Alopecia Areata Is Associated with Posttraumatic Stress Disorder and Alcohol Use in a Case-Control Study of 4,785 Patients

Alopecia areata (AA) is a common autoimmune disorder characterized by nonscarring hair loss. There is inconsistency in the literature regarding the association between AA and psychiatric disease [1]. Additionally, few studies have evaluated potential association of AA with posttraumatic stress disorder (PTSD) and lifestyle factors, including alcohol use. We aimed to assess associations of AA with psychiatric disorders and lifestyle factors using a national database.

A nested case-control study using the National Institutes of Health All of Us database was conducted analyzing patients ≥18 years with AA diagnosis and controls matched 1:4 by age, sex at birth, and self-reported ethnicity/race. The following concept codes were used to identify AA and comorbidities: AA (concept code 141933, SNOMED 68225006), anxiety disorder (concept code 442077, SNOMED 197480006), depressive disorder (concept code 440383, SNOMED 35489007), PTSD (concept code 436676, SNOMED 47505003), obesity (concept code 433736, SNOMED 414916001), smoking frequency: every day (concept code 1585861), smoking frequency: some days (1585862), drink frequency past year: 2–4 per month (concept code 1586204), drink frequency past year: 2–3 per week (concept code 1586205), and drink frequency past year: 4 or more per week (concept code 1586206). Multivariate logistic regression was conducted to calculate odds ratios for AA and comorbidities. Positive history of smoking was designated as ≥100 cigarettes in lifetime. A separate case-control study assessing AA and medical comorbidities was conducted using the same patient cohort (under review).

There were 957 AA patients and 3,828 controls included in the final analysis. Mean age of AA patients was 55.8 years, 74.1% of patients were female, 40.8% of patients were white, 25.0% Hispanic or Latino, and 21.3% African American with similar age, sex, and race/ethnicity distribution for controls (all p = 1) (Table 1). AA patients had higher odds of depression (OR 1.36; 95% CI: 1.15–1.62; p < 0.001), PTSD (OR 1.73; 95% CI: 1.33–2.28; p < 0.001), anxiety (OR 1.36; 95% CI: 1.15–1.62; p < 0.001), and obesity (OR 1.21; 95% CI: 1.03–1.41; p = 0.01) (Table 2). AA patients had higher odds of having 2–4 drinks/month (OR 1.65; 95% CI; p < 0.001), 2–3 drinks/week (OR 1.56; 95% CI: 1.14–2.14; p = 0.04), and ≥4 drinks/week (OR 1.40; 95% CI: 0.99–1.98; p = 0.05). AA patients had lower odds of smoking some days (OR 0.50; 95% CI: 0.34–0.75; p < 0.001) and smoking everyday (OR 0.50; 95% CI: 0.38–0.67; p < 0.001).

We found that AA was associated with anxiety and depression, corroborating previous studies [1, 2]. In Okhovat et al.’s [1] meta-analysis of eight studies of AA patients, there was a positive association with anxiety (pooled OR 2.50; 95% CI: 1.54–4.06) and depression (pooled OR 2.71; 95% CI: 1.52–4.82). A population study of 41,055 AA patients and 41,055 controls by Tzur Bitan et al. [2] found that AA was associated with anxiety (OR 1.22; 95% CI: 1.13–1.31; p < 0.001) across all age groups above 30 years and with similar rates across genders. Depression was also associated with AA (OR 1.09; 95% CI: 1.01–1.17; p < 0.005), particularly in the 30–49 age group (OR 1.13; 95% CI: 1.03–1.26; p < 0.05) and in women (OR 1.15; 95% CI: 1.05–2.16; p < 0.01) [2]. Three studies in Okhovat et al.’s meta-analysis demonstrated no difference in mean anxiety [3‒5] and depression scores [4‒6] between AA patients and controls; however, the authors noted that these cohorts were younger and with less severe AA compared to AA cohorts in other studies [1].

The association between AA and depressive disorder may be bidirectional. In a population-based retrospective cohort study of 405,339 patients who developed major depressive disorder (MDD) and 5,378,596 patients who did not develop MDD, preexisting MDD was associated with increased risk of being diagnosed with AA (HR 1.90; 95% CI: 1.67–2.15; p < 0.001), and preexisting AA was associated with increased the risk of developing MDD (HR 1.34; 95% CI: 1.23–1.46; p < 0.001) [7]. Antidepressants had a protective effect on risk of developing AA (HR 0.57; 95% CI: 0.53–0.62; p < 0.001), indicating that treatment of depression may alter AA disease course [7].

Our study is the first case-control study to date reporting an association of AA with PTSD, which supports data from a cross-sectional national survey-based study of 1,449 AA patients, in which 33.9% of respondents screened positively for PTSD [8]. Total PTSD scores were higher in respondents who were younger (p < 0.001) and identified as African American versus white patients (p = 0.027), and Hispanic versus non-Hispanic patients (p = 0.002) [8]. These data support the hypothesis that psychological stress may play a role in autoimmune dysregulation in AA pathogenesis. Further studies evaluating temporal relation of PTSD and AA diagnoses are needed.

Our case-control study is the largest to date assessing association of AA with obesity. We found increased odds of obesity in AA patients, similar to Hagino et al.'s [9] survey-based study of 70 AA patients and 70 controls, which found that, on average, AA versus control patients had higher body mass index (OR 1.15; 95% CI: 1.02–1.29; p = 0.02). Importantly, these are associations and not necessarily causal relationships. It is possible that obesity enhances the cutaneous Th1 and/or Th2 immune response contributing to AA development [10]. Additionally, several recent studies have demonstrated a potential relation between AA and adiponectin and leptin, strengthening a possible association between obesity and AA [11, 12]. Higher odds of obesity in AA may also be potentially related to psychiatric comorbidities resulting in sedentary lifestyle.

We found that AA was associated with increased odds of alcohol use, but with decreased odds of smoking. A previous study utilizing the All of Us database demonstrated increased risk of alcohol use disorder diagnosis in AA patients [13]. Taken together, current evidence supports that AA patients may have a spectrum of alcohol use ranging from increased use to full-blown alcohol use disorder. Increased alcohol abuse among AA patients may be related to psychiatric comorbidities and AA-associated psychological distress. Further studies are needed to evaluate AA association with smoking, as well as the directional relationship of AA and alcohol use.

Limitations include inability to assess AA and psychiatric comorbidity severity. Temporal relation of psychiatric diagnoses/lifestyle factors with AA diagnosis was not evaluated.

In sum, our study strengthens previous associations of AA with anxiety, depression, PTSD, obesity, and alcohol use. Dermatologists may easily and efficiently assess for anxiety, depression, PTSD, and alcohol use disorder by administering the generalized anxiety disorder-2 (GAD-2), patient health questionnaire-2 (PHQ-2), primary care PTSD screen-5 (PC-PTSD-5), and alcohol use disorder identification test (AUDIT-C) scales, respectively, which are each two-five questions and in total take 2 minutes to complete. We recommend referral of AA patients to patient support groups and referral of those with positive psychiatric screenings to psychiatry.

We gratefully acknowledge all of us participants for their contributions, without whom this research would not have been possible. We also thank the National Institutes of Health’s All of Us Research Program for making available the participant data examined in this study.

Per the All of Us Research Hub at the National Institutes of Health: “as a single IRB, the All of Us IRB is charged with reviewing the protocol, informed consent, and other participant-facing materials for the All of Us Research Program. The IRB follows the regulations and guidance of the Office for Human Research Protections for all studies, ensuring that the rights and welfare of research participants are overseen and protected uniformly. The Researcher Workbench employs a data passport model, through which authorized users do not need IRB review for each research project. Most authorized users will not be conducting human subjects research with All of Us data for two reasons: (1) the research will not directly involve participants, only their data, and (2) the data available in the Researcher Workbench have been carefully checked and altered to remove identifying information while preserving their scientific utility.” This study protocol was reviewed and the need for informed consent was waived by Weill Cornell Medicine Institutional Review Board.

The authors have no conflicts of interest relevant to the content of this article.

The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276.

Kaya Curtis: prepared methodology, acquired and interpreted data for the work, wrote the original manuscript draft, prepared tables, gave final consent for the version to be published, and agreed to be accountable for all aspects of the work. Onajia Stubblefield: prepared methodology, acquired and interpreted data for the work, reviewed and edited the manuscript, gave final consent for the version to be published, and agreed to be accountable for all aspects of the work. Dr. Shari Lipner: conceptualized the work, prepared methodology, acquired and interpreted data for the work, reviewed and edited the manuscript, gave final consent for the version to be published, and agreed to be accountable for all aspects of the work.

The authors confirm that the data supporting the findings of this study are available within the article. Further inquiries can be directed to the corresponding author.