From Dracula to The Adventures of Sherlock Holmes, psychosocial exposures that are perceived as stress have frequently been represented to cause hair loss and/or premature hair greying. Yet, skepticism abounds in the scientific literature that these phenomena are more than mere myths deeply rooted in popular culture (Paus, 2011, Paus and Arck, 2009, Peters et al., 2017). Therefore, it is important to highlight that, over the past decades, psychoneuroimmune research has revealed neuroendocrine-immune circuits that form a “brain-hair follicle (HF) axis” and well explain such a link (Arck, Slominski, et al., 2006; Peters et al., 2006). Evidence continues to accumulate that stress-induced hair growth inhibition and discoloration are more than figments of imagination but very real phenomena (Paus et al., 2006, Peters et al., 2017, Rosenberg et al., 2021). However, understanding the interaction between stress and hair health is complicated by the fact that hair loss in itself can be highly stressful and lead to significant psychological morbidity in affected individuals (Cash, 2001, de Koning et al., 1990, Hadshiew et al., 2004, Okhovat et al., 2019, Rencz et al., 2016, Titeca et al., 2020; Vélez-Muñiz et al., 2019). The observed hair loss in the context of COVID-19 has recently added a new perspective to this discussion and suggests a close bidirectional interaction between inflammatory strains and psychosocial stress (Olds et al., 2021, Peters et al., 2021).

In this review, we critically examine the evidence that perceived stress and/or key stress-associated neuroendocrine mediators can induce hair loss or premature hair greying. Mechanistically, we then examine how perceived stress and classical stress mediators are currently recognized to impact peripheral tissue physiology in mammals. This discussion reveals why the hair follicle (HF) is so superbly suited for experimentally dissecting the molecular and cellular key players of brain-body interactions (Peters et al., 2006). Subsequently we define important open questions and key areas of future investigation in this field. This includes the role of perceived stress-associated mediators such as cortisol that become deposited in the hair shaft (HS), and the potential role of altered microbiome and mitochondrial allostasis (Picard et al., 2014) in disrupting the hair cycle and/or hair pigmentation. Preclinical and clinical research models that are particularly well-suited to answer the most pressing open questions are briefly delineated before we close by suggesting specific therapeutic intervention strategies and targets to counteract the negative impact of perceived stress on hair growth and pigmentation.