Metabolomic Profiling Reveals Distinct Plasma Metabolic Signatures in Acne Patients with and without Depression.

BACKGROUND

Acne vulgaris is common and often accompanied by depression, but their linking mechanisms remain unclear. Metabolomic profiling helps identify biomarkers and perturbed pathways, so this study explores metabolic associations/pathways in acne comorbid with depression via untargeted metabolomics.

METHODS

Seventy-four acne patients were grouped by Patient Health Questionnaire-9 (PHQ-9) scores (≥10: depressive, n=21; <10: non-depressive, n=53). Their plasma was pretreated with cold methanol/acetonitrile, analyzed via Agilent 1290 Ultra-High Performance Liquid Chromatography (UHPLC)-AB Triple TOF 6600 Liquid Chromatography-Mass Spectrometry (LC-MS). Data were processed by XCMS; metabolites annotated via Human Metabolome Database (HMDB)/METLIN. Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used.

RESULTS

We identified differential metabolites using Fold Change (FC) analysis combined with statistical significance testing, defining those with FC > 1.5 (upregulated) or FC < 0.67 (downregulated) and p < 0.05 as significant. Volcano plots and hierarchical clustering heatmaps clearly visualize these metabolites, showing distinct clustering patterns that distinguish the two groups. OPLS-DA modeling further revealed 24 key differential metabolites (VIP > 1 and p < 0.05), including 16 in positive ion mode (eg, hypoxanthine, taurine, L-tryptophan) and 8 in negative ion mode (eg, L-ascorbic acid, palmitic acid). Notably, Clustering patterns aligned with these metabolites (eg, upregulated hypoxanthine, downregulated L-ascorbic acid), confirming reliable differences. KEGG annotated 41 core pathways, with protein digestion and absorption (lowest p-value, annotated with 7 key amino acids) as a top-ranked pathway. Five amino acid metabolism-related pathways were upregulated, indicating enhanced amino acid turnover in acne patients with depression; all metabolites in the protein digestion and absorption pathway were also upregulated in this group.

CONCLUSION

Hypoxanthine, taurine and branched-chain amino acids may be biomarkers for acne-depression comorbidity. Protein digestion/absorption could be a new prognostic marker/therapeutic target, with metabolic-neuroendocrine imbalance underlying the comorbidity.