Depression and Inflammatory Skin Disease: Collaborative New Findings

Emma Guttman, MD, PhD, chair of Dermatology at the Icahn School of Medicine at Mount Sinai, and James Murrough, MD, PhD, vice chair for Clinical Research in Psychiatry at Mount Sinai, discussed their recent research collaboration linking inflammatory pathways in atopic dermatitis to the pathophysiology of major depressive disorder (MDD).¹

Guttman described how the collaboration began when Murrough's group identified elevated cytokines—particularly IL-17–related molecules—in patients with treatment-resistant depression. Guttman broadened this investigation to include a comprehensive cytokine panel and comparison against both psoriasis and atopic dermatitis. The key finding was that type 2 cytokines, including IL-13, were markedly elevated in MDD patients, mirroring the immune signature seen in eczema rather than psoriasis. This prompted investigators to model whether dupilumab—a biologic targeting IL-4 and IL-13 signaling—might reverse the abnormal immune phenotype observed in depression.

Murrough contextualized these findings within the broader field, noting that while inflammation's role in depression had long been hypothesized, the specific immune perturbations underlying MDD remained poorly characterized.² He emphasized that MDD is likely biologically heterogeneous, stating: "it might be that different perturbations in the immune system are relevant for the treatment of different subpopulations of patients." A clinical trial of dupilumab in MDD is now planned, with endpoints including symptom response, peripheral immune biomarkers, and functional MRI measures of relevant brain circuits.

Both experts addressed the safety profile of dupilumab, with Guttman noting that, unlike most biologics, the FDA does not require blood work monitoring even in pediatric patients. She characterized biologics not as immunosuppressants but as "immune correctors." Murrough drew a parallel to early resistance encountered when studying ketamine for depression, arguing: "chronic refractory depression is a serious brain disorder—people die by suicide."

The investigators also discussed the clinical implications of reconceptualizing comorbid depression in inflammatory skin disease as potentially mechanistic rather than purely reactive, advocating for lower referral thresholds to psychiatry among dermatology colleagues. Working groups developing DSM-6 are reportedly considering formal recognition of an inflammatory subtype of MDD, underscoring the translational significance of this line of inquiry, Murrough pointed out.

Dr Guttman is a professor and chair of Dermatology at the Icahn School of Medicine at Mount Sinai.

Dr Murrough is a professor and vice chair for Clinical Research in Psychiatry at the Ichan School of Medicine at Mount Sinai.

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. 2026.

2. Hebebrand M. Study links depression to atopic dermatitis-related immune signature. Dermatology Times. February 13, 2026. Accessed March 27, 2026. https://www.dermatologytimes.com/view/study-links-depression-to-atopic-dermatitis-related-immune-signature