Chromatography-Driven Metabolomic Insights into the Acne–Depression Connection

While acne is often accompanied by depression, the linking mechanisms between both conditions remain unclear. Researchers fromSouthwest Medical University (Luzhou, China) and The First People's Hospital of Neijiang City (China) performed comprehensive metabolomic profiling of plasma samples from acne patients with and without comorbid depression. By employing advanced analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, the team hoped to identify unique metabolic signatures that characterize the interaction between acne and depression. A paper based on their efforts was published in Clinical, Cosmetic and Investigational Dermatology (1).

One of the world’s most prevalent dermatological conditions, acne vulgaris affects individuals across various age groups and ethnicities (2). Characteristics of the condition include the presence of comedones (clogged pores colloquially referred to as blackheads or whiteheads), inflammatory lesions, and, in severe cases, scarring (3-5).Approximately 85% of adolescents and young adults experience acne, with many of these cases persisting into adulthood (6,7).Acne is often associated with a variety of psychological distresses, including a lowered sense of self-esteem, anxiety, and depression (8).

“Few studies have systematically investigated the shared metabolic features of patients with both acne and depression,” said the researchers conducting this study, “leaving a significant gap in understanding the mechanisms of their comorbidity.” To address this gap, the team set out to perform comprehensive metabolomic profiling of plasma samples from acne patients with and without comorbid depression. “By employing advanced analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy,” they stated, “we seek to identify unique metabolic signatures that characterize the interaction between acne and depression. The findings are expected to reveal both shared and distinct metabolic pathways, provide potential biomarkers for early detection, and identify novel therapeutic targets. Ultimately, this study aims to bridge the gap between dermatological manifestations and psychiatric symptoms, promoting an integrated patient care approach that addresses both physical and mental health.” (1)

Seventy-four acne patients were grouped by Patient Health Questionnaire-9 (PHQ-9) scores, and their plasma was pretreated with cold methanol/acetonitrile before being analyzed with ultrahigh-pressure liquid chromatography (UHPLC)-MS. The researchers 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 visualized these metabolites, revealing distinct clustering patterns which distinguished the two groups. Orthogonal partial least squares-discriminant analysis (OPLS-DA) modeling further revealed 24 key differential metabolites (VIP > 1 and p < 0.05), including 16 in positive ion mode (including hypoxanthine, taurine, and L-tryptophan) and 8 in negative ion mode (including L-ascorbic acid and palmitic acid). Notably, clustering patterns aligned with these, confirming reliable differences. The Kyoto Encyclopedia of Genes and Genomes(KEGG) database 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 (1).

The findings from this research indicates that hypoxanthine, taurine, and branched-chain amino acids may be biomarkers for acne-depression comorbidity. Furthermore, protein digestion and absorption may be a new therapeutic target, with metabolic-neuroendocrine imbalance underlying the comorbidity (1).

“Collectively,” state the authors of the article, “these findings firmly establish abnormalities in the metabolic-neuroendocrine axis as the common pathological underpinning for this comorbidity, providing a transformative framework for the development of targeted interventions and personalized treatment strategies.” (1)

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References

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2. Williams, H. C.; Dellavalle, R. P.; Garner, S. Acne Vulgaris. Lancet 2012, 379 (9813), 361–372. DOI: 10.1016/S0140-6736(11)60321-8
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