Neural hypothesis has become an important aspect of vitiligo, yet without corresponding diagnostic indicators. We preliminarily found 32 cases of vitiligo patients with certain aggregation of mental factors. In peripheral blood mononuclear cells (PBMCs) of these patients, transcriptome analyses revealed that the circulation expression of a type I interferon (IFN-I)-dependent genes was induced. Also, serum IFNα was elevated in vitiligo patients with depression. Therefore, our hypothesis is whether IFNα levels predict the occurrence of psychiatric vitiligo. Through the establishment of stress-induced depigmentation model, serum IFNα also showed increase. Intracerebroventricular and subcutaneous IFNα injection can both elicit not only depressive behavior but also vitiligo-like characteristics. Mechanistically, central IFNα induces the release of dorsal root ganglion (DRG) substance P (SP) to inhibit melanogenesis. Peripheral IFNα disturbs cutaneous microenvironment. Type I IFN (IFNα) pathway-related genes in stress vitiligo were significantly discriminating from non-stress vitiligo, while that of type II IFN pathway was not.
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