Study Links Depression to Atopic Dermatitis–Related Immune Signature

A new translational study from investigators at the Icahn School of Medicine at Mount Sinai is drawing attention to an immune pathway more commonly associated with dermatology than psychiatry. In findings published in Molecular Psychiatry, researchers report that the serum proteomic profile of patients with major depressive disorder (MDD) shares key immune abnormalities with inflammatory skin diseases—most notably activation of the T helper 2 (Th2) immune axis implicated in atopic dermatitis.¹

The work adds to a growing body of literature suggesting that depression, long conceptualized primarily as a disorder of neurotransmission, may also involve clinically meaningful immune dysregulation. For practicing clinicians, the study is noteworthy not only for its mechanistic implications but also for its therapeutic ambition: The team is preparing to test whether dupilumab, an FDA-approved biologic for atopic dermatitis that targets IL-4 receptor α (IL-4Rα), can improve depressive symptoms in patients with MDD.

Immune Signatures in Depression

MDD affects millions of individuals worldwide and remains refractory to treatment in a substantial proportion of patients. Although monoaminergic antidepressants remain first-line therapy, increasing evidence supports bidirectional communication between the immune system and the central nervous system in stress-related disorders.

“A large number of studies have described immune changes related to depression, but few clinical studies have tested the efficacy of anti-inflammatory drugs in reducing symptoms of it,” a news release from Mount Sinai noted.² Elevated inflammatory markers, altered cytokine profiles, and immune cell shifts have all been described in subsets of patients with MDD. However, translating these findings into targeted, disease-modifying interventions has proven difficult.

In contrast, dermatology has seen rapid progress over the past decade. Disease immunophenotyping in conditions such as psoriasis and atopic dermatitis has led to targeted biologic therapies that substantially alter disease trajectory. Dupilumab (Dupixent; Sanofi and Regeneron), a monoclonal antibody directed against the IL-4Rα subunit, inhibits signaling of IL-4 and IL-13—key drivers of the Th2 pathway—and was the first FDA-approved long-term biologic for moderate to severe atopic dermatitis.

Cross-Disciplinary Approach

Seeking to apply a similar translational model to psychiatry, the Mount Sinai team assembled experts from psychiatry, dermatology, and neuroscience. “Given the successful translational approach in dermatology, where disease immunophenotyping led to advances in understanding pathogenesis and expansion of the therapeutic pipeline, we put together a cross-disciplinary team…to assess the viability of a targeted treatment approach in [MDD],” said James Murrough, MD, PhD, director of the Dennis S. Charney, MD, Depression and Anxiety Discovery Center and corresponding co–senior author.

The investigators first compared blood proteomic profiles from patients with MDD with those from patients with atopic dermatitis, psoriasis, and healthy controls. They found that patients with MDD exhibited Th2 pathway skewing and dysregulation of immune and neurovascular-related proteins similar to patterns seen in atopic dermatitis.

This overlap suggested a potentially actionable pathway. To explore therapeutic implications, the team conducted an in silico drug repurposing analysis. Using computational modeling, they examined whether biologic agents commonly used in dermatology might reverse the dysregulated proteomic signature observed in MDD.

“This computational approach identified dupilumab as significantly affecting the [MDD] signature by reversing the dysregulation of several inflammatory proteins related to Th2 signaling,” Murrough said. “Stemming directly from our findings, our team will soon launch a new clinical trial to investigate whether targeting the Th2 pathway with dupilumab can improve depressive symptoms for patients with [MDD].”

Preclinical Validation

To complement the proteomic and computational data, the investigators turned to a well-established mouse model of depression: chronic social defeat stress. In stress-susceptible mice, neutralization of IL-4Rα with a monoclonal antibody prevented the development of stress-induced social avoidance behavior, a commonly used behavioral correlate of depressive-like states.

Although animal models cannot fully replicate the complexity of human depression, the findings offer biological plausibility that Th2 signaling may contribute to stress-related behavioral changes.

Clinical Implications and Next Steps

The research team has received a nearly $1 million grant from Wellcome to investigate whether dupilumab can reverse immune changes in patients with MDD and improve depressive symptoms. Murrough will lead the trial alongside Mina Rizk, MD, an assistant professor of psychiatry at Mount Sinai.

“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,” Murrough said.

Emma Guttman-Yassky, MD, co–senior author and the Waldman Professor of Dermatology and Immunology and Health System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine, emphasized the broader translational implications. “We are thrilled that the successful translational approach in dermatology may also be an effective strategy for patients who face [MDD] and other psychiatric conditions,” she said. “These study findings provide a strong foundation and justification for human studies and clinical trials that directly address this new drug target.”

The Icahn School of Medicine at Mount Sinai has filed a provisional patent application based on these findings.

For clinicians, the work does not yet change practice. Dupilumab remains approved for dermatologic and allergic indications, and its safety, efficacy, and cost-effectiveness in MDD remain to be established. Nevertheless, the study underscores a shift in psychiatric research toward biologically stratified, immune-informed treatment strategies—an approach that may ultimately expand options for patients whose depression has not responded to conventional therapies.

References

1. He H, Cathomas F, Parise LF, et al. Major depressive disorder shares systemic immune signatures and potential therapeutic targets with inflammatory skin diseases. Mol Psychiatry. Published online February 11, 2026. doi:10.1038/s41380-025-03383-5
2. Major depressive disorder shares immune abnormalities and potential therapeutic targets with inflammatory skin diseases, according to new study. News release. Mount Sinai. February 11, 2026. Accessed February 12, 2026. https://www.mountsinai.org/about/newsroom/2026/major-depressive-disorder-shares-immune-abnormalities-and-potential-therapeutic-targets-with-inflammatory-skin-diseases-according-to-new-study