Metabolic profiling reveals potential biomarkers and underlying signaling pathways involved in mindfulness-based...

Mindfulness-based cognitive therapy (MBCT) demonstrates significant efficacy in improving depressive symptoms and modulating metabolic profiles. However, the specific metabolite biomarkers and metabolic pathways underlying MBCT's therapeutic effects in adolescent depression remain unclear. This study aims to identify potential metabolite biomarkers and metabolic regulation pathways associated with MBCT improvement of adolescent depression. A global untargeted metabolomics approach was employed to analyze plasma samples from 35 adolescents with depression undergoing MBCT, 35 receiving conventional treatment (CT), and 30 age- and sex-matched healthy controls. MBCT significantly alleviated anxiety and depression symptoms of adolescent patients visualized by SDS, GAD-7, and SCL-90 scores (P < 0.0001). Untargeted metabolomics analysis revealed distinct metabolic profile changes in MBCT group compared to CT group, with 203 metabolites significantly upregulated and 186 significantly downregulated in MBCT group (P < 0.05). Notably, circulating levels of metabolites such as 10,11-epoxy-3-geranylgeranylindole and paspalicine showed marked increases (P < 0.05), whereas abundances of arachidonic acid and L-glutamic acid exhibited significant decreases (P < 0.05). KEGG pathway enrichment analysis indicated that the 186 downregulated metabolites were primarily enriched in pathways such as long-term depression, synaptic vesicle cycle, GnRH signaling, and aspartate and glutamate metabolism. Pearson's correlation analysis suggested that arachidonic acid level changes was significantly correlated with clinical improvement of SDS and SCL-90 scores (adjusted P < 0.05). ROC analysis revealed that a combination of five metabolites, including 10,11-epoxy-3-geranylgeranylindole, (1S,2R)-1-C-(indol-3-yl) glycerol 3-phosphate, paspalicine, FO 2546E, and FO 2546M, exhibited strong predictive potential for MBCT efficacy (AUC = 0.9061). These findings suggested that arachidonic acid involved in the long-term depression pathway may play pivotal roles in MBCT improvement of adolescent depression. This study provides insight into the potential biomarkers and metabolic regulation mechanisms underlying MBCT's therapeutic effects and theoretical guidance for clinical practice in MBCT intervention for adolescent depression. See also the graphical abstract(Fig. 1).