Mixed Findings on Link Between Eczema and Neuropsychiatric Conditions

Adults with atopic dermatitis (AD) had a significantly higher prevalence of anxiety, depression, and obsessive-compulsive disorder (OCD) across all severities of the skin disorder, a large retrospective analysis showed.

The strongest association was with OCD, which occurred almost 50% more often in patients with AD. Anxiety and depression were more modestly elevated (14% higher) but still significantly different from individuals without AD. Additionally, patients with mild or moderate AD had higher rates of autism, attention deficit-hyperactivity disorder (ADHD), bipolar disorder, and suicide.

The study adds to a substantial volume of evidence linking AD to neuropsychiatric disorders, but is one of the few to investigate the long-term impact of AD severity, reported Joel Gelfand, MD, of the University of Pennsylvania in Philadelphia, and co-authors in the Journal of the European Academy of Dermatology and Venereology (JEADV).

"Clinicians should inquire about mental health in patients with AD," the authors concluded. "Further research is needed to characterize the mechanisms that link AD to individual neuropsychiatric outcomes and to optimize screening and treatment approaches for reducing such morbidities in AD."

A separate analysis of the same British database, published in JEADV earlier this year, showed no clear association between AD and the prevalence of neuropsychiatric disorders in children and adolescents.

"However, age was an important modifying factor, with older children having increased rates of anxiety, depression, bipolar disorder, and suicidality with respect to AD," Gelfand and co-authors wrote of the earlier study in children and adolescents.

Several studies have demonstrated associations between AD and depression, anxiety, suicidality, ADHD, and autism. Depression, anxiety, and suicidality have been investigated most often. Gelfand and colleagues conducted this retrospective cohort study to continue the investigation of AD and neuropsychiatric disorders and to collect longitudinal data on the effects of AD severity on neuropsychiatric disorders.

Consistent with previous studies, the most commonly diagnosed neuropsychiatric disorders were depression (23.69%) and anxiety (17.10%). Corresponding prevalence of the same two disorders in the control group were 19.67% and 14.18%. The third most common neuropsychiatric outcome was suicidal ideation/attempted suicide (4.38% vs 3.57%).

The adjusted analysis yielded significant hazard ratios (HRs) for the AD group versus the no-AD group:

• OCD - HR 1.48 (95% CI 1.38-1.58)
• Anxiety - HR 1.14 (95% CI 1.13-1.15)
• Depression - HR 1.14 (95% CI 1.13-1.15)

Results were similar across all degrees of AD severity.

Autism risk was increased significantly in patients with mild (HR 1.55, 95% CI 1.26-1.89) and moderate AD (HR 1.40, 95% CI 1.07-1.83). Bipolar disorder was significantly increased for the entire AD cohort (HR 1.12, 95% CI 1.04-1.22) but was driven by moderate AD (HR 1.20, 95% CI 1.07-1.35). Overall, AD had no association with schizophrenia, but patients with severe AD had a lower risk of schizophrenia (HR 0.47, 95% CI 0.23-0.94).

The risk of suicidal ideation/attempt was higher in all patients with AD (HR 1.10, 95% CI 1.07-1.14) but analysis by AD severity showed that the results were driven by patients with mild (HR 1.08, 95% CI 1.05-1.12) or moderate AD (HR 1.14, 95% CI 1.10-1.19). Completed suicide was increased in patients with mild (HR 1.37) or moderate AD (HR 1.12) but decreased in those with severe AD (HR 0.43).

Reasons for the lack of association of severe AD with several outcomes are unclear, the authors stated. One possible explanation is that therapies used to treat severe AD may reduce the risk of neuropsychiatric comorbidities. Another possibility relates to the time-updated nature of the severity categories, which could have led to depletion of some categories or misclassification of severe AD.

Investigators queried an electronic health record system for general practices in the U.K. from 1994 to 2015. They identified 625,083 adults with AD, who were matched to 2,678,888 adults without AD. Diagnosis of AD was based on diagnostic codes for the condition and for AD-related therapy. AD severity was determined by the type of therapy, including referral to a dermatologist.

The outcomes evaluated were anxiety, depression, bipolar disorder, schizophrenia, ADHD, autism, OCD, suicidality and completed suicide. The neuropsychiatric conditions were determined by diagnostic codes, as well as death records associated with completed suicide. Patients with a history of any of the outcomes at baseline were excluded. Data were adjusted for age, sex, socioeconomic status, body mass index, smoking and drinking status, asthma, and allergic rhinitis.

Patients with AD had a median age of 47, and women accounted for 60% of the study group. Median follow-up was 5 years.

The prior study of AD and neuropsychiatric disorders in children included 409,431 children with AD, matched to 1,809,029 without AD. The results showed no significant association between AD and anxiety, ADHD, autism, bipolar disorder, suicidal ideation/attempt, or completed suicide. Children with AD were less likely to develop depression (HR 0.93, 95% CI 0.91-0.95) or schizophrenia (HR 0.72, 95% CI 0.54-0.95) but more likely to develop OCD (HR 1.26, 95% CI 1.16-1.37).

"However, there was substantial variation by AD severity and age in both the direction and magnitude of effect for many of the neuropsychiatric conditions examined," the authors noted.

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