Postpartum Depression Risk in Hidradenitis Suppurativa: A Matched Cohort Study and Case–Control Analysis

Postpartum Depression Risk in Hidradenitis Suppurativa: A Matched Cohort Study and Case–Control Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Postpartum Depression Risk in Hidradenitis Suppurativa: A Matched Cohort Study and Case–Control Analysis Dorsa Moslehi, Monika Bapna, Frederick Gibson, Natalie Feldman, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8981781/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Introduction Hidradenitis suppurativa (HS) disproportionately affects women of reproductive age and is associated with psychiatric comorbidity, but its relationship with postpartum depression (PPD) is unclear. We conducted two complementary studies to assess PPD risk in HS and associated factors among postpartum patients with HS. Methods Part A : TriNetX EHR data (2005–2023) were used to identify postpartum females aged 18–45 years. Patients with pre-delivery HS were compared with those without HS. PPD was defined by ICD-10 codes (F53.0, F32.0–F32.3) within 365 days postpartum, excluding MDD in the 12 months pre-pregnancy. Cohorts were propensity score–matched 1:1 on demographics, psychiatric history, and comorbidities. Part B : In the Mass General Brigham Research Patient Data Registry, we conducted an age-matched case–control study among postpartum females aged 18–45 years with dermatologist-confirmed HS. Cases had PPD within 1 year postpartum; controls had no PPD. Demographic, psychiatric/substance use, obstetric, and HS-related factors were compared using univariable tests. Results Part A : PPD occurred in 4.9% of patients with HS versus 2.1% without HS (RR 2.31; 95% CI, 2.10–2.54; P<.0001). The association persisted after matching for age and race/ethnicity (RR 2.15; 95% CI, 1.82–2.55; P<.0001) and after additional adjustment for psychiatric comorbidities and obstetric complications (RR 1.32; 95% CI, 1.14–1.52; P=.0002). New antidepressant/anxiolytic prescriptions were higher in HS (RR 1.44; 95% CI, 1.28–1.62; P<.0001). Part B : Among 46 cases and 37 controls (95 vs 67 deliveries), race/ethnicity differed (cases more often White, less often Asian; χ² P=.0075). Prior depression (P=.0396) and trauma- or stressor-related disorders (P=.0190) were more common in cases along with peripartum complications (63.2% vs 26.9%; P<.0001), and higher BMI at delivery (P=.0012). Cases were younger at first clinician-documented HS diagnosis (P=.0001) and less often reported HS symptoms preceding diagnosis (P=.0207). No differences were observed in Hurley stage, HS-related utilization, or treatment exposure. Conclusions HS may represent a postpartum window of heightened depression risk, with increased PPD incidence after adjustment for confounders. Peripartum complications, higher BMI, and psychiatric history may identify highest-risk patients. Prospective studies are needed to confirm predictors and inform screening. Hidradenitis suppurativa postpartum depression perinatal mental health pregnancy Introduction Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that disproportionately affects women of reproductive age [ 1 , 2 ]. Patients with HS experience a high burden of psychiatric comorbidity, including major depressive disorder (MDD) and anxiety disorders [ 3 ]. Despite this elevated baseline risk, the relationship between HS and postpartum depression (PPD) has not been well-characterized. We conducted 2 complimentary studies: (1) a retrospective cohort study evaluating PPD risk among women with HS compared with those without HS, and (2) a case–control study assessing risk factors for PPD among women with HS. Methods Study A: Retrospective Cohort Study TriNetX Research Network, a federated, de-identified electronic health record database was used. Female patients aged 18–45 years with a documented live birth between January 1, 2005, and December 31, 2023, were eligible. Exposure cohort included patients with a diagnosis of HS prior to delivery; comparators had no documented HS diagnosis. PPD was defined using ICD-10 codes for postpartum-onset depressive disorders (F53.0) and MDD (F32.0–F32.3) recorded within 365 days following delivery. Patients with MDD documented during the 12 months preceding pregnancy were excluded. All patients were required to have at least 12 months of observable follow-up after delivery. Exposure and comparator cohorts were propensity score–matched 1:1 on age at delivery, race and ethnicity, psychiatric history, and selected medical comorbidities. Psychiatric history was included as a binary covariate, defined as the presence of any documented ICD-10 psychiatric diagnosis prior to the index pregnancy (yes/no), rather than individual psychiatric disorders or severity categories. Propensity score matching was performed using nearest-neighbor matching without replacement. Study B: Case–Control Study Data from the Mass General Brigham (MGB) Research Patient Data Registry (RPDR) was used. Female patients aged 18–45 years with HS and ≥ 1 live birth were eligible. Cases had HS (identified using ICD codes in Part A and confirmed by dermatologist documentation) and PPD diagnosed within 1 year postpartum using ICD codes in Part A. Controls were patients with HS and ≥ 1 delivery but no PPD diagnosis, age-matched to cases. Only live births with sufficient HS and obstetric documentation were included. The final cohort included 46 cases and 37 controls, contributing 95 and 67 eligible deliveries, respectively; patients could contribute > 1 delivery. Demographic, psychiatric, obstetric, and HS clinical characteristics were abstracted from the medical record, with HS severity and treatment exposure assessed cumulatively up to each eligible delivery. Continuous, binary, and categorical variables were compared using independent-samples t-tests, z-tests for proportions, or chi-square tests, as appropriate, with Welch’s correction applied when indicated. Statistical significance was defined as a two-sided P < .05, with Bonferroni-adjusted thresholds explored in sensitivity analyses. Multivariable modeling was not performed due to limited sample size. The MGB IRB deemed the study exempt. Results Part A: Retrospective Cohort Study PPD occurred in 4.9% of females with HS and 2.1% without HS (risk ratio [RR], 2.31; 95% CI, 2.10–2.54; P < .0001) (Table 1). After matching for age at childbirth and race and ethnicity, PPD remained more common among females with HS (4.9% vs 2.28%; RR, 2.15; 95% CI, 1.82–2.55; P < .0001). Additional matching for psychiatric comorbidities attenuated but did not eliminate the association between HS and PPD (RR, 1.35; 95% CI, 1.17–1.56; P < .0001). In a separately propensity score–matched cohort that additionally included obstetric complications, HS remained associated with higher PPD incidence (RR, 1.32; 95% CI, 1.14–1.52; P = .0002). Among patients without prior antidepressant or anxiolytic use, new prescriptions for these medications were more common in patients with HS than in those without HS (11.5% vs 8.0%; RR, 1.44; 95% CI, 1.28–1.62; P < .0001). Among patients with HS, PPD incidence did not differ by biologic treatment exposure (RR, 0.83; 95% CI, 0.49–1.40; P = .48). Part B: Case–Control Study Demographic characteristics Race and ethnicity differed between HS patients with and without PPD (χ² P = .0075), with patients with PPD more frequently White and less frequently Asian ( Table 2, Supplementary Table S3 ). No differences were observed by income source, insurance, employment or caregiving status (single parent, co-parenting, or no custody of children). Psychiatric and substance use history Prior depression (P = .0396) and trauma- or stressor-related disorders (P = .0190) were more common among patients with PPD.( Table 2, Supplementary Table S2 ). Substance use history was more common among patients without PPD (P = .0278), while smoking history did not differ. Obstetric characteristics Peripartum complications, including hypertensive disorders of pregnancy, infection, postpartum hemorrhage, genital tract injury, and breastfeeding-related complications, were more frequent among women with postpartum depression (63.2% vs 26.9%; P < .0001) ( Table 2, Supplementary Table S2 ). Body mass index (BMI) at delivery was also higher among women with postpartum depression (P = .0012) ( Table 2, Supplementary Table S1 ). No significant differences were observed for gravidity, parity, planned pregnancy, preterm birth, intrapartum complications, or neonatal intensive care unit admission. HS-related characteristics Patients with PPD were younger at first clinician-documented HS diagnosis (P = .0001), and patient-reported HS symptoms or diagnosis preceding clinician documentation were less common (P = .0207) ( Table 2, Supplementary Table S3 ). No differences were observed in Hurley stage at diagnosis or delivery, HS-related healthcare utilization, or HS treatment exposure. Discussion PPD occurs more frequently among patients with HS than among patients without HS, even after accounting for demographic, psychiatric, and obstetric factors. While HS is well recognized to be associated with an increased burden of depression and anxiety, these findings extend that association specifically to the postpartum period (PPP), identifying this interval as a distinct window of vulnerability [ 4 – 6 ]. HS frequently flares in the PPP which may increase the physiologic and psychosocial demands of the already demanding PPP [ 2 , 7 ]. In addition, systemic inflammation associated with HS, including elevated levels of TNF–α, has been implicated in perinatal mood disorders, suggesting a potential shared inflammatory pathway linking HS and PPD [ 8 , 9 ]. The case–control analysis examined whether specific demographic, psychiatric, obstetric, or HS-related characteristics differed between patients with HS with and without PPD. After adjustment for multiple comparisons, peripartum complications and higher BMI at delivery were most strongly associated with PPD, suggesting that increased physiologic burden during pregnancy may contribute to elevated PPD risk among patients with HS. Markers of HS severity, including Hurley stage, treatment exposure, and HS-related hospitalizations, did not differ between groups, consistent with prior studies showing that depression and anxiety risk in HS is not strongly correlated with disease severity [ 10 ]. This study has several limitations. Both analyses were retrospective and relied on electronic health record data, which may be subject to misclassification and residual confounding. Postpartum depression was identified using diagnostic codes rather than standardized screening instruments, which may underestimate prevalence. In the retrospective cohort, patients with major depressive disorder prior to pregnancy were excluded to isolate incident PPD; however, this excluded a high-risk subgroup, potentially limiting generalizability and underestimating overall PPD burden among women with HS. The case–control analysis was limited by sample size and incomplete longitudinal capture of HS disease activity, precluding multivariable modeling and limiting power to detect modest associations. These findings are hypothesis-generating and require confirmation in prospective studies. If confirmed, women with HS may represent a population warranting closer PPD screening and support. Declarations Funding : None Sources of support that require acknowledgment : None Authors’ financial disclosures and conflicts of interest : None Data availability statement : The data underlying this article cannot be shared publicly due to privacy and ethical restrictions. De-identified patient-level data are available from the Mass General Brigham Research Patient Data Registry upon reasonable request and with appropriate institutional approvals. References Chellappan B, Nguyen DDQ, Hoyer P et al (2022) Dermatologic Management of Hidradenitis Suppurativa and Impact on Pregnancy and Breastfeeding. Cutis 109:160–162 Seivright JR, Villa NM, Grogan T et al (2022) Impact of Pregnancy on Hidradenitis Suppurativa Disease Course: A Systematic Review and Meta-Analysis. Dermatol Basel Switz 238:260–266 Holgersen N, Rosenø NAL, Nielsen VW et al (2025) Risk of New-Onset and Recurrent Depression and Anxiety Among Patients With Hidradenitis Suppurativa. JAMA Dermatol 161:1014–1021 Cohn E, Palma G, Mastacouris N et al (2024) Incidence of anxiety disorder in adults with hidradenitis suppurativa. Br J Dermatol 191:351–356 Wright S, Strunk A, Garg A (2020) New-onset depression among children, adolescents, and adults with hidradenitis suppurativa. J Am Acad Dermatol 83:1360–1366 Wright S, Strunk A, Garg A (2022) Prevalence of depression among children, adolescents, and adults with hidradenitis suppurativa. J Am Acad Dermatol 86:55–60 Đurinec P, Bukvić Mokos Z, Marinović B (2025) The psychosocial effects of hidradenitis suppurativa. Clin Dermatol 43:462–470 Leboit PE, Patel DU, Cohen JN et al (2025) The Inflammatory Landscape of a Whole-Tissue Explant Model of Hidradenitis Suppurativa. Exp Dermatol 34:e70057 Silva-Fernandes A, Conde A, Marques M et al (2024) Inflammatory biomarkers and perinatal depression: A systematic review. PLoS ONE 19:e0280612 Holgersen N, Rosenø NAL, Nielsen VW et al (2025) Risk of New-Onset and Recurrent Depression and Anxiety Among Patients With Hidradenitis Suppurativa. JAMA Dermatol 161:1014–1021 Tables Table 1 to 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files HSPPDtables.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 05 May, 2026 Editor assigned by journal 28 Feb, 2026 Submission checks completed at journal 28 Feb, 2026 First submitted to journal 26 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8981781","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":636774286,"identity":"2fc0e293-c9af-484f-b9ee-b1f92e222583","order_by":0,"name":"Dorsa Moslehi","email":"","orcid":"","institution":"Harvard Medical School","correspondingAuthor":false,"prefix":"","firstName":"Dorsa","middleName":"","lastName":"Moslehi","suffix":""},{"id":636774287,"identity":"31dff547-26b9-41ce-bcb9-8a4c7408435d","order_by":1,"name":"Monika Bapna","email":"","orcid":"","institution":"Georgetown School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Monika","middleName":"","lastName":"Bapna","suffix":""},{"id":636774288,"identity":"89384c1a-b3ed-4a4a-aab0-582210adf74d","order_by":2,"name":"Frederick Gibson","email":"","orcid":"","institution":"Harvard Medical School","correspondingAuthor":false,"prefix":"","firstName":"Frederick","middleName":"","lastName":"Gibson","suffix":""},{"id":636774289,"identity":"bcf6d499-0a9e-4a49-be02-d2fb4d983464","order_by":3,"name":"Natalie Feldman","email":"","orcid":"","institution":"Harvard Medical School","correspondingAuthor":false,"prefix":"","firstName":"Natalie","middleName":"","lastName":"Feldman","suffix":""},{"id":636774290,"identity":"61dc27d6-d40e-4535-b7ee-60f6a32a68cd","order_by":4,"name":"Stephanie R. Cohen","email":"","orcid":"","institution":"Harvard Medical School","correspondingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"R.","lastName":"Cohen","suffix":""},{"id":636774291,"identity":"ef416f14-f58c-459e-b776-a93943e73b1c","order_by":5,"name":"Alexandra P. Charrow","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYFACHgjFL8HAxsDYAOFIMDAwE9YiOYNkLQY3iNXC33724OfKPTaJm2/3mD1g3GGXb3D87MMbDBXWiQ04tEicyUuWPPMsLXHbnTPmBoxnki03nEk3tmA4k45TC8MNHgPJhgOHc7fdyN0mwdjGDOSlsQEZh3Fqkb/BY/wTpGXzDLCWegPJ/mdALf9wazG4wWMGtmWDBFjLYQN+CZAtDbi1GJ7JMbNsOJBWP+PO+W8SiW3HgVqeMVskHEs3xqVF7vgZ45sNB2yM+We3pUl8bKs2YONPY7zxocZaFqf3UUACBmMUjIJRMApGAVkAAFYfWcyDXEWTAAAAAElFTkSuQmCC","orcid":"","institution":"Harvard Medical School","correspondingAuthor":true,"prefix":"","firstName":"Alexandra","middleName":"P.","lastName":"Charrow","suffix":""}],"badges":[],"createdAt":"2026-02-26 22:23:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8981781/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8981781/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109249584,"identity":"586a1df8-dad7-40e2-aa13-97007eafc197","added_by":"auto","created_at":"2026-05-14 08:56:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":112255,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8981781/v1/f7fd4016-77d8-4eaf-b9bf-07984cf56e37.pdf"},{"id":109159066,"identity":"8b9364c6-b204-4bb6-af11-14316f0e3e63","added_by":"auto","created_at":"2026-05-13 07:22:48","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":29209,"visible":true,"origin":"","legend":"","description":"","filename":"HSPPDtables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8981781/v1/b902eab22d94e61cbb29aab4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Postpartum Depression Risk in Hidradenitis Suppurativa: A Matched Cohort Study and Case–Control Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that disproportionately affects women of reproductive age [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Patients with HS experience a high burden of psychiatric comorbidity, including major depressive disorder (MDD) and anxiety disorders [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Despite this elevated baseline risk, the relationship between HS and postpartum depression (PPD) has not been well-characterized.\u003c/p\u003e \u003cp\u003eWe conducted 2 complimentary studies: (1) a retrospective cohort study evaluating PPD risk among women with HS compared with those without HS, and (2) a case\u0026ndash;control study assessing risk factors for PPD among women with HS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy A: Retrospective Cohort Study\u003c/h2\u003e \u003cp\u003eTriNetX Research Network, a federated, de-identified electronic health record database was used. Female patients aged 18\u0026ndash;45 years with a documented live birth between January 1, 2005, and December 31, 2023, were eligible. Exposure cohort included patients with a diagnosis of HS prior to delivery; comparators had no documented HS diagnosis.\u003c/p\u003e \u003cp\u003ePPD was defined using ICD-10 codes for postpartum-onset depressive disorders (F53.0) and MDD (F32.0\u0026ndash;F32.3) recorded within 365 days following delivery. Patients with MDD documented during the 12 months preceding pregnancy were excluded. All patients were required to have at least 12 months of observable follow-up after delivery.\u003c/p\u003e \u003cp\u003eExposure and comparator cohorts were propensity score\u0026ndash;matched 1:1 on age at delivery, race and ethnicity, psychiatric history, and selected medical comorbidities. Psychiatric history was included as a binary covariate, defined as the presence of any documented ICD-10 psychiatric diagnosis prior to the index pregnancy (yes/no), rather than individual psychiatric disorders or severity categories. Propensity score matching was performed using nearest-neighbor matching without replacement.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy B: Case–Control Study\u003c/h3\u003e\n\u003cp\u003eData from the Mass General Brigham (MGB) Research Patient Data Registry (RPDR) was used. Female patients aged 18\u0026ndash;45 years with HS and \u0026ge;\u0026thinsp;1 live birth were eligible. Cases had HS (identified using ICD codes in Part A and confirmed by dermatologist documentation) and PPD diagnosed within 1 year postpartum using ICD codes in Part A. Controls were patients with HS and \u0026ge;\u0026thinsp;1 delivery but no PPD diagnosis, age-matched to cases. Only live births with sufficient HS and obstetric documentation were included. The final cohort included 46 cases and 37 controls, contributing 95 and 67 eligible deliveries, respectively; patients could contribute\u0026thinsp;\u0026gt;\u0026thinsp;1 delivery.\u003c/p\u003e \u003cp\u003eDemographic, psychiatric, obstetric, and HS clinical characteristics were abstracted from the medical record, with HS severity and treatment exposure assessed cumulatively up to each eligible delivery.\u003c/p\u003e \u003cp\u003eContinuous, binary, and categorical variables were compared using independent-samples t-tests, z-tests for proportions, or chi-square tests, as appropriate, with Welch\u0026rsquo;s correction applied when indicated. Statistical significance was defined as a two-sided P \u0026lt; .05, with Bonferroni-adjusted thresholds explored in sensitivity analyses. Multivariable modeling was not performed due to limited sample size. The MGB IRB deemed the study exempt.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePart A: Retrospective Cohort Study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePPD occurred in 4.9% of females with HS and 2.1% without HS (risk ratio [RR], 2.31; 95% CI, 2.10\u0026ndash;2.54; P \u0026lt; .0001) (Table 1). After matching for age at childbirth and race and ethnicity, PPD remained more common among females with HS (4.9% vs 2.28%; RR, 2.15; 95% CI, 1.82\u0026ndash;2.55; P \u0026lt; .0001).\u003c/p\u003e\n\u003cp\u003eAdditional matching for psychiatric comorbidities attenuated but did not eliminate the association between HS and PPD (RR, 1.35; 95% CI, 1.17\u0026ndash;1.56; P \u0026lt; .0001). In a separately propensity score\u0026ndash;matched cohort that additionally included obstetric complications, HS remained associated with higher PPD incidence (RR, 1.32; 95% CI, 1.14\u0026ndash;1.52; P = .0002).\u003c/p\u003e\n\u003cp\u003eAmong patients without prior antidepressant or anxiolytic use, new prescriptions for these medications were more common in patients with HS than in those without HS (11.5% vs 8.0%; RR, 1.44; 95% CI, 1.28\u0026ndash;1.62; P \u0026lt; .0001). Among patients with HS, PPD incidence did not differ by biologic treatment exposure (RR, 0.83; 95% CI, 0.49\u0026ndash;1.40; P = .48).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePart B: Case\u0026ndash;Control Study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDemographic characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRace and ethnicity differed between HS patients with and without PPD (\u0026chi;\u0026sup2; P = .0075), with patients with PPD more frequently White and less frequently Asian (\u003cstrong\u003eTable 2, Supplementary Table S3\u003c/strong\u003e). No differences were observed by income source, insurance, employment or caregiving status \u0026nbsp;(single parent, co-parenting, or no custody of children).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePsychiatric and substance use history\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrior depression (P = .0396) and trauma- or stressor-related disorders (P = .0190) were more common among patients with PPD.(\u003cstrong\u003eTable 2, Supplementary Table S2\u003c/strong\u003e). Substance use history was more common among patients without PPD (P = .0278), while smoking history did not differ.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObstetric characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePeripartum complications, including hypertensive disorders of pregnancy, infection, postpartum hemorrhage, genital tract injury, and breastfeeding-related complications, were more frequent among women with postpartum depression (63.2% vs 26.9%; P \u0026lt; .0001) (\u003cstrong\u003eTable 2, Supplementary Table S2\u003c/strong\u003e). Body mass index (BMI) at delivery was also higher among women with postpartum depression (P = .0012) (\u003cstrong\u003eTable 2, Supplementary Table S1\u003c/strong\u003e). No significant differences were observed for gravidity, parity, planned pregnancy, preterm birth, intrapartum complications, or neonatal intensive care unit admission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHS-related characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with PPD were younger at first clinician-documented HS diagnosis (P = .0001), and patient-reported HS symptoms or diagnosis preceding clinician documentation were less common (P = .0207) (\u003cstrong\u003eTable 2, Supplementary Table S3\u003c/strong\u003e). No differences were observed in Hurley stage at diagnosis or delivery, HS-related healthcare utilization, or HS treatment exposure.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePPD occurs more frequently among patients with HS than among patients without HS, even after accounting for demographic, psychiatric, and obstetric factors. While HS is well recognized to be associated with an increased burden of depression and anxiety, these findings extend that association specifically to the postpartum period (PPP), identifying this interval as a distinct window of vulnerability [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHS frequently flares in the PPP which may increase the physiologic and psychosocial demands of the already demanding PPP [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition, systemic inflammation associated with HS, including elevated levels of TNF\u0026ndash;α, has been implicated in perinatal mood disorders, suggesting a potential shared inflammatory pathway linking HS and PPD [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe case\u0026ndash;control analysis examined whether specific demographic, psychiatric, obstetric, or HS-related characteristics differed between patients with HS with and without PPD. After adjustment for multiple comparisons, peripartum complications and higher BMI at delivery were most strongly associated with PPD, suggesting that increased physiologic burden during pregnancy may contribute to elevated PPD risk among patients with HS. Markers of HS severity, including Hurley stage, treatment exposure, and HS-related hospitalizations, did not differ between groups, consistent with prior studies showing that depression and anxiety risk in HS is not strongly correlated with disease severity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has several limitations. Both analyses were retrospective and relied on electronic health record data, which may be subject to misclassification and residual confounding. Postpartum depression was identified using diagnostic codes rather than standardized screening instruments, which may underestimate prevalence. In the retrospective cohort, patients with major depressive disorder prior to pregnancy were excluded to isolate incident PPD; however, this excluded a high-risk subgroup, potentially limiting generalizability and underestimating overall PPD burden among women with HS. The case\u0026ndash;control analysis was limited by sample size and incomplete longitudinal capture of HS disease activity, precluding multivariable modeling and limiting power to detect modest associations. These findings are hypothesis-generating and require confirmation in prospective studies. If confirmed, women with HS may represent a population warranting closer PPD screening and support.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSources of support that require acknowledgment\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; financial disclosures and conflicts of interest\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e: The data underlying this article cannot be shared publicly due to privacy and ethical restrictions. De-identified patient-level data are available from the Mass General Brigham Research Patient Data Registry upon reasonable request and with appropriate institutional approvals.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChellappan B, Nguyen DDQ, Hoyer P et al (2022) Dermatologic Management of Hidradenitis Suppurativa and Impact on Pregnancy and Breastfeeding. Cutis 109:160\u0026ndash;162\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeivright JR, Villa NM, Grogan T et al (2022) Impact of Pregnancy on Hidradenitis Suppurativa Disease Course: A Systematic Review and Meta-Analysis. Dermatol Basel Switz 238:260\u0026ndash;266\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolgersen N, Rosen\u0026oslash; NAL, Nielsen VW et al (2025) Risk of New-Onset and Recurrent Depression and Anxiety Among Patients With Hidradenitis Suppurativa. JAMA Dermatol 161:1014\u0026ndash;1021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohn E, Palma G, Mastacouris N et al (2024) Incidence of anxiety disorder in adults with hidradenitis suppurativa. Br J Dermatol 191:351\u0026ndash;356\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWright S, Strunk A, Garg A (2020) New-onset depression among children, adolescents, and adults with hidradenitis suppurativa. J Am Acad Dermatol 83:1360\u0026ndash;1366\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWright S, Strunk A, Garg A (2022) Prevalence of depression among children, adolescents, and adults with hidradenitis suppurativa. J Am Acad Dermatol 86:55\u0026ndash;60\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eĐurinec P, Bukvić Mokos Z, Marinović B (2025) The psychosocial effects of hidradenitis suppurativa. Clin Dermatol 43:462\u0026ndash;470\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeboit PE, Patel DU, Cohen JN et al (2025) The Inflammatory Landscape of a Whole-Tissue Explant Model of Hidradenitis Suppurativa. Exp Dermatol 34:e70057\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva-Fernandes A, Conde A, Marques M et al (2024) Inflammatory biomarkers and perinatal depression: A systematic review. PLoS ONE 19:e0280612\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolgersen N, Rosen\u0026oslash; NAL, Nielsen VW et al (2025) Risk of New-Onset and Recurrent Depression and Anxiety Among Patients With Hidradenitis Suppurativa. JAMA Dermatol 161:1014\u0026ndash;1021\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Hidradenitis suppurativa, postpartum depression, perinatal mental health, pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-8981781/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8981781/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eHidradenitis suppurativa (HS) disproportionately affects women of reproductive age and is associated with psychiatric comorbidity, but its relationship with postpartum depression (PPD) is unclear. We conducted two complementary studies to assess PPD risk in HS and associated factors among postpartum patients with HS.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e \u003cb\u003ePart A\u003c/b\u003e: TriNetX EHR data (2005\u0026ndash;2023) were used to identify postpartum females aged 18\u0026ndash;45 years. Patients with pre-delivery HS were compared with those without HS. PPD was defined by ICD-10 codes (F53.0, F32.0\u0026ndash;F32.3) within 365 days postpartum, excluding MDD in the 12 months pre-pregnancy. Cohorts were propensity score\u0026ndash;matched 1:1 on demographics, psychiatric history, and comorbidities.\u003cb\u003ePart B\u003c/b\u003e: In the Mass General Brigham Research Patient Data Registry, we conducted an age-matched case\u0026ndash;control study among postpartum females aged 18\u0026ndash;45 years with dermatologist-confirmed HS. Cases had PPD within 1 year postpartum; controls had no PPD. Demographic, psychiatric/substance use, obstetric, and HS-related factors were compared using univariable tests.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e \u003cb\u003ePart A\u003c/b\u003e: PPD occurred in 4.9% of patients with HS versus 2.1% without HS (RR 2.31; 95% CI, 2.10\u0026ndash;2.54; P\u0026lt;.0001). The association persisted after matching for age and race/ethnicity (RR 2.15; 95% CI, 1.82\u0026ndash;2.55; P\u0026lt;.0001) and after additional adjustment for psychiatric comorbidities and obstetric complications (RR 1.32; 95% CI, 1.14\u0026ndash;1.52; P=.0002). New antidepressant/anxiolytic prescriptions were higher in HS (RR 1.44; 95% CI, 1.28\u0026ndash;1.62; P\u0026lt;.0001).\u003cb\u003ePart B\u003c/b\u003e: Among 46 cases and 37 controls (95 vs 67 deliveries), race/ethnicity differed (cases more often White, less often Asian; χ\u0026sup2; P=.0075). Prior depression (P=.0396) and trauma- or stressor-related disorders (P=.0190) were more common in cases along with peripartum complications (63.2% vs 26.9%; P\u0026lt;.0001), and higher BMI at delivery (P=.0012). Cases were younger at first clinician-documented HS diagnosis (P=.0001) and less often reported HS symptoms preceding diagnosis (P=.0207). No differences were observed in Hurley stage, HS-related utilization, or treatment exposure.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHS may represent a postpartum window of heightened depression risk, with increased PPD incidence after adjustment for confounders. Peripartum complications, higher BMI, and psychiatric history may identify highest-risk patients. Prospective studies are needed to confirm predictors and inform screening.\u003c/p\u003e","manuscriptTitle":"Postpartum Depression Risk in Hidradenitis Suppurativa: A Matched Cohort Study and Case–Control Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-13 07:22:32","doi":"10.21203/rs.3.rs-8981781/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-05-05T21:47:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-28T12:25:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-28T12:21:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2026-02-26T22:13:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b488b37c-ca29-497b-92f2-b52220859ffe","owner":[],"postedDate":"May 13th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewersInvited","content":"20","date":"2026-05-05T21:47:19+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T07:22:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-13 07:22:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8981781","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8981781","identity":"rs-8981781","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}