Researchers from the Departments of Psychiatry and Dermatology at the Icahn School of Medicine at Mount Sinai have found that major depressive disorder shares immune abnormalities with inflammatory skin diseases, particularly the Th2 immune pathway implicated in atopic dermatitis. The findings, published February 11 in Molecular Psychiatry, suggest new therapeutic possibilities for treating psychiatric illness by targeting immune pathways already successfully addressed in dermatology.
The team compared blood proteomic profiles of patients with major depressive disorder to those with atopic dermatitis, psoriasis, and healthy controls. They found that the proteomic profiles of patients with major depressive disorder share Th2 pathway dysregulation with those who have atopic dermatitis. Specifically, the research identified dysfunction in the interleukin-4 receptor alpha (IL-4R alpha), a cell receptor known to play a key role in regulating inflammation. Dr. James Murrough, Director of the Dennis S. Charney, MD, Depression and Anxiety Discovery Center, explained that the team’s computational analysis “identified dupilumab, which targets the IL-4 receptor alpha subunit and thus inhibits the Th2 axis, as significantly affecting the major depressive disorder signature by reversing the dysregulation of several inflammatory proteins related to Th2 signaling.”
Dupilumab (Dupixent) is an existing monoclonal antibody already approved by the U.S. Food and Drug Administration for treating moderate-to-severe atopic dermatitis. Animal studies supported these findings: neutralization of IL-4R alpha with a monoclonal antibody prevented stress-induced social avoidance behavior in stress-susceptible mice following chronic social defeat stress, a mouse model of depression. “This study is exciting because it opens the possibility of a completely new way to treat depression by targeting the immune system, as opposed to more traditional antidepressants that target neurotransmitters in the brain,” Dr. Murrough said.
The Mount Sinai research team recently received a nearly $1 million grant from Wellcome to investigate whether dupilumab can reverse the immune changes seen in major depressive disorder patients and improve depressive symptoms. A new clinical trial will soon launch to test whether targeting the Th2 pathway with dupilumab can improve depressive symptoms for patients with major depressive disorder. The Icahn School of Medicine at Mount Sinai filed a provisional patent application in 2025 based on these findings.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.newswise.com/articles/major-depressive-disorder-shares-immune-abnormalities-and-potential-therapeutic-targets-with-inflammatory-skin-diseases-according-to-new-study/?sc=rsla