are hypothesis-generating and require validation in larger, longitudinal, independent cohorts.