Atopic dermatitis may be associated with schizophrenia, schizoaffective disorder
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Key takeaways:
- AD increased the odds for schizophrenia and schizoaffective disorder.
- Associations remained in multivariable analyses.
- Inflammation may disrupt the blood-brain barrier.
Atopic dermatitis was associated with increased odds for schizophrenia and schizoaffective disorder, according to a study published in Archives of Dermatological Research.
Physicians who treat patients with AD should recognize these associations and collaborate with other providers as needed, Jeffrey M. Cohen, MD, assistant professor of dermatology at Yale University School of Medicine, and colleagues wrote.
“Previous studies have looked into the relationship between eczema and schizophrenia and have produced conflicting results, so the study was done to offer more information to try to better understand whether a relationship exists,” Cohen, who also is director of the psoriasis treatment program and director of safety, dermatology at Yale School of Medicine, told Healio. “Our findings suggest that there is a relationship.”
Study results
The researchers examined data from 13,433 patients with AD (mean age, 60.1 years; 67.7% women; 62% white) and 53,732 matched controls (mean age, 60.1 years; 67.7% women; 62% white) in the National Institutes of Health All of Us Research Program.
Patients with schizophrenia, defined as a psychotic disorder characterized by delusions, hallucinations and/or disorganized behavior with a decline in functional status, included 2% of the AD group and 1.1% of the control group (P < .001).
Patients with schizoaffective disorder, defined as symptoms of schizophrenia along with manic or depressive mood symptoms, included 1.8% of the AD group and 0.5% of the control group (P < .001).
Similarly, a greater proportion of the AD group than control group had depression (38.1% vs. 21.7%) and anxiety (17% vs. 4.4%; P < .001 for both).
Odds ratios after multivariable analyses adjusting for demographics and common comorbidities included 1.64 (95% CI, 1.39-1.93) for schizophrenia and 2.44 (95% CI, 2.01-2.97) for schizoaffective disorder with AD.
Next steps
Previous studies of associations between schizophrenia and schizoaffective disorder with AD have produced conflicting results, the researchers noted, adding that their findings support that these associations exist. Cohen indicated that these findings also are significant for a couple of reasons.
“Firstly, deepening our understanding of the relationships between medical conditions helps improve patient care,” he said. “Secondly, once a relationship between two disorders is established, more work can be done to try to understand why they are associated. This can ultimately help us learn more about both conditions.”
The researchers also suggested that these associations may be due in part to inflammation disrupting the blood-brain barrier considering observations of elevated proinflammatory cytokines, including IL-6 and tumor necrosis factor alpha, abnormal T-cell activation and increased complement activity.
Patients additionally may be predisposed to both AD and schizophrenia because of common pathways of immune-related dysfunction, the researchers continued, although these pathophysiologic mechanisms should be studied further.
The researchers advised physicians who treat AD be aware of these associations so they can collaborate with other providers to facilitate management of these comorbid conditions when necessary.
“These are serious mental health conditions, so allergists or dermatologists seeing patients for eczema who display signs of one of these conditions should be evaluated promptly,” Cohen said.
“The most important thing an allergist or dermatologist can do to help a patient who is suspected of having schizophrenia or schizoaffective disorder is to help connect that person with psychiatric care,” he continued.
Future studies are needed to understand the connection of these disorders on a deeper level by considering the role of inflammation, genetics and other factors, Cohen said.
For more information:
Jeffrey M. Cohen, MD, can be reached at jeffrey.m.cohen@yale.edu.
Perspective
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These study results are interesting and plausible. There is some evidence suggesting that autoimmunity plays a role in the pathophysiology of schizophrenia. This is reflected in two ways.
One is that autoimmune mechanisms may be out of the pathophysiology of the disease itself, meaning that immune reactions to brain proteins are viewed by the immune system as antigens, which triggers an immune reaction that causes the disturbance in the mental functions of patients.
Data including elevated antibody titers and cytokines in blood and cerebrospinal fluid support this hypothesis. In addition, there is a phenocopy of schizophrenia called autoimmune or limbic encephalitis, a condition often mistaken for schizophrenia, which is treated with immunosuppressive medication rather than antipsychotic medication.
The second way this is relevant is that some medications used to treat schizophrenia can elicit immune reactions in some patients. The classic example is clozapine, an atypical antipsychotic that is highly effective but can cause agranulocytosis and myocarditis in some patients. Both adverse reactions are considered immunological responses to the drug.
Studies have suggested that a specific human leukocyte antigen (HLA) haplotype may be associated with vulnerability that is particularly found in Ashkenazi Jews. However, the specificity of this haplotype as a marker of vulnerability has not been sufficiently predictive to make HLA typing cost-effective as a screening test.
As for what allergists and dermatologists can do to determine susceptibility, apart from taking a history of prior allergic reactions, I am not sure what to recommend other than initial vigilance for the response of patients to new treatments that are introduced.
In summary, there is evidence to suggest the association between schizophrenia and/or its treatment with allergic reactions reflecting autoimmunity, but there is no clear diagnostic measure that may detect susceptibility at this time. It is possible that a test for susceptibility will be developed. But, for now, the only thing is to consider schizophrenia and its medications as potential risk factors for this dermatologic reaction.
Perspective
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The findings in this study are interesting because they provide support for an association between AD and schizophrenia and schizoaffective disorder, which are not connections that have been as well-recognized or reported as some other psychiatric comorbidities.
At this point, these findings may not yet suggest an actionable change in treatment and management for dermatologists and allergists in treating patients with AD. However, they serve as a reminder that AD, as a systemic inflammatory condition, has numerous associated comorbidities that should be kept in mind in treating patients holistically.
Next steps in research may be to explore a mechanistic link between AD and schizophrenia and schizoaffective disorder, as well as to assess for these associations in different populations and datasets.
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Fan R, et al. Arch Dermatol Res. 2023;doi:10.1007/s00403-023-02674-7.
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