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Background: Alopecia areata (AA) is a common cause of nonscarring hair loss that can have a profound psychological impact. Objectives: To assess the co‐occurrence of depression and anxiety in adults with AA compared with the general population, and to evaluate the mental health treatment burden and impact on time off work and unemployment. Methods: In total, 5435 people with newly diagnosed AA in UK primary care were identified from the Oxford Royal College of General Practitioners Research and Surveillance Centre network database, and matched to 21 740 controls. In cases and controls, we compared the prevalence and incidence of depressive episodes, recurrent depressive disorder and anxiety disorder, rates of time off work and unemployment, and, in those with pre‐existing mental health conditions, rates of mental health‐related prescribing and referral rates. This observational was registered with ClinicalTrials.gov (NCT04239521). Results: Depression and anxiety were more prevalent in people diagnosed with AA than in controls (P < 0·001). People with AA were also more likely to subsequently develop new‐onset depression and anxiety: adjusted hazard ratio (aHR) for recurrent depressive disorder 1·38 [95% confidence interval (CI) 1·13–1·69], depressive episodes aHR 1·30 (95% CI 1·04–1·62) and anxiety disorder aHR 1·33 (95% CI 1·09–1·63); to be issued time off work certificates (aHR 1·56, 95% CI 1·43–1·71); and to be recorded as unemployed (aHR 1·82, 95% CI 1·33–2·49). Higher rates of antidepressant prescribing were also seen in people with AA. Conclusions: People with AA have higher rates of depression and anxiety than those without AA. This impacts deleteriously on mental health treatment burden, time off work and unemployment. Evidence‐based mental health treatment programmes are needed for people with AA. [ABSTRACT FROM AUTHOR]

Importance: Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, ST3GAL1, and SEMA4B. However, CYP1B1, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A>G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies., Objective: To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in CYP1B1 (c.1358A>G, p.Asn453Ser) on FFA risk., Design, Setting, and Participants: This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023., Main Outcome and Measure: The main outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model., Results: Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34 254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31 177 (91.0%). An association between female FFA and the CYP1B1 risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; P = 8.41 × 10-8) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; P = .39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P = .02)., Conclusions and Relevance: This gene-environment interaction analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of CYP1B1 was associated with increased odds of FFA only in participants with OCP history.