Abstract
This case-control study uses data from the National Institutes of Health All of Us Research Program to investigate whether depression and anxiety are associated with lichen sclerosus among women.
Lichen sclerosus (LS) is a chronic inflammatory skin condition that primarily affects the anogenital area in women.1 Previous studies have shown that patients with LS experience increased psychological distress and decreased quality of life and have overall negative mental health outcomes.2,3,4,5 However, the risk of clinically diagnosed depression and anxiety in patients with LS is poorly understood. We investigated the association between LS, depression, and anxiety among adult women from the All of Us Research Program, a National Institutes of Health database providing clinical data on a socioeconomically diverse cohort of 214 206 US adults.6
Methods
This nested, matched, case-control study included US women aged 18 years or older recruited to the All of Us cohort from May 6, 2018, to February 11, 2022. The Yale University institutional review board deemed the study exempt from review because it was non–human participants research. We followed the STROBE reporting guideline.
We used electronic health record (EHR) data to identify LS, depression, and anxiety based on International Classification of Diseases, Ninth Revision, Clinical Modification; International Statistical Classification of Diseases, Tenth Revision, Clinical Modification; and/or SNOMED diagnostic codes (eMethods in the Supplement). Each case patient was matched to 4 control individuals based on age, sex, and race and ethnicity using nearest-neighbor propensity score matching with replacement. We used Pearson χ2 or Fisher exact tests for categorical variables and unpaired t tests for continuous variables to compare comorbidities between cases and controls. We used logistic regression to calculate odds ratios (ORs) and assess whether LS was associated with depression and anxiety. Multivariable models adjusted for age; race and ethnicity; smoking status; hypothyroidism and vitiligo, which are independently associated with LS; depression; and anxiety (eMethods in the Supplement). Data were analyzed using R, version 4.1.2. Two-sided P < .05 was considered significant.
Results
We identified 765 women with LS (mean [SD] age, 66.2 [12.5] years) and 3060 matched controls. Age and race and ethnicity were well matched between cases and controls. Women with LS were more likely to have a diagnosis of depression (325 [42.5%] vs 747 [24.4%]; P < .001) or anxiety (326 [42.6%] vs 693 [22.6%]; P < .001) compared with controls (Table 1). In multivariable analysis, LS remained significantly associated with depression (OR, 2.16; 95% CI, 1.82-2.57; P < .001) and anxiety (OR, 2.50; 95% CI, 2.10-2.97; P < .001) (Table 2).
Table 1. Clinical Characteristics of Patients With LS and Control Individuals Matched by Age, Sex, and Race and Ethnicity.
| Characteristic | Participants, No. (%)a | P value | |
|---|---|---|---|
| Matched controls (n = 3060) | Patients with LS (n = 765) | ||
| Age, mean (SD), y | 66.2 (12.5) | 66.2 (12.5) | .99 |
| Female | 3060 (100) | 765 (100) | >.99 |
| Race and ethnicity | |||
| Asian | 22 (0.7) | <20 (<2.6) | >.99 |
| Black | 188 (6.1) | 47 (6.1) | |
| Hispanic | 278 (9.1) | 69 (9.0) | |
| White | 2496 (81.6) | 624 (81.6) | |
| Otherb | 76 (2.5) | <20 (<2.6) | |
| Ever smoker | |||
| No | 1678 (54.8) | 473 (61.8) | .002 |
| Yes | 1254 (43.2) | 278 (36.3) | |
| Hypothyroidism | 540 (17.6) | 254 (33.2) | <.001 |
| Vitiligo | <20 (<0.7) | <20 (<2.6) | <.001 |
| Alcohol use disorder | 88 (2.9) | 21 (2.7) | .94 |
| Depression | 747 (24.4) | 325 (42.5) | <.001 |
| Anxiety | 693 (22.6) | 326 (42.6) | <.001 |
Abbreviation: LS, lichen sclerosus.
In accordance with the National Institutes of Health All of Us Research Program data and statistics dissemination policy, all values of fewer than 20 individuals are reported as such to protect the privacy of participants.
Race and ethnicity reported in the electronic health record as “other,” “more than 1,” or “unspecified.”
Table 2. Association of Lichen Sclerosus With Depression and Anxiety.
| Univariable analysis | Multivariable analysisa | |||
|---|---|---|---|---|
| Odds ratio (95% CI) | P value | Odds ratio (95% CI) | P value | |
| Depression | 2.29 (1.94-2.70) | <.001 | 2.16 (1.82-2.57) | <.001 |
| Anxiety | 2.54 (2.15-3.00) | <.001 | 2.50 (2.10-2.97) | <.001 |
Multivariable models adjusted for age, race and ethnicity, smoking status, hypothyroidism, and vitiligo.
Discussion
In this case-control study, LS was significantly associated with depression and anxiety among US women. Individuals with LS had a 2.16- and 2.5-fold increase in odds of receiving a diagnosis of comorbid depression or anxiety, respectively.
Few studies have examined associations between LS and depression or anxiety. In 1 cross-sectional survey study, 40% of 158 patients with LS showed signs of depression on a screening questionnaire; in another survey study of 26 patients with LS, 27% and 58% reported depression and anxiety, respectively.2,3 In a prospective survey study assessing quality of life in 68 patients with biopsy-proven vulvar LS, 19% had a history of anxiety and/or depression at baseline,4 and a retrospective study of 33 patients with LS found that 21% had comorbid depression or anxiety.5 Our data are consistent with these findings.
Limitations of this study include identification of LS, depression, and anxiety using EHRs; lack of clinical data on treatment, severity, or duration of LS; and inability to establish temporality between diagnoses of LS, depression, and anxiety. The study population also may not be generalizable to the entire US.
The association between LS and depression and anxiety may be attributable to its chronic nature and negative association with quality of life and sexual function.2,3,4,5 Health professionals treating patients with LS should recognize the increased risk of depression and anxiety, consider mental health screening, and refer patients with LS to mental health professionals when appropriate.
eMethods. Ascertainment of LS, Depression, and Anxiety
eReferences
References
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Associated Data
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Supplementary Materials
eMethods. Ascertainment of LS, Depression, and Anxiety
eReferences
