Psychological Stress-Induced Pathogenesis of Alopecia Areata: Autoimmune and Apoptotic Pathways

Alopecia areata (AA) is an autoimmune dermatological disease with multifactorial etiology and is characterized by reversible hair loss in patches. AA may be closely related to emotional stress and influenced by psychological factors as part of its pathophysiology; however, its etiology remains predominantly unknown. This review aimed to elucidate the association between AA occurrence and the neuropeptide substance P (SP) and corticotropin-releasing hormone (CRH), which are secreted during emotional stress, and have been understood to initiate and advance the etiopathogenesis of AA. Therefore, this review aimed to explain how SP and CRH initiate and contribute to the etiopathogenesis of AA. To assess the etiopathogenesis of AA, we conducted a literature search on PubMed and ClinicalTrials.gov. Overall, several authors described interactions between the hair follicles (HFs) and the stress-associated signaling substances, including SP and CRH, in the etiology of AA; this was attributed to the understanding in that AA can occur without the loss of HFs, similar to that observed in hereditary hair loss with age. Most studies demonstrated that the collapse of "immune privilege" plays a crucial role in the development and exacerbation of the AA; nonetheless, a few studies indicated that substances unrelated to autoimmunity may also cause apoptosis in keratocytes, leading to the development of AA. We investigated both the autoimmune and apoptotic pathways within the etiology of AA and assessed the potential interactions between the key substances of both pathways to evaluate potential therapeutic targets for the treatment of AA. Clinical trials of marketed/unreviewed intervention drugs for AA were also reviewed to determine their corresponding target pathways.