Discovery of serum metabolomics characterization in patients with generalized anxiety disorder based on LC-MS

Abstract

The pressure on people’s lives and work is increasing with the continuous development of modern society, and generalized anxiety disorder (GAD) has become a relatively common psychological problem. Nevertheless, the pathological mechanisms underlying anxiety disorders remain poorly understood, and specific biomarkers available for identification and clinical diagnosis are still lacking. Serum samples were collected from 20 patients with GAD and 20 healthy controls. Untargeted metabolomics based on liquid chromatography-mass spectrometry (LC-MS) was used for detection and analysis to screen differential metabolites and perform correlation analyses. Compared with those in healthy controls, a total of 1271 differential metabolites were identified in patients with GAD, including 986 upregulated metabolites and 285 downregulated metabolites. Among all the identifiable metabolite classes, the top six categories were lipids and lipid-like molecules (32.53%), organic acids and derivatives (15.12%), organoheterocyclic compounds (13.95%), benzenoids (5.81%), fatty acids (4.65%), and amino acids and peptides (4.65%). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed 11 significantly different metabolic pathways, including those related to choline metabolism in cancer, glutamatergic synapse, and GABAergic synapses. We performed receiver operating characteristic (ROC) curve analysis and correlation analysis between differential metabolites and disease duration, sex, age, and scale scores. The results revealed that 16-hydroxypalmitic acid and 2-hydroxypalmitic acid were closely correlated with Self-Rating Anxiety Scale(SAS) scores. This study preliminarily investigated the differences in serum metabolites between patients with GAD and healthy controls, providing a reference for the clinical diagnosis and relevant research of GAD. This study is registered in the International Traditional Medicine Clinical Trial Registry (Registration number: ITMCTR2025000970; Registration date: January 12, 2025).