A NEW study suggests that a subset of patients with major depressive disorder (MDD) share immune system abnormalities with inflammatory skin diseases, raising the possibility that biologic drugs used in dermatology could be repurposed to treat depression.
MDD is a leading cause of disability worldwide, yet its biological underpinnings remain incompletely understood. Growing evidence indicates that immune dysregulation plays a role in at least some patients, but clinical trials of broad anti-inflammatory therapies have produced mixed results. In contrast, targeted immunomodulatory biologics have transformed care for inflammatory skin conditions such as atopic dermatitis and psoriasis, offering a potential roadmap for precision approaches in psychiatry.
Immune Dysregulation in Major Depressive Disorder
In the new study, researchers compared blood proteomic profiles from patients with MDD, atopic dermatitis, psoriasis, and healthy controls. They found that individuals with MDD exhibited a pattern of immune activation resembling that seen in atopic dermatitis, particularly a skewing toward T helper 2 (Th2) immune responses. Several immune and neurovascular-related proteins were similarly dysregulated in both conditions, suggesting shared systemic inflammatory pathways.
The team then conducted an in-silico drug repurposing analysis to determine whether biologics commonly used in dermatology could counteract the molecular signature observed in MDD. The analysis highlighted dupilumab, a monoclonal antibody that targets the interleukin-4 receptor alpha (IL-4Rα) subunit and inhibits Th2 signalling, as a promising candidate. Computational modelling indicated that dupilumab could reverse multiple Th2-associated inflammatory abnormalities identified in patients with MDD.
To test this hypothesis experimentally, the researchers turned to a mouse model of chronic social defeat stress, a well-established paradigm for studying stress-induced depressive-like behaviours. Pharmacological inhibition of IL-4Rα prevented the development of stress-induced social avoidance, a core behavioural feature relevant to depression.
Targeting the Th2 Axis in Major Depressive Disorder
The findings provide converging molecular and preclinical evidence implicating the Th2 immune axis in MDD and support further investigation of targeted immunotherapies as potential disease-modifying treatments. The study also highlights the value of cross-disciplinary drug repurposing strategies, suggesting that advances in dermatology may help inform the next generation of precision treatments in psychiatry.
Reference
He H et al. Major depressive disorder shares systemic immune signatures and potential therapeutic targets with inflammatory skin diseases. Mol Psychiatry. 2026;doi: 10.1038/s41380-025-03383-5.
