An atopic dermatitis mouse model reveals potential utility for atopic dermatitis-generated comorbid depression brain circuitry studies

Chronic atopic dermatitis (AD) affects millions globally and has an alarming propensity to generate comorbid chronic depression. Currently, no effective therapies exist specifically for AD-generated comorbid depression (ADCD), likely due to unknown itch- and affect-processing brain mechanisms and inadequate preclinical models. Hence, there is a critical need for a suitable pre-clinical research model that can be used to study ADCD’s unique pathophysiology. In this investigation, we searched for preclinical models of ADCD by evaluating previously established house dust mite-induced (HDM model) and MC903-induced (MC903 model) AD mouse models for comorbid depression-like features. Using the elevated plus maze, forced swim test, scratching behavior assays, histology, and clinical skin scoring, we show that the HDM model lacks significant anxiety-like (p = 0.858, student’s t-test) and depression-like behavior (p = 0.0512), but develops an AD-like skin pathology with strong scratching behavior (p < 0.005). By contrast, the MC903 model uniquely displays not only a more robust AD-like skin pathology, but also concomitantly significant scratching bouts (p < 0.0001), scratching duration, (p = 0.047), anxiety-like (p = 0.0367) and depression-like (p = 0.0256) behavior, and a greater state of stress (p < 0.005) indicated by serum corticosterone ELISA. Ultimately, our investigation reveals that both models faithfully recapitulate human AD pathology features, but only the MC903 model generated concomitant ADCD-like features. Using the MC903 model, future investigations will explore itch- and affect-processing brain regions for structural and functional hallmarks of the depression-like state and identify potential circuit-based therapeutic targets for treating this comorbidity.