Abstract
Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine’s mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated by many patients, intranasal glutathione warrants further study as potential therapy in Skin Picking, trichotillomania and other body-focused repetitive behavior disorders.
Highlights
Mice with Ulcerative Dermatitis (UD) can scratch deep skin lesions across large portions of their bodies
While UD has been well studied in the veterinary literature for these reasons [2,3,4], it has recently been proposed as a potential model of Skin Picking Disorder in humans [5]
Mouse strains prone to UD tend to be prone to ‘barbering’ which has been validated as a model of trichotillomania [8], and the two behaviors share at least some common mechanisms in mice [5]
Summary
Mice with Ulcerative Dermatitis (UD) can scratch deep skin lesions across large portions of their bodies. Ongoing work in our lab suggests a primary role for oxidative stress in barbering and UD [12] It is unclear whether oxidative stress may be acting peripherally or proprioceptively to drive abnormal grooming behavior (e.g. via itch), or whether oxidative stress is acting centrally in the brain. To address these issues, and to begin to separate these mechanistic possibilities, we treated mice with two leading antioxidant therapies: systemic (oral) NAC, and intranasal glutathione (GSH). We have argued that the efficacy of NAC in treating compulsive hair pulling in humans (trichotillomania), and in mice (barbering), reflects its role as precursor to GSH synthesis in the brain [12]. Direct intranasal administration of GSH is a further test of this hypothesis
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