CHN1 as a Potential Predictive Genetic Biomarker for Atopic Dermatitis-related Depression

Yifei WangYuqing LiuMiao ChenDanping LiuChen Shen^*

• Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, China

The comorbidity of Atopic Dermatitisatopic dermatitis (AD) and depression has garnered increasingincreased attention in recent years. Yet,, yet the immunopathological mechanisms underlying this connection remain unclear. To bridge this gap, we collected performed RNA sequencing on peripheral blood mononuclear cell samples cells (PBMCs) collected from 20 AD patients with and without depression, and performed RNA sequencing analysis.. By integrating bioinformatics andanalyses with machine learning techniques, we aimed to uncover the immune regulatory networks and identify key genetic markers for the depression comorbidity in AD patients. Our analysis revealed . A total of 394 differentially expressed genes (DEGs) in AD patients with depression as compared to those non-depressiondepressed counterparts. Weighted gene co-expression network analysis (WGCNA) pinpointed a pink module encompassing 83 genes strongly linked to depression.depressive symptoms. Functional enrichment analysis of critical module genes revealed significant enrichment scores inhighlighted 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 machines highlightedmachine-recursive figure elimination (SVM-RFE) models 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 familiessignatures, as well as with the Hospital Anxiety and Depression Scale-Depression (HADS-D) score, and the Eczema Area and Severity Index. (EASI). Validation experiments on clinical samples of in an additionalindependent cohort of 20 participants confirmed the significant upregulation of CHN1 in depressed AD patients. This study is the first to unveil the intricate inflammatory and immune pathwaysTogether, these findings reveal previously unrecognized immunoinflammatory axis underlying AD-associated depression, sheddingand shed light on the critical role of CHN1 as a potential molecular bridge connecting peripheral inflammation and neuropsychiatric symptomsmanifestations.