Could Dupilumab Treat Depression? Mount Sinai Study Targets Immune Link

Researchers at the Icahn School of Medicine at Mount Sinai are investigating a potential immunologic link between atopic dermatitis and major depressive disorder (MDD), with early findings suggesting that type 2 cytokines—long associated with atopic inflammation—may also play a significant role in the pathophysiology of depression.

The collaboration between Emma Guttman, MD, PhD, chair of the Department of Dermatology, and James Murrough, MD, PhD, vice chair for clinical research in the Department of Psychiatry, began when Murrough's team identified elevated inflammatory cytokines in the blood of patients with treatment-resistant depression. Rather than limiting the comparison to psoriasis, which had been the field's prior reference point due to elevated IL-17, Guttman proposed expanding the analysis to include both psoriasis and atopic dermatitis, representing opposing poles of the immune axis and broadening the cytokine panel examined.

The results were notable. Although IL-17 was modestly elevated, IL-13 and other type 2 cytokines were substantially increased in patients with MDD, a signature more consistent with atopic dermatitis than psoriasis. Using computational modeling, the team extrapolated that dupilumab, the IL-4/IL-13 receptor antagonist approved for atopic dermatitis and other type 2–driven conditions, could theoretically normalize up to 100% of the observed immune phenotype in patients with depression.

Murrough noted that these findings have now supported a funded clinical trial to prospectively evaluate dupilumab in patients with MDD who do not have a co-occurring inflammatory skin disease. The study will assess symptomatic improvement, changes in circulating immune markers, and modulation of mood-relevant brain circuits using functional MRI—work supported in part by the Wellcome Trust.

Beyond the specific trial, both researchers framed the findings within a broader vision for psychiatry: the development of biologically defined subtypes of MDD and, ultimately, point-of-care blood tests that could guide treatment selection. Currently, no validated biological subtype of any psychiatric disorder exists, and antidepressant prescribing remains largely empirical. Murrough noted that working groups for the Diagnostic and Statistical Manual of Mental Disorders (Sixth Edition) are actively discussing whether sufficient data exists to formally define an inflammatory subtype of depression.

Guttman and Murrough also addressed the clinical tendency to characterize depression in patients with inflammatory skin disease as reactive—a psychological consequence of chronic illness. Both researchers cautioned against this framing, arguing that shared immunologic mechanisms may underlie co-occurrence, with implications for screening thresholds and referral practices across specialties.

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