AUTHOR=Wang Yifei , Liu Yuqing , Chen Miao , Liu Danping , Shen Chen 

TITLE=CHN1 as a potential predictive genetic biomarker for atopic dermatitis-related depression

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1677275

DOI=10.3389/fimmu.2025.1677275

ISSN=1664-3224

ABSTRACT=IntroductionThe comorbidity of atopic dermatitis (AD) and depression has garnered increased attention in recent years, yet the immunopathological mechanisms underlying this connection remain unclear. To bridge this gap, the study aimed to uncover the immune regulatory networks and identify key genetic markers involved in the comorbidity of depression in AD.MethodsWe performed RNA sequencing on peripheral blood mononuclear cells (PBMCs) collected from 20 AD patients with and without depression. By integrating bioinformatics analyses with machine learning, we conducted weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and employed machine learning models of least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). Additionally, validation was carried out in an independent cohort of 20 participants to confirm the expression of the identified potential pivotal gene.ResultsA total of 394 differentially expressed genes (DEGs) were identified in AD patients with depression as compared to those non-depressed counterparts. Weighted gene co-expression network analysis (WGCNA) pinpointed a pink module encompassing 83 genes strongly linked to depressive symptoms. Functional enrichment analysis highlighted biological processes related to neurotransmitter uptake and the negative regulation of T-helper (Th) 17 cell differentiation. Furthermore, machine learning models of least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) consistently identified CHN1 as a potential pivotal gene upregulated in AD patients with depression. The expression level of CHN1 demonstrated positive correlation with Th2 and Th17 cytokine signatures, as well as with the Hospital Anxiety and Depression Scale-Depression (HADS-D) score, and the Eczema Area and Severity Index (EASI). Validation in an independent cohort of 20 participants confirmed the significant upregulation of CHN1 in depressed AD patients.DiscussionTogether, these findings reveal previously unrecognized immunoinflammatory axis underlying AD-associated depression, and shed light on CHN1 as a potential molecular bridge connecting peripheral inflammation and neuropsychiatric manifestations.