From the Journals

Bidirectional relationship found between depression, vitiligo



Vitiligo and major depressive disorder have a bidirectional relationship, according to a new study that examined data from a cohort of more than 6 million people.

“Ultimately, this suggests that mental health appears to play a large role in the pathogenesis of autoimmune diseases like vitiligo, which in turn can increase the risk of MDD, especially in younger patients,” wrote Isabelle Vallerand, PhD, and her colleagues. The report is in the Journal of the American Academy of Dermatology.

Dr. Vallerand and her colleagues found that patients with major depressive disorder (MDD, n = 405,397) had a 64% increased risk of vitiligo, compared with a referent cohort (n = 5,739,048; 95% confidence interval, 1.43-1.87; P less than .0001). Conversely, patients who had vitiligo also were at an increased risk of MDD. Patients who were younger than 30 years old at diagnosis (n = 7,104) had a hazard ratio of 1.31 for MDD (P less than .0001), compared with 1.22 for patients aged 30 years and older (P = .001).

Individuals who took antidepressants, whether or not they also had an MDD diagnosis, had a decreased risk for vitiligo.

Though it’s known that vitiligo increases the risk of MDD, less clarity has been in the literature about whether the converse also might be true. “The question of whether vitiligo onset can be precipitated by MDD has received less attention, despite the notion that patients often ask their dermatologists if stress or depression may have contributed to their disease,” wrote Dr. Vallerand, an epidemiologist and medical student at the University of Calgary, Alberta, and her colleagues.

There is a biologic plausibility for a bidirectional relationship, said Dr. Vallerand and her colleagues, since depression can boost systemic inflammation, and the risk for autoimmune disease such as vitiligo can be increased by proinflammatory states.

Access to a large dataset gave Dr. Vallerand and her collaborators the numbers to look at the relationship between vitiligo and MDD in the context of potential confounders, and to correct for those in their statistical analysis. Using medical records from The Health Improvement Network (THIN) database in the United Kingdom, the investigators conducted two independent population-based cohort studies. Each looked at risk in one direction of the MDD-vitiligo association.

The first analysis looked at MDD as a risk factor for vitiligo, following all patients with an incident diagnostic code for MDD. Patients without the MDD diagnosis code were the referent cohort. Patients in each cohort were followed until they reached the outcome of interest – a diagnosis of vitiligo – or were censored. Patients who had a vitiligo diagnosis before receiving an MDD diagnosis were not included.

The second analysis examined whether vitiligo was a risk factor for MDD, with a similar design that used nonvitiligo patients as the referent cohort. This analysis followed all patients until a diagnosis of MDD was recorded, or patients were censored. Again, patients with MDD diagnoses that came before the vitiligo diagnosis were excluded.

For the analysis of risk of vitiligo, the investigators looked at the effects of multiple covariates, including age, sex, alcohol use and smoking status, socioeconomic status, medical comorbidities, and whether patients were taking antidepressants. The covariates included in the analysis of risk of MDD were age, sex, medical comorbidities, and type of vitiligo treatment.

After the researchers determined unadjusted hazard ratios, each covariate was removed one at a time to see where there were substantial changes to the HR. Two additional models, one unadjusted and one that fully adjusted for all covariates, also were built.

The sensitivity analyses showed “an overall protective effect of antidepressants among both cohorts,” wrote Dr. Vallerand and her colleagues. The incidence rate of vitiligo among patients with MDD using antidepressants was 19.7 per 100,000 person-years, compared with 27.5 among MDD patients not using antidepressants (P = .0053).

“Similarly, those in the referent cohort who used antidepressants had about half the risk of vitiligo,” compared with the nonusers in the referent group, the investigators said. Serotonin also is present in the skin, and neurons and melanocytes share embryonic ectodermal origins, Dr. Vallerand and her colleagues said. Though the exact mechanisms are not known, patients with vitiligo may have lower skin serotonin, so there’s a potential role for serotonergic medication in the incidence of vitiligo in the THIN cohorts, they noted.

Though younger patients with vitiligo were at higher risk for MDD than were those aged 30 years and older, the overall cohort of individuals with vitiligo still had an unadjusted elevated risk for MDD, compared with the referent cohort (HR 1.27; 95% confidence interval, 1.16-1.40; P less than .0001).

“Unexpectedly, the magnitude of the reciprocal association was highest with MDD being a risk factor for vitiligo,” wrote Dr. Vallerand and her colleagues. “This highlights the notion that mental health may have a greater impact on the body, specifically with dermatologic manifestations, than previously thought.”

Some misclassification of both conditions is likely in such a large dataset, the investigators acknowledged. Also, subclinical depression was not evaluated, and there was no way to track the severity of either depression or vitiligo, they noted. Still, the big data approach “renders this one of the largest studies on psychodermatology to date,” said Dr. Vallerand and her colleagues, and the independent bidirectional analyses support causality.

Dr. Vallerand is a partner in a pharmaceutical consulting firm, GlacierRX, and was funded by Alberta Innovates. The authors reported having no conflicts of interest.

SOURCE: Vallerand IA et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2018.11.047.

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