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. 2026 Jul 31;105(31):e50036. doi: 10.1097/MD.0000000000050036

Sex differences in the association between depressive symptoms and psoriasis

Xiujuan Wen a,b, Qirui Deng a,b, Yue Cao b,c, Hongfeng Tang a,*
PMCID: PMC13433124  PMID: 42536569

Abstract

Psoriasis is a prevalent chronic inflammatory skin condition that is also classified as an autoimmune disorder. There is an established interplay between autoimmune diseases and mental health issues, particularly depression. Consequently, this study aims to explore the association between depression and psoriasis. This cross-sectional study examined data from participants in the National Health and Nutrition Examination Survey from 2009 to 2014. Depression information was gathered through the patient health questionnaire Patient Health Questionnaire-9 (PHQ-9). Weighted logic was applied to investigate the correlation between depression and psoriasis. In addition, subgroup analyses were conducted to investigate potential interactions. Out of the total 15,863 patients enrolled in the study, out of which 438 had a prior diagnosis of psoriasis. Weighted logistic regression analysis showed a direct relationship between the PHQ-9 result and psoriasis. Moreover, the occurrence of psoriasis was more prevalent among males compared to females in the case of depression. The restricted cubic spline curve demonstrated a positive linear correlation between psoriasis and depression, showing a turning point at 2. A subgroup examination was performed and revealed a connection between gender and depression. A significant positive relationship exists between the increase in PHQ-9 depression scores and the increased likelihood of having psoriasis, which varies among different genders.

Keywords: depression score, depressive symptoms, gender differences, NHANES, psoriasis

1. Introduction

Psoriasis is classified a complex immune-mediated disease due to its association with various comorbidities, such as psychiatric, metabolic, arthritic, and cardiovascular disorders.[1,2] Concurrently, psoriasis is a genetic skin condition influenced by the immune system. The pathological mechanisms are complex, involving interactions among the innate and adaptive immune systems.[3] Psoriasis, being an incurable condition, significantly affects the lives of individuals dealing with it. Thus, it is imperative to increase awareness about psoriasis without delay.

Depression, a prevalent mood disorder marked by enduring low mood, sadness, hopelessness, and feelings of worthlessness,[4] has seen a notable rise in occurrence following the impact of the recent COVID-19 pandemic.[5] While there is evidence suggesting that psoriasis can trigger depression, it seems that the relationship is bidirectional.[6,7] A mounting body of scientific evidence shows a link between depression and the immune system.[8–10] In addition, treating psoriasis systemically might help reduce depressive symptoms to a certain extent.[11,12] This implies that the close connection between psoriasis and depression could arise from the shared inflammatory and immune mechanisms. Gender plays a significant role in influencing how individuals respond to antidepressant medication, as demonstrated by research and studies.[13,14] Despite research indicating higher likelihood of depression among women with psoriasis compared to men,[15–18] there has been limited evaluation of gender variances in the onset of psoriasis among depressed individuals. Considering this, it is valuable to investigate investigate the cross-sectional association between depression and psoriasis.

The aim of our study was to investigate the relationship between depression and psoriasis using the National Health and Nutrition Examination Survey (NHANES), with significant differences noted between males and females.

2. Methods

2.1. Study population

NHANES is a nationwide survey administered biennially, providing cross-sectional data representative of the entire US populace. This study used the 2009–2014 NHANES continuous cycle data sets. All NHANES programs received backing from the Ethics Review Board of the National Center for Health Statistics, and written informed consent was obtained from participants during enrollment. The study originally included 30,468 participants. After excluding 14,595 individuals without PHQ9 data and 10 individuals lacking psoriasis data, we analyzed a remaining cohort of 15,863 participants to examine the association between depression and psoriasis. A graphical illustration of our sample selection methodology is depicted in Figure 1.

Figure 1.

Figure 1.

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Flow chart for the inclusion and exclusion criteria.

2.2. Measurement of depressive symptoms

The 9-item Patient Health Questionnaire-9 (PHQ-9) is employed for diagnosing depression. This self-administered instrument assesses 9 depressive symptoms, grounded in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria.[19] Studies have shown that the PHQ-9 serves as a precise and dependable instrument for the screening of depression. This instrument serves to evaluate depressive manifestations observed within the preceding fortnight. It includes 9 categories of symptom response that are answered on a 4-point scale: 0 representing no symptoms, 1 indicating rare symptoms occurring a few days, 2 marking frequent symptoms on more than half of the days, and 3 denoting almost constant symptoms nearly every day. The overall score spans from 0 to 27, where elevated scores denote more severe depressive symptoms. Within the context of this research, 5 was the baseline cutoff for depression.[20,21]

2.3. Diagnosis of psoriasis

Psoriasis diagnosis was identified through the analysis of the “medical conditions” portion of the questionnaire data. In this research, we classified psoriasis as being present in individuals who answered “yes” to the question, “Have you ever been informed by a healthcare provider that you have psoriasis?.”

2.4. Selection of covariates

The covariates considered in this study include age, sex, education level, race, income-to-poverty ratio (PIR), body mass index (BMI, kg/m2), alcohol consumption and smoking status. Self-reported race was categorized as White, Black, Mexican, and Other. Educational qualifications were divided into 3 categories: high school diploma, less than a high school diploma, and more than a high school diploma. The PIR was used as a proxy for socio-economic status. Smoking was defined as having smoked at least 100 cigarettes, and alcohol consumption was defined as having had at least 12 drinks in a lifetime. Hypertension and diabetes mellitus were identified through self-reporting. We addressed the issue of missing data by employing the missForest R package, which utilizes a random forest algorithm known for its high computational efficiency when handling high-dimensional datasets with both categorical and continuous variables.[22]

2.5. Statistical analysis

The statistical analysis adhered to the guidelines set forth by the Centers for Disease Control and Prevention, incorporating appropriate NHANES sampling weights and utilizing complex multi-stage cluster survey techniques. Categorical variables were displayed using frequencies and percentages (%), whereas continuous variables were represented by the mean along with the standard error (SE). Weighted t-tests were utilized for the comparison of means relating to continuous variables. Weighted chi-square tests were applied to evaluate notable variances in general attributes for categorical variables. We performed multiple imputation on variables with missing data below 10%. A weighted multivariable logistic regression analysis was conducted to investigate the association between depressive symptoms and psoriasis. A series of regression models were constructed through a process of stepwise adjustment for covariates: Model 1: No adjustments were applied; Model 2: Age, gender, race, BMI, PIR, and education level were taken into consideration; Model 3: Age, gender, race, BMI, PIR, education level, drinking behavior, and smoking habits were considered and adjusted for in the study. Furthermore, restricted cubic spline models were applied to both the overall populace and distinct genders to study how depression is linked with psoriasis. The analysis was performed utilizing R software (version 4.4.0, R Core Team). A significance level of 2-tailed P < .05 was applied.

3. Results

3.1. Baseline characteristics

This study incorporated a cohort of 15,863 participants, of whom 438 (2.8%) had a documented history of psoriasis. The distribution of gender among the participants was as shown: 49.42% were male and 50.57% were female. Mexican constituted 14.37% of the sample, while Other individuals accounted for 21.09%. The remaining participants identified as Whites (43.14%), and Blacks (21.40%). Individuals with a history of psoriasis are typically older, predominantly Whites, and higher likelihood of experiencing depression (P = .004) in comparison to individuals without a history of psoriasis. Moreover, these individuals exhibit a proclivity towards higher smoking frequency, and have previously experienced diabetes and high blood pressure. The statistical analysis indicated no statistically significant differences between the 2 groups in terms of PIR, BMI, gender, educational level, and alcohol consumption frequency (P > .05) (Table 1).

Table 1.

The baseline characteristics by quartiles of patients with and without psoriasis.: National Health and Nutrition Examination Survey 2009–2014

Variable No history of psoriasis (n = 15425[97.2%]) History of psoriasis (n = 438[2.8%]) P value
Age 46.346 (0.353) 50.515 (0.987) <.0001
PIR 2.905 (0.050) 3.046 (0.113) .15
Score 3.043 (0.069) 3.885 (0.274) .003
BMI 28.837 (0.105) 29.674 (0.443) .061
Race <.0001
  Black 3347 (11.291) 48 (5.243)
Mexican 2240 (8.617) 39 (4.546)
  Other 3251 (12.815) 95 (10.825)
  White 6587 (67.276) 256 (79.386)
Gender .755
  Female 7798 (50.807) 225 (51.641)
  Male 7627 (49.193) 213 (48.359)
Education .52
High school diploma 3613 (16.130) 91 (13.822)
Less than high school 3460 (21.672) 99 (21.551)
Above high school 8352 (62.198) 248 (64.627)
Smoke <.001
  No 8751 (56.742) 190 (43.732)
  Yes 6674 (43.258) 248 (56.268)
Alcohol.user .163
  No 2323 (11.641) 55 (9.530)
  Yes 13,102 (88.359) 383 (90.470)
Diabetes .004
  No 13,612 (90.987) 360 (86.072)
  Yes 1813 (9.013) 78 (13.928)
Hypertension <.001
  No 10,074 (68.486) 234 (57.670)
  Yes 5351 (31.514) 204 (42.330)
PHQ9 .004
 [0–4] 11,598 (77.082) 290 (69.588)
 [5–27] 3827 (22.918) 148 (30.412)
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BMI = body mass index, PHQ-9 = Patient Health Questionnaire-9, PIR = the ratio of family income to poverty. Mean ± SD for continuous variables: the P-value was calculated by weighted linear regression model. n (%) for categorical variables: the P-value was calculated by a weighted chi-square test.

3.2. Association of depressive symptoms with psoriasis prevalence

With reference to Table 2, the correlation between depression and psoriasis is illustrated. The association between PHQ9 scores and psoriasis was robust and significant in Model 1 (odds ratio [OR] = 1.04 [95% CI 1.02,1.06]), Model 2 (OR = 1.05 [95% CI 1.02,1.07]), and Model 3 (OR = 1.04 [95% CI 1.01,1.07]), as compared to subjects without depression. Conversely, subsequent examinations following the assessment of depression using a PHQ9 score above 5 as the threshold value, Model 1 (OR = 1.47 [95% CI 1.14,1.90]), Model 2 (OR = 1.50 [95% CI 1.13,2.00]), and Model 3 (OR = 1.44 [95% CI 1.80,1.90]) confirmed the link between depression and psoriasis, with a significant increase in the strength of this correlation. The link between depression and psoriasis among men persisted following various adjustments for diverse confounders. Nevertheless, the correlation between depression and psoriasis in females did not exhibit statistical significance across all models (P > .05).

Table 2.

Association of depressive symptoms with psoriasis in a multivariate regression analysis

Variable Model 1 Model 2 Model 3
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Overall PHQ9 Score 1.04 (1.02,1.06) <.001 1.05 (1.02,1.07) .001 1.04 (1.01,1.07) .01
Depression 1.47 (1.14,1.90) .004 1.50 (1.13,2.00) .01 1.44 (1.08,1.90) .01
Male PHQ9 Score 1.07 (1.03,1.10) <.001 1.09 (1.04,1.13) <.001 1.08 (1.04,1.12) <.001
Depression 1.63 (1.04,2.55) .03 1.90 (1.15,3.14) .01 1.79 (1.08,2.97) .03
Female PHQ9 Score 1.02 (0.99,1.05) .16 1.01 (0.98,1.04) .51 1.00 (0.97,1.04) .91
Depression 1.36 (0.97,1.90) .07 1.25 (0.86,1.80) .23 1.21 (0.84,1.75) .30
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Model 1: no covariates were adjusted.

Model 2: age, gender, race, BMI, PIR, and education level were adjusted.

Model 3: age, gender, race, BMI, PIR, education level, drinking, and smoking were adjusted.

3.3. Subgroup analysis

The study examined the relationship between depression and psoriasis by analyzing data from distinct demographic subgroups based on gender, ethnicity, level of education, drinking habits, smoking status, diabetes, and hypertension (Fig. 2). Statistically significant interactions were not found for ethnicity (P = .16), educational background (P = .41), smoking (P = .83), alcohol use (P = .42), the presence of diabetes (P = .51), or hypertension (P = .86). Male individuals diagnosed with depression exhibited a significantly elevated likelihood of psoriasis onset (P < .001), characterized by an OR of 1.08 and a 95% confidence interval (CI) between 1.04 and 1.12. Conversely, among female patients, there was a lack of statistically significant variance in the propensity to develop psoriasis associated with depression. Additional examination revealed a correlation between gender and depression in cases of psoriasis. To examine the link between depression and psoriasis in males and females, we employed restricted cubic spline analysis to investigate the impact of gender variables on this connection (Fig. 3). A notable correlation was found between the PHQ9 score and depression (P for overall = .001, P for nonlinear = .72). Among men, the odds ratio of psoriasis steadily rose with higher PHQ9 scores (P for overall < .001, P for nonlinear = .96), whereas this pattern was not observed in women. The influence of gender variables is paramount in understanding the correlation between depression and psoriasis, offering fresh insights for future studies.

Figure 2.

Figure 2.

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Subgroup analyses on the effect of interaction between the covariates and Patient Health Questionnaire 9 score on the prevalence of Psoriasis.

Figure 3.

Figure 3.

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Correlation between PHQ9 and psoriasis. (A)Nonlinear association between the PHQ9 and psoriasis by restricted cubic spline regression in total. (B) The sex-specific association between the PHQ9 and psoriasis. Red for males, blue for females. The black dashed line represents the position where the odds ratio (OR) equals 1, with the 95% confidence interval (CI) indicated by shaded areas.

4. Discussion

We performed a cross-sectional study involving 15,863 NHANES participants to investigate the correlation between depression and psoriasis. Our results indicate a positive correlation between PHQ9 scores and the prevalence of psoriasis. Specifically, we observed a significant link between the prevalence of psoriasis and depression in men as opposed to women. Our findings remained consistent even after accounting for relevant covariates. This discovery offers insights into the underlying mechanisms between the 2 conditions, and provides healthcare professionals with a foundation for monitoring psoriasis occurrence and implementing early screening in men with depression.

In our research, we observed that individuals with depressive symptoms, as indicated by a score of 5 or more on the PHQ scale, showed a stronger association with psoriasis prevalence (OR, 1.47;95% CI, 1.14 to 1.90) . To our knowledge, our research is a groundbreaking attempt to explore the connection between depressive symptoms and psoriasis by analyzing the NHANES dataset. While various studies have confirmed a higher likelihood of depression in individuals with psoriasis,[23–25]along with recent research showing a 2-way causative link between psoriasis and depression,[7]the exact mechanism behind this connection remains unknown. Our research results align with prior studies reporting a significant association between depression and psoriasis occurrence.[26] This underscores a clear and strong connection between depression and psoriasis. Some potential evidence suggests a potential bi-directional association between gender disparities in depression and psoriasis, possibly through immune-mediated inflammatory reactions.

The observed depression in psoriasis patients may stem partly from elevated pro-inflammatory cytokines (e.g., TNF-α, IL-17/23) rather than solely psychological distress.[27,28] These psoriasis-associated cytokines, secreted by activated T cells and dendritic cells,[29] can directly induce neurobiological changes linked to depressive symptomatology.[30] Notably, 62% of psoriasis patients experience comorbid depression,[31] underscoring clinical relevance. Conversely, depression independently exhibits elevated inflammatory markers (CRP, IL-6) mirroring psoriasis profiles,[32–36]even without inflammatory comorbidities.[34,35] Experimental IFN-α administration exacerbates depressive symptoms,[36] while depression involves Th17/Treg imbalance reversible by antidepressants.[37,38] Critically, anti-cytokine therapies for psoriasis alleviate depression, and anti-inflammatory agents improve depressive symptoms.[39] This bidirectional crosstalk suggests shared immune-mediated inflammatory pathways,[40] positioning both disorders on a common etiological spectrum.

So far, relatively few studies have investigated whether gender differences will influence the association between systemic inflammatory markers and depressive symptoms. Our study has discovered, for the first time, that the occurrence of psoriasis is more common in male patients with depression than in female patients. However, this observed male-specific association warrants cautious interpretation. The published data regarding the gender distribution of psoriasis patients with depression is somewhat conflicting. Traditionally, psoriasis incidence has been regarded as relatively balanced between genders.[41,42] Yet, recent insights suggest gender-specific impacts on disease severity.[43,44] Men might be less likely to report depressive symptoms or seek help for mental health concerns compared to women,[45] potentially leading to an under-identification of depression in men within the general population. Consequently, the men identified with depression in our study might represent a subset with more severe symptoms or comorbidities, including psoriasis. Conversely, women generally access healthcare more frequently,[46] potentially increasing the likelihood of psoriasis diagnosis regardless of depression status, which could dilute the observed association in women.

A wealthof data underscores the divergent genetic expression signatures in depression for men and women.[47,48] Such disparities may shed light on the distinct clinical manifestations of depression and the varying effectiveness of treatment strategies among genders. Multiple research studies have highlighted an increased likelihood of secondary psychiatric coexisting conditions in women with psoriasis.[49,50] Depressed women commonly display elevated levels of IFN-γ, leptin and IL-8, while showing lower levels of both IL-5 and the anti-inflammatory adiponectin, in comparison to their healthy counterparts.On the contrary, men do not exhibit notable differences in these biomarkers when comparing healthy individuals to those with depression.[51] In a subset of individuals with depression, levels of pro-inflammatory markers in the bloodstream are elevated.[52,53] Specifically, there is a correlation between increased CRP levels and depression in men, while this association is not observed in women.[54] Despite this, the underlying mechanisms of gender differences in psoriasis prevalence among those with depression have been further scrutinized.

Our study boasts several notable strengths. Initially, our research, through gender-based analyses, has for the first time revealed disparities in the incidence of psoriasis between men and women with depression. This revelation paves the way for subsequent investigations to delve into the factors contributing to the increased susceptibility of men to psoriasis. Secondly, our study breaks new ground by examining gender-related risks for psoriasis specifically within the depressed population, a perspective that has been overlooked in previous studies which have mainly concentrated on individual factors within either psoriasis or depression cohorts. Lastly, using a nationally representative NHANES sample gives our study strong statistical power, facilitating the control of confounding elements and enhancing the generalizability of our results to the U.S. population as a whole.

Despite making notable contributions, our research acknowledges certain limitations. Firstly, the cross-sectional design of the study restricts our capacity to infer causal relationships from the identified associations. Secondly, a significant methodological limitation stems from the assessment of psoriasis status. Psoriasis diagnosis was based solely on participants’ self-reported lifetime history, without clinical verification. This approach carries a substantial risk of misclassification (e.g., due to recall bias, misunderstanding the question, or confusion with other dermatoses like eczema or seborrheic dermatitis). Thirdly, a major limitation is the lack of adjustment for key unmeasured confounders, specifically clinical psoriasis severity and systemic treatment history. The NHANES dataset does not contain information on psoriasis subtype, disease severity, duration, or systemic treatment; therefore, we were unable to assess or adjust for these potential confounders. This absence limits the extent to which we can interpret the observed association, particularly the sex-specific differences and underscores the need for future studies that include these key variables. Fourthly, the reliance on participants’ single self-assessment of depressive symptoms via the PHQ-9, without clinical validation, presents another methodological constraint. Furthermore, due to the limited number of participants with psoriasis and a PHQ-9 score ≥ 10 (moderate-to-severe depression), we could not reliably assess the consistency of the association across different depression severity thresholds; this requires further investigation in future studies. Fifthly, while our study focuses on physiological sex differences in psoriasis, it pays less attention to gender’s social and psychological aspects. The findings are primarily relevant to the United States, suggesting they may not directly apply to other ethnicities or regions. Further investigation is required to elucidate the pathophysiological mechanisms that might underpin a bidirectional causal relationship between the 2 diseases. Despite the research methodology’s inherent uncertainties, future studies are poised to conduct a more refined investigation into the variances across physiological sex, gender identity, and the unique experiences of non-binary and transgender individuals concerning these health conditions.

5. Conclusion

Our study findings establish an association between depression and psoriasis, indicating that depression is more strongly associated with psoriasis in men than in women. However, to confirm our results, further extensive prospective studies are warranted.

Author contributions

Conceptualization: Xiujuan Wen, Qirui Deng.

Data curation: Yue Cao.

Supervision: Hongfeng Tang.

Writing – original draft: Xiujuan Wen, Qirui Deng.

Writing – review & editing: Yue Cao, Hongfeng Tang.

Abbreviations:

95%CI
95% confidence intervals
BMI
body mass index
NHANES
National Health and Nutrition Examination Survey
OR
odds ratios
PHQ-9
Patient Health Questionnaire-9
PIR
the ratio of family income to poverty
SD
standard deviation

This research was supported by the Guangdong Basic and Applied Basic Research Foundation (Guangdong-Foshan Joint Fund Regional Incubation Programme) (2023A1515140031); Guangdong Provincial Department of Education Characteristic Innovation Project (NO. 2021KTSCX017); Scientific Research Start Plan of Shunde Hospital, Southern Medical University (No. SRSP2021036, SRSP2021005, SRSP2023030, SRSP2023004); Clinical Research Startup Program of Shunde Hospital, Southern Medical University (CRSP2022003) and Foshan Engineering Technology Research Center of Skin Anti-Aging, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

The datasets generated during and/or analyzed during the current study are publicly available. All data generated or analyzed during this study are included in this published article [and its supplementary information files].

This research followed the guidelines set forth in the Declaration of Helsinki and was approved by the Ethics Review Board of the National Center for Health Statistics (NCHS). All participants provided written informed consent.

The authors have no conflicts of interest to disclose.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: www.cdc.gov/nchs/nhanes/.

How to cite this article: Wen X, Deng Q, Cao Y, Tang H. Sex differences in the association between depressive symptoms and psoriasis. Medicine 2026;105:31(e50036).

XW and QD contributed to this article equally.

Contributor Information

Xiujuan Wen, Email: 1369508614@qq.com.

Qirui Deng, Email: 963817092@qq.com.

Yue Cao, Email: caoyuegege@yeah.net.

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