The factors that contribute to the development of psoriatic arthritis (PsA) among patients with psoriasis are not well known; however, systemic inflammation is believed to be important. On the basis of recent laboratory work demonstrating that major depressive disorder (MDD) is associated with increased systemic inflammation, we hypothesized that patients with psoriasis who develop MDD are at increased risk of subsequently developing PsA. We utilized The Health Improvement Network, a primary care medical records database, to identify 73,447 individuals with psoriasis. Patients were followed up to 25 years until the development of the primary outcome of PsA or the censor date. The exposure of interest was the development of MDD. Cox proportional-hazards models showed that patients with psoriasis who developed MDD were at significantly increased risk of subsequently developing PsA compared with patients who did not develop MDD, even after accounting for numerous covariates (hazard ratio 1.37, 95% confidence interval 1.05-1.80, P = 0.021). This result was maintained through numerous sensitivity analyses. These data support the hypothesis that MDD increases the risk of developing PsA among patients with psoriasis, suggesting a need for heightened prevention and management of MDD in patients with psoriasis.

IMPORTANCE Alopecia areata (AA) is an autoimmune disease characterized by hair loss that can impose a substantial psychological burden on patients, including major depressive disorder (MDD), yet many patients report mental health symptoms prior to the onset of AA. As such, there may be an association between MDD and AA that acts in both directions.OBJECTIVE To assess the bidirectional association between MDD and AA. DESIGN, SETTING, AND PARTICIPANTSThis population-based retrospective cohort study included patients 10 to 90 years of age registered with The Health Improvement Network in general practices in the United Kingdom between January 1, 1986, and May 16, 2012. Statistical analysis was conducted from August 17, 201717, , to April 23, 2018 To assess the risk of AA, the following 2 cohorts were defined: patients with an incident diagnosis of MDD (exposure) and a reference general population cohort. To assess the risk of MDD, the following 2 cohorts were defined: patients with an incident diagnosis of AA (exposure) and a reference general population cohort. Person-time was partitioned into unexposed and exposed time in the exposure cohorts. MAIN OUTCOMES AND MEASURESIn the analysis of the risk of AA, development of incident AA during follow-up was considered the main outcome measure. In the analysis of the risk of MDD, development of incident MDD during follow-up was considered the primary outcome measure. RESULTSIn the analysis of the risk of AA, 405 339 patients who developed MDD (263 916 women and 141 423 men; median age, 36.7 years [interquartile range, 26.6-50.5 years]) and 5 738 596 patients who did not develop MDD (2 912 201 women and 2 826 395 men; median age, 35.8 years [interquartile range, 25.3-52.6 years]) were followed up for 26 years. After adjustment for covariates, MDD was found to increase the risk of subsequently developing AA by 90% (hazard ratio, 1.90; 95% CI, 1.67-2.15; P < .001). Antidepressants demonstrated a protective effect on the risk of AA (hazard ratio, 0.57; 95% CI, 0.53-0.62; P < .001). In the analysis of the risk of MDD, 6861 patients who developed AA (3846 women and 3015 men; median age, 31.5 years [interquartile range, 18.2 years]) and 6 137 342 patients who did not develop AA (3 172 371 women and 2 964 971 men; median age, 35.9 years [interquartile range, 27.0 years]) were followed up for 26 years. After adjustment for covariates, AA was found to increase the risk of subsequently developing MDD by 34% (hazard ratio, 1.34; 95% CI, 1.23-1.46; P < .001).CONCLUSIONS AND RELEVANCE These temporal analyses suggest that, while patients with AA are at risk for subsequently developing MDD, having MDD also appears to be a significant risk factor for development of AA, with antidepressant use confounding this risk.

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This research is made possible through the generous support of Exciton Technologies Inc.

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