Accepted Manuscript

Association Between Alopecia Areata, Anxiety, and Depression: A Systematic Review

and Meta-analysis

Jean-Phillip Okhovat, MD, MPH, Dustin H. Marks, BS, Athena Manatis-Lornell, BA,
Dina Hagigeorges, BS, Joseph J. Locascio, PhD, Maryanne M. Senna, MD

PII: S0190-9622(19)30890-4
DOI: https://doi.org/10.1016/j.jaad.2019.05.086
Reference: YMJD 13507

To appear in: Journal of the American Academy of Dermatology

Received Date: 18 March 2019

Revised Date: 22 May 2019
Accepted Date: 30 May 2019

Please cite this article as: Okhovat J-P, Marks DH, Manatis-Lornell A, Hagigeorges D, Locascio JJ,
Senna MM, Association Between Alopecia Areata, Anxiety, and Depression: A Systematic Review and
Meta-analysis, Journal of the American Academy of Dermatology (2019), doi: https://doi.org/10.1016/
j.jaad.2019.05.086.

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Association Between Alopecia Areata, Anxiety, and Depression: A Systematic Review and
Meta-analysis

Jean-Phillip Okhovat, MD, MPH1, Dustin H. Marks, BS1, Athena Manatis-Lornell, BA1, Dina
Hagigeorges, BS1, Joseph J. Locascio, PhD2, Maryanne M. Senna, MD1,3
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Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.

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Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
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Harvard Medical School, Boston, MA

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Manuscript Word Count: 2,218 words
Capsule Summary Word Count: 36 words
Abstract Word Count: 196 words

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Number of References: 28
Number of Tables: 2
Number of Figures: 3

Funding Sources: None

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Conflicts of Interest: None to disclose

Corresponding author:
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Maryanne Makredes Senna, MD

Co-Director, MGH Hair Loss Clinic
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Director, Hair Academic Innovative Research (HAIR) Unit

Department of Dermatology
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Massachusetts General Hospital

50 Staniford St, Suite 200, Boston, MA 02115
msenna@partners.org
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Telephone: 617-726-2914
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Capsule Summary

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• Patients with alopecia areata (AA) may be at increased risk of anxiety and depression

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• Dermatologists and other healthcare providers should routinely assess for these

conditions among AA patients and refer patients to appropriate providers when indicated.

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Abstract

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Background: To date, there is no comprehensive meta-analysis analyzing the association

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between alopecia areata, anxiety, and depression.

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Objective: We sought to analyze the existing literature to examine the association between

alopecia areata, anxiety, and depression.

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Methods: We extracted literature from four databases including Medline, Embase, PsychINFO,

and Web of Science. We utilized the Preferred Reporting Items for Systematic Reviews and
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Meta-analyses (PRISMA) reporting guidelines in order to finalize a list of relevant articles to be

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included in our systematic review and meta-analysis. There were no restrictions placed on
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publication year or age of participants.

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Results: A total of 8 studies that included 6,010 patients with AA and 20,961 control patients

were included in the quantitative analysis. These included 4 cross-sectional studies and 4 case-
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control studies. Analysis of these studies demonstrated a positive association with anxiety
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(pooled OR, 2.50; 95% CI, 1.54-4.06) and depression (pooled OR, 2.71; 95% CI, 1.52-4.82).

Limitations: Publication bias may be a limitation of the study.

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Conclusion: This study suggests that patients with AA are at higher risk of both anxiety and

depression. Healthcare professionals must be cognizant of this higher risk and consider routine

assessment of these conditions and referral to appropriate providers when indicated.

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Introduction

Alopecia areata (AA) is an inflammatory, non-scarring form of hair loss that is believed to occur

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partly due to a loss of the immune privilege in the hair follicle, autoimmune-mediated hair

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follicle destruction, and upregulation of inflammatory pathways.1 Among the US population, it is

believed that the cumulative incidence of AA is 2%, with a prevalence of 0.1% to 0.2%.2-3

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Previous studies have sought to evaluate the prevalence of comorbid conditions among patients

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with AA. In a nationwide, population-based study including 4334 patients with alopecia areata
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identified from the National Health Insurance Database in Taiwan from 1996-2008, patients with

alopecia areata tended to have a significantly higher risk of associated vitiligo, lupus
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erythematosus, psoriasis, atopic dermatitis, thyroid disease, and allergic rhinitis.4

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Other studies have additionally sought to analyze the association between AA and psychiatric

disorders. In a case-control study including 5117 patients with AA and 20,468 age- and gender-
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matched controls, patients with AA were found to have an increased risk of depression in

patients aged < 20, and an increased rate of anxiety between the ages of 20 and 39.5 In another
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study by Huang et al (2014), among 3568 individuals with AA seen at tertiary care hospitals in
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Boston, MA during an 11-year period, mental health problems (such as depression or anxiety)

were found to be as high as 25.5%.6

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Other studies, however, have found no association between anxiety, depression, and alopecia

areata.7-10 We therefore sought to conduct a systematic review and meta-analysis of the available

literature to determine the association between psychiatric comorbidities, specifically anxiety

and depression, and alopecia areata.

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Materials and Methods

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Search Strategy and Study Inclusion

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We searched for articles in the following four databases: Medline, Embase, PsychINFO, and

Web of Science in accordance with the Preferred Reporting Items for Systematic Reviews and
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Meta-analyses (PRISMA) reporting guidelines to study the association between alopecia areata,
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anxiety, and depression.

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We included all English-language articles with no restrictions with regards to publication year or
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age of subjects. A total of 405 non-duplicate studies were identified. After screening titles and

abstracts, 348 articles were excluded and 57 were available for full-text review. Articles were
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only included for full-text review if they met inclusion criteria, which included a diagnosis of
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alopecia areata, a qualitative or quantitative assessment of anxiety or depression, and a

comparable control group. Of 57 articles available for full-text review, 40 articles were excluded

for one of the following reasons: no control group; only abstract available; wrong study design;

duplicate study; wrong patient population; data not extractable; or, no access to article. A total of
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9 articles were included in the qualitative analysis7-15 and 8 of these articles were included in the

quantitative analysis5, 16-22 for a total of 17 articles (Figure 1). We then categorized the articles

into 2 groups: those examining anxiety, and those examining depression.

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Data extraction

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Data extraction was performed by one reviewer (J.O.) and the following data was extracted from

each study included in the analysis: country of study; participant age (in years), sex; study

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design; assessment of alopecia areata; assessment of anxiety and/or depression; total number of
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individuals in study; anxiety and/or depression scores of study subjects, or prevalence of anxiety

and/or depression of study subjects. We additionally performed quality assessment using the
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Newcastle-Ottawa Scale (NOS) for observational studies.23 The NOS is a standardized method
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used to assess the quality of non-randomized studies, with a higher numerical value indicating a
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higher quality study.

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Meta-analyses
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A total of 8 studies were included in the anxiety meta-analysis and a separate depression meta-
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analysis. Studies that did not have a prevalence of anxiety or depression, but instead reported a

mean score of anxiety or depression, based on a variety of assessment tools, were only included

in the systematic review. For each meta-analysis, we calculated a pooled OR for anxiety and a
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separate pooled OR for depression based on the prevalence of each diagnosis in patients with a

diagnosis of AA and controls.

We utilized StatsDirect software (version 3, StatsDirect Ltd, Cheshire, UK) to calculate the odds

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ratios and 95% confidence intervals for the associations between AA, anxiety, and depression.

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We furthermore used random effects models by DerSimonian and Laird to obtain a pooled OR

and additionally examined for between-study heterogeneity by calculation of Cochrane Q

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statistic and I2 values. Publication bias was analyzed with visual inspection of funnel plots and

calculation of the Egger regression test to provide a quantitative assessment of publication bias.

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Results
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In this systematic review and meta-analysis, we included a total of 17 studies that compared
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levels of anxiety and depression among patients with AA. The studies were conducted in Europe
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(n=4), Asia (n=10), North America (n=2), and Africa (n=1). Twelve of the studies were cross-

sectional and five were case control. On a scale of 9 for case-control studies, NOS scores ranged
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from to 4 to 9; and, on a scale of 10 for cross-sectional studies, NOS scores ranged from 5 to 9,

indicating that most studies were of fair to good quality.

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Anxiety was assessed via a variety of tools, including the Minnesota Multiphasic Personality

Inventory, Symptom Checklist-90, Hamilton Rating Scale for Anxiety, State-Trait Anxiety

Inventories for Children, Spielberg’s Trait Anxiety Inventory, Taylor’s Manifest Anxiety Scale,
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Beck Anxiety Inventory, Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition,

Text Revision), Children’s Manifest Anxiety Scale, and Hospital Anxiety and Depression Scale.

Depression was similarly assessed via a variety of tools, including the Minnesota Multiphasic

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Personality Inventory, Symptom Checklist-90, Hamilton Rating Scale for Depression, Child

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Depression Inventory, Beck’s Depressive Inventory, Diagnostic and Statistical Manual of Mental

Disorders (Fourth Edition, Text Revision), and Hospital Anxiety and Depression Scale.

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AA, anxiety, and depression

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A total of 8 studies that included 6,010 patients with AA and 20,961 control patients were

included in the quantitative analysis. These included 4 cross-sectional studies and 4 case-control
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studies. Analysis of these studies demonstrated a positive association with anxiety (pooled OR,
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2.50; 95% CI, 1.54-4.06) and depression (pooled OR, 2.71; 95% CI, 1.52-4.82) (Figures 2 and
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3). A slightly asymmetrical funnel plot and a significant Egger regression test (p = 0.023),

however, indicated potential for publication bias among studies that assessed anxiety and among
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studies that assessed depression (p=0.003).

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In the qualitative analysis, a total of three studies demonstrated no significant difference in

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anxiety between AA patients and controls. One of these demonstrated that the mean SCL-90-R

subscale anxiety score of patients with AA was 0.74 +/- 0.62 and that of controls was 0.57 +/-

0.55 (p=0.07).7 Another study found that patients with AA did not have significantly different

state-anxiety scores or trait-anxiety scores compared to healthy siblings of AA patients.8 A third

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found that patients with AA did not have significantly different BAI scores compared to controls

(9.29 +/- 9.3 vs. 7.40 +/- 6.51, p >0.05).10 All six other studies in the qualitative analysis

demonstrated that patients with AA had significantly higher anxiety scores compared to control

patients.9,11-15

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Similarly, in the qualitative analysis, a total of three studies demonstrated no significant

difference in depression between AA patients and controls. One such study demonstrated that

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patients with AA did not have significantly different Children’s Depression Inventory scores

compared to healthy siblings of AA patients.8 Another such study demonstrated that children in

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the 9- through 11- year-old groups with AA did not differ from controls in symptoms depicting
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major depression.9 A third study demonstrated that patients with AA did not have significantly

different Beck Depression Inventory scores compared to controls.10 All four other studies in the
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qualitative analysis demonstrated that patients with AA had significantly higher depression
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scores compared to control patients.7,11,13-14

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As mentioned below, the studies that did not demonstrate a significant finding between AA,
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anxiety, and depression were among patients in younger age groups, or less severe disease.
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Discussion
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It is believed that stressful phenomena may lead to hair loss through a variety of mechanisms.

For instance, psychological stress triggers the hair follicle equivalent of the hypothalamic-

pituitary-adrenal (HPA) axis, resulting in increased corticotropic releasing hormone (CRH)

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secretion, which stimulates mast cell production and degranulation. This leads to neurogenic

inflammation that collapses the hair follicle immune privilege and induces premature destruction

of the follicle.24 Whether it is the actual psychiatric comorbidity that is associated with stress

(such as anxiety or depression) that leads to AA, or vice versa, however, is still poorly

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understood. Notably, however, our study confirms the findings of a recent population-based

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cohort study who were followed up for 26 years and registered with The Health Improvement

Network in general practices that included 405,339 patients who developed major depressive

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disorder and 5,738,596 patients who did not develop major depressive disorder. In this study,

major depressive disorder was found to increase the risk of subsequently developing AA by 90%

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(hazard ratio, 1.90; 95% CI, 1.67-2.15; P < .001), and AA was found to increase the risk of
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subsequently developing major depressive disorder by 34% (hazard ratio, 1.34; 95% CI, 1.23-

1.46; P < .001), after adjustment for covariates.25

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The four studies in the qualitative analysis that did not demonstrate a significant association
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between AA, anxiety, and depression were uniformly done in a younger age group or those with

less severe AA. Two studies that did not support a significant association between AA, anxiety,
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and depression were conducted in a pediatric population with mean ages of 12.2 and 10.5.8-9 with

most the cases (23/33) in one of these studies having patients with a disease duration of less than
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one year.9 In another study demonstrating no association between AA and anxiety in patients
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compared to controls, over a quarter of patients (28.8%) reported no scalp hair loss and 67.1% of

patient reported less than 25% scalp involvement.7 This is similar to a fourth study that found a

lack of association between AA and these psychiatric comorbidities where t84.6% of patients

(44/52) had < 25% hair loss.10 It is possible that pediatric patients may be less prone to
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developing depression and anxiety until they reach an older age when relations with their peers

become more significant. It is also plausible that patients with less severe AA could be at lower

risk of developing depression and anxiety because of their hair loss. Further studies are needed to

confirm these possibilities. These findings are in contrast to those hypothesized by Mulinari-

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Brenner who hypothesized that women, young patients, and those with significant AA or

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previous psychiatric disorders are at greater risk of psychiatric comorbidities.26

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This systematic review confirms other reports of higher rates of stress, anxiety, and depression

among patients with AA. Although not enough studies were published to date on risk of

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suicidality in AA patients to be included in this systematic review, some studies have looked at
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this risk in the AA population. Several studies have demonstrated that suicide attempts are

highest among patients with alopecia universalis (AU) and diffuse AA; for instance, one study
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demonstrated that suicidal ideation is reported in 60% of patients with AU, more than three times
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that reported in patients with localized alopecia (18%).27 Only one study in this systematic
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review assessed suicidality in patients with alopecia areata and demonstrated that patients with

AA were at an elevated risk of suicide and intentional self-inflicted injury (crude OR 2.84, 95%
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CI 1.78-4.55; adjusted OR 2.77, 95% CI 1.66-4.63).15 Further studies should be geared toward

assessing suicidal ideation and addressing these concerns in this patient population.
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It is important for clinicians to be mindful of psychiatric co-morbidities in AA patients such that

we can address patients holistically and refer them to appropriate groups and practitioners for

further support and treatment. Support groups, such as that offered by the National Alopecia

Areata Foundation (NAAF) provide people with a sense of normalization, acceptance, and
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understanding of their condition. Patients may often feel reassured when they see others who are

going through a similar experience and such individuals may be able to offer advice regarding

medical professionals or resources that have positively affected their lives.28

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The strengths of our meta-analysis include that we used a comprehensive search strategy, and

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there were multiple reviewers involved for both title/abstract screening and full-text screening to

resolve any possible discrepancies, including only studies that had a control (reference group),

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and including a variety of age ranges (including adolescents and adults). Limitations to our study

including lack of sub-analyses based on severity of alopecia and/or depression as all studies did

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not discuss the various degrees of psychiatric comorbidities. Furthermore, there is potential for
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publication bias as demonstrated by visual analysis of the Funnel plots and Egger test. However,

inclusion of the qualitative studies demonstrating lack of association may partially address this
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issue, particularly given some similarities in age of subjects and AA severity in these studies.
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Conclusions
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This systematic review and meta-analysis indicates that patients with AA are at an increased risk

of anxiety and depression. This seems to be particularly true for adult patients with more severe
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hair loss. The qualitative analysis did not demonstrate a significant association between AA,
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anxiety, and depression in younger patients or those with less severe AA, and further studies are

needed to better understand how psychiatric comorbidities in AA patients may be affected by

these factors. Dermatologists and other healthcare providers should be aware of the risk of

anxiety and depression in AA patients so that they may counsel patients appropriately and
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consider referral to appropriate specialists to adequately address psychiatric comorbidities when

indicated.

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Figure 1: PRISMA flow diagram demonstrating the selection process for study inclusion in the
systematic review and meta-analysis

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Figure 2: Forest Plot of the Effect Sizes between Alopecia Areata and Anxiety

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Figure 3: Forest Plot of the Effect Sizes between Alopecia Areata and Depression

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Table 1: Studies examining association between AA and anxiety

Reference Country Participant Sex, Study Assessment of Duration of Assessment of Total number Results
mean age in males/females: design alopecia disease in anxiety of individuals
years (SD) N (% female) areata months

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(SD)

Alfani et al Italy AA: 35.2 AA: 33/40 Cross- Clinical < 6 months: MMPI-2 146 total (73 Patients with AA had significantly

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(2012)* (9.2), (54.8%), sectional diagnosis by 36 (49.3%), AA and 73 higher scores of anxiety compared
Controls: 35.1 Controls: 33/40 clinician 6-11 Controls) to controls (p=0.001)
(9.1) (54.8%) months: 15

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(20.5%), >
12 months:
22 (30.1%)

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Annagur et al Turkey AA: 27.7 AA: 48/25 Cross- Clinical 23.25 (41.4) SCL-90-R 151 total (73 The mean score (SD) of patients
(2013) (7.8), (34.2%), sectional diagnosis by AA and 78 with AA was 0.74 +/- 0.62, and the

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Controls: 29.5 Controls: 44/34 clinician Controls) controls’ mean score (SD) was 0.57
(7.2) (43.6%) +/- 0.55 (p=0.07)
Ataseven et al Turkey AA: 23.4 AA: 31/12 Cross- Clinical 15.54 HAM-A 73 total (43 63% of patients with AA showed
(2011)* (11.4), (27.9%), sectional diagnosis by (36.37) AA and 30 anxiety, whereas only 23.3% of

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Controls: 26.7 Controls: 19/11 clinician Controls) controls showed anxiety (p<0.05)
(4.7) (36.7%)
Baghestani et Iran AA: 35.4 72% of both Case- Clinical Men: 22.7, HAM-A 136 total (68 The mean anxiety scale in the case

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al (2015)* (7.6), cases and control diagnosis by Women: AA and 68 group was significantly more than
Controls: 33.8 controls were clinician 20.8 Controls) that of the control group (12.76 +/-

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(8.1) male 7.21 vs 8.54 +/- 6.37; p=0.003)
Bilgic et al Turkey AA: 12.1 AA: 41/33 Cross- Clinical 13.5 (26.8) STAIc 139 total (74 Patients with AA had higher trait-
(2013) (2.8), (44.6%), sectional diagnosis by AA and 65 anxiety scores (36.3 +/- 6.9)
Controls: 12.3 Controls: 30/35 clinician Controls) compared to controls (34.0 +/- 5.4)
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(2.9) (53.8%) (p=0.028). Patients with AA had
higher state-anxiety scores (44.2 +/-
4.8) compared to controls (38.0 +/-
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8.4) (p<0.001)
Brajac et al Croatia AA: 40.0 AA: 17/28 Cross- Clinical Not given STAI 90 total (45 Patients with first onset of AA and
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(2003) (13.0), (62.2%), sectional diagnosis AA and 45 recidivism of AA had significantly

Controls: 40.0 Controls: 22/23 Controls) higher trait anxiety scores
(10.8) (51.1%) compared to controls (31.3 +/- 14.2
and 33.4 +/- 12.7 vs 21.1 +/- 11.2,
respectively)
Chu et al Taiwan AA and AA: 2517/2600 Case- AA defined Not given Anxiety 25,585 total Prevalence of anxiety in patients
(2011)* Controls, (50.8%), control according to defined (5117 AA and with AA (257, 5.0%) was
17.7% (0-19 Controls: ICD-9 code according to 20,468 significantly higher compared to
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years), 52.5% 10,068/10,400 704.01 ICD-9 codes Controls) controls (672, 3.3%) (p<0.01)
(20-39 years), (50.8%) 300.0-300.09
25.3% (40-59
years), 4.4%
(>60 years)

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Devar et al India 18-48 years All subjects Cross- Clinical Not given Taylor’s 60 total (30 Patients with AA had significantly
(1983) of age included in the sectional diagnosis by Manifest AA and 30 higher rates of anxiety (24.6 +/-
study were male clinician Anxiety Scale Controls) 10.9) compared to controls (16.4

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+/- 4.4) (p<0.01)
Diaz-Atienza Spain AA: 12.2 AA: 16/15 Cross- Clinical 3.2 years STAIc 56 total (31 Patients with AA did not have
et al (2011) (3.8), (48.4%), Healthy sectional diagnosis by (2.6 years) AA and 25 significantly different state-anxiety

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Healthy siblings of AA clinician Controls) scores compared to healthy siblings
siblings of patients: 14/11 of AA patients (8.9 +/- 6.8 vs. 10.0
AA patients: (44%) +/- 5.6, respectively. Patients with
12.4 (4.4) AA did not have significantly

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different trait-anxiety scores
compared to healthy siblings of AA

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patients (12.2 +/- 6.9 vs. 15.0 +/-
7.5, respectively).
Tulin Gulec et Turkey AA: 31.5 AA: 34/18 Case- Clinical 8.6 (14.1) Beck anxiety 104 total (52 Patients with AA did not have

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al (2004) (12.6), (34.6%), control diagnosis by inventory AA and 52 significantly different BAI scores
Controls: 31.9 Controls: 36/16 clinician Controls) compared to controls (9.29 +/- 9.3
(12.3) (30.8%) vs. 7.40 +/- 6.51) (p>0.05)

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Karia et al India AA: 27.8, AA: 33/17 Cross- Clinical 2.67 years Diagnostic and 100 total (50 The prevalence of anxiety was the
(2015)* Controls: 32.8 (34%), Controls: sectional diagnosis by (range 1-12 Statistical AA and 50 same among patients with AA and

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14/36 (72%) clinician years) Manual of Controls) controls (2 patients, 4%)
Mental
Disorders
Fourth Edition,
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Text Revision
Liakopoulou et Greece AA: 10.5 AA: 10/23 Cross- Clinical 23 children CMAS 63 total (33 Mean scores for four of five factors
al (1996) (0.3), (69.7%), sectional diagnosis by with AA and 30 of the CMAS were significantly
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Controls: 10.6 Controls: 11/19 clinician duration < 1 Controls) higher in AA patients compared to
(1.9) (63.3%) year, 10 controls
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with
duration 1-3
years
Miller et al United AA: 35.5 AA: 184/400 Case- Electronic Not given Not given 756 total (584 The OR of having anxiety was not
(2015)* States (19.3), (68.5%), control medical AA and 172 significantly different among
Controls: 35.8 Controls: 46/126 records Controls) patients with AA and controls
(15.6) (73.3%) (1.45, 0.83-2.52), p=0.1882
Sahiner et al Turkey AA: 32.9 AA: 49% Cross- Clinical < 3 months: Beck Anxiety 91 total (41 Mean BAI score was significantly
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(2014)* (10.5), male/51% sectional diagnosis by 16 (39%); Inventory AA and 50 different among AA patients and
Controls: 35 female, Controls: clinician 3-12 Controls) controls (12.8 +/- 12.9 vs. 5.0 +/-
(13.8) 42% male/58% months: 12 4.7, respectively, p<0.05)
female (29.3%);
12-24

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months: 1
(2.4%); 2-5
years: 6

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(14.6%); >
5 years: 6
(14.6%)

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Sayar et al Turkey AA: 23.8 All subjects in Cross- Clinical Not given State-Trait 71 total (31 Patients with AA had significantly
(2001) (2.5), the study and the sectional diagnosis by Anxiety AA and 40 higher state-anxiety scores
Controls: 22.7 control group clinician Inventory Controls) compared to controls (46.0 +/- 10.7
(2.3) were males vs. 39.5 +/- 5.2) (p<0.01). Patients

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with AA had significantly higher
trait-anxiety scores compared to

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controls (51.5 +/- 9.0 vs. 47.0 +/-
6.5 (p<0.05).
Sellami et al Tunisia AA: 32.9 AA: 48% Case- Clinical Mean HADS Not given Patients with AA had significantly

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(2013)* (11.8) male/52% female control diagnosis by duration of higher scores of anxiety (10.4 +/-
clinician hair loss 3.5) compared to controls (7.9 +/-
prior to 3.48) (p=0.005)

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diagnosis:
69.28 days

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(range 1-
400 days)
Singam et al United Not given Not given Cross- AA was Not given Mental health 11978648 total Patients with AA had a higher
(2018) States sectional identified by co-morbidities (366 with AA, crude OR (2.34, 1.84-2.96) and
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ICD-9-CM were 11978282 adjusted OR (2.46, 1.91-3.16) of
code 704.01 determined by patients anxiety disorders compared to
Clinical without AA) patients without AA (p<0.0001)
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Classification
Software codes
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650-663 and
670
*Included in meta-analysis
MMPI-2: Minnesota Multiphasic Personality Inventory-2 STAIc: State-Trait Anxiety Inventories for Children
SALT: Severity of Alopecia Tool STAI: Spielberg’s Trait Anxiety Inventory
SCL-90-R: Symptom Checklist-90 CMAS: Children’s Manifest Anxiety Scale
HAM-A: Hamilton Rating Scale for Anxiety HADS: Hospital Anxiety and Depression Scale
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2 Table 2: Studies examining association between AA and depression

Reference Country Participant Sex, Study Assessment of Duration of Assessment of Total number Results
mean age in males/females: design alopecia disease in depression of individuals
years (SD) N (% female) areata months (SD)

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Alfani et al Italy AA: 35.2 AA: 33/40 Cross- Clinical < 6 months: 36 MMPI-2 146 total (73 Patients with AA had
(2012)* (9.2), (54.8%), sectional diagnosis by (49.3%), 6-11 AA and 73 significantly higher scores of
Controls: 35.1 Controls: 33/40 clinician months: 15 Controls) depression compared to

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(9.1) (54.8%) (20.5%), > 12 controls (p=0.003)
months: 22
(30.1%)

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Annagur et al Turkey AA: 27.7 AA: 48/25 Cross- Clinical 23.25 (41.4) SCL-90-R 151 total (73 The mean depression score
(2013) (7.8), (34.2%), sectional diagnosis by AA and 78 for AA patients was
Controls: 29.5 Controls: 44/34 clinician Controls) significantly higher
(7.2) (43.6%) compared to controls (1.02

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+/- 0.72 vs. 0.73 +/- 0.56,

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p=0.01)
Ataseven et al Turkey AA: 23.4 AA: 31/12 Cross- Clinical 15.54 (36.37) HAM-D 73 total (43 50% of AA patients had
(2011)* (11.4), (27.9%), sectional diagnosis by AA and 30 either mild, moderate, or
Controls: 26.7 Controls: 19/11 clinician Controls) severe depression, whereas

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(4.7) (36.7%) only 30% of controls showed
depression (p<0.05)
Baghestani et Iran AA: 35.4 72% of both Case- Clinical Men: 22.7, HAM-D 136 total (68 The mean depression scale in

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al (2015)* (7.6), cases and control diagnosis by Women: 20.8 AA and 68 the case group was
Controls: 33.8 controls were clinician Controls) significantly more than that

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(8.1) male of the control group (12.84
+/- 4.03 vs 6.22 +/- 1.95;
p=0.003)
Bilgic et al Turkey AA: 12.1 AA: 41/33 Cross- Clinical 13.5 (26.8) CDI 139 total (74 Patients with AA
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(2013) (2.8), (44.6%), sectional diagnosis by AA and 65 significantly higher
Controls: 12.3 Controls: 30/35 clinician Controls) depression scores (10.4 +/-
(2.9) (53.8%) 6.9) compared to controls
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(8.2 +/- 6.1) (p=0.036)

Chu et al Taiwan AA and AA: 2517/2600 Case- AA defined Not given Major 25,585 total Prevalence of depression in
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(2011)* Controls: (50.8%), control according to depressive (5117 AA and patients with AA (146,
17.7% (0-19 Controls: ICD-9 code disorder 20,468 2.9%) was significantly

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years), 52.5% 10,068/10,400 704.01 defined Controls) higher compared to controls

(20-39 years), (50.8%) according to (444, 2.2%) (p<0.01)
25.3% (40-59 ICD-9 codes
years), 4.4% 296.0-296.16
(>60 years)
Devar et al India 18-48 years of All subjects Cross- Clinical Not given Beck’s 60 total (30 Patients with AA had
(1983) age included in the sectional diagnosis by Depressive AA and 30 significantly higher rates of

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study were male clinician Inventory Controls) depression (20.5 +/- 13.1)
compared to controls (2.2 +/-
2.0) (p<0.001)

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Diaz-Atienza Spain AA: 12.2 AA: 16/15 Cross- Clinical 3.2 years (2.6 Children’s 56 total (31 Patients with AA did not
et al (2011) (3.8), Healthy (48.4%), Healthy sectional diagnosis by years) Depression AA and 25 have significantly different
siblings of AA siblings of AA clinician Inventory Controls) depression scores compared

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patients: 12.4 patients: 14/11 to healthy siblings of AA
(4.4) (44%) patients (9.8 +/- 5.3 vs. 9.7
+/- 4.7, respectively)
Tulin Gulec et Turkey AA: 31.5 AA: 34/18 Case- Clinical 8.6 (14.1) Beck 104 total (52 Patients with AA did not

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al (2004) (12.6), (34.6%), control diagnosis by depression AA and 52 have significantly different
Controls: 31.9 Controls: 36/16 clinician inventory Controls) BDI scores compared to

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(12.3) (30.8%) controls (11.52 +/- 9.1 vs.
9.17 +/- 6.85) (p>0.05)
Karia et al India AA: 27.8, AA: 33/17 Cross- Clinical 2.67 years Diagnostic and 100 total (50 The prevalence of depression

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(2015)* Controls: 32.8 (34%), Controls: sectional diagnosis by (range 1-12 Statistical AA and 50 was higher among patients
14/36 (72%) clinician years) Manual of Controls) with AA than controls (9,
Mental 18% in AA patients vs. 0 in

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Disorders controls)
Fourth Edition,

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Text Revision
Liakopoulou Greece AA: 10.5 AA: 10/23 Cross- Clinical 23 children Children’s 63 total (33 Children in the 9- through
et al (1996) (0.3), (69.7%), sectional diagnosis by with duration < Depression AA and 30 11-year-old groups with AA
Controls: 10.6 Controls: 11/19 clinician 1 year, 10 with Inventory Controls) did not differ from controls
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(1.9) (63.3%) duration 1-3 in symptoms depicting major
years depression. Mean values for
subjects with AA were 9.4
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+/- 7.5 and for controls 6.8

+/- 4.5 (p=0.26)
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Miller et al United AA: 35.5 AA: 184/400 Case- Electronic Not given Not given 756 total (584 The OR of having depression
(2015)* States (19.3), (68.5%), control medical AA and 172 was not significantly
Controls: 35.8 Controls: 46/126 records Controls) different among patients with
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(15.6) (73.3%) AA and controls (1.41, 0.84-

2.41), p=0.1928
Sahiner et al Turkey AA: 32.9 AA: 49% Cross- Clinical < 3 months: 16 Beck 91 total (41 Mean BDI score was
(2014)* (10.5), male/51% sectional diagnosis by (39%); 3-12 Depression AA and 50 significantly different among
Controls: 35 female, clinician months: 12 Inventory Controls) AA patients and controls
(13.8) Controls: 42% (29.3%); 12-24 (13.2 +/- 10.9 vs. 4.9 +/- 3.8,
male/58% months: 1 respectively, p<0.05)

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female (2.4%); 2-5
years: 6
(14.6%); > 5

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years: 6
(14.6%)
Sayar et al Turkey AA: 23.8 All subjects in Cross- Clinical Not given Beck 71 total (31 Patients with AA had

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(2001) (2.5), the study and the sectional diagnosis by Depression AA and 40 significantly higher
Controls: 22.7 control group clinician Inventory Controls) depression scores compared
(2.3) were males to controls (21.0 +/- 10.2 vs.
15.2 +/- 8.5, p<0.05)

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Sellami et al Tunisia AA: 32.9 AA: 48% Case- Clinical Mean duration HADS Not given Patients with AA had
(2013)* (11.8) male/52% control diagnosis by of hair loss significantly higher scores of

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female clinician prior to depression (8.96 +/- 4.43)
diagnosis: compared to controls (7.18
69.28 days +/- 3.72) (p=0.047)

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(range 1-400
days)
3 *Included in meta-analysis

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4 MMPI-2: Minnesota Multiphasic Personality Inventory-2
5 SALT: Severity of Alopecia Tool

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6 SCL-90-R: Symptom Checklist-90
7 HAM-D: Hamilton Rating Scale for Depression
8 CDI: Child Depression Inventory
9 HADS: Hospital Anxiety and Depression Scale
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15 Acknowledgment:
16
17 We are indebted to Ms. Lisa Liang Philpotts for her assistance with developing and validating our study search
18 strategy.
19
20
21 References:
22

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27 Arch Dermatol, 128 (1992), p. 702
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