No link between allergic diseases and mental disorders

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A new study published in Clinical and experimental allergy found that there is little evidence that allergic diseases cause mental disorders or vice versa.

This finding may address a long-simmering issue arising from the high rates of comorbidity between the two sets of conditions.


Dr Ashley Budu-Aggrey

The study was prompted by “the large and growing disease burden posed by the two sets of disorders,” said senior author Ashley Budu-Aggrey, PhD, senior research associate at Bristol Medical School, Bristol, UK. She and her co-authors investigated whether atopic dermatitis (eczema), hay fever, Where asthma is causally linked – in both directions – to mental disorders such as anxiety, depressionneuroticism bipolar disorder, and schizophrenia.

The authors’ ability to infer or disprove causation depended on their use of an epidemiological technique known as Medelian randomization. The technique is used when “it is impractical or unethical to perform a randomized controlled trial,” Budu-Aggrey said in an interview with Medscape Medical News.

Mendelian randomization uses genetic information, which in this case came from genome-wide association studies, to decide questions of causation.

Before using Mendelian randomization, the authors first confirmed the observational associations between the two sets of disorders. They relied on the UK Biobank, a database with information on hundreds of thousands of people. The biobank is a larger database than that used in previous studies.

The strongest observational association found using data from the Biobank was between atopic dermatitis and anxiety. Atopic dermatitis increased the risk of developing anxiety by 63%. Another robust association was between asthma and bipolar disorder. Asthma increased the risk of developing bipolar disorder by 52%. Were these associations causal?

Mendelian randomization using genetic variant data could solve the question. The technique is an epidemiological cousin of a randomized clinical trial. Its main advantages are that it is free from confounding and reverse causal factors.



Dr Stephen Burgess

“The authors took genetic variations associated with an increased risk of allergic disease and tested [by Mendelian randomization] so those with a higher genetic susceptibility to allergic diseases also have a higher risk of mental health disorders, ”wrote Stephen Burgess, PhD, in an email to Medscape. Burgess is a Research Fellow of the Medical Research Council, Unit of Biostatistics, University of Cambridge, Cambridge, United Kingdom.

Analyzes using Mendelian randomization could not reproduce the observational associations of Biobank. Investigators were unable to infer causation. “Mendelian randomization analyzes suggest that allergic disease is not the causative risk factor in this case,” wrote Burgess, who was not in the study.

The clinical implications of the lack of causation were immediately obvious to the authors. Measures to prevent the onset of allergic diseases are unlikely to prevent the onset of mental health problems, and vice versa, they write.

Yet academics never say never. First, the authors hypothesized that interventions aimed at improving – as opposed to preventing – allergic disorders can further improve mental health, and vice versa.

Second, they found a weak but tantalizing causal relationship between hay fever and bipolar disorder in Mendelian randomization analyzes, despite the lack of an association between the two in the Biobank data set. Evidence of a weak causal effect of the genetic risk of hay fever on bipolar disorder would suggest that preventing one may prevent the other.

The limitations of the study include the fact that the genetic studies used for the Mendelian randomization analyzes were stronger for allergic diseases than for mental disorders. Additionally, the Biobank’s dataset is largely self-reported, which could lead to misreporting of diagnoses. In addition, genetic studies and the biobank data set are generally limited to white Europeans.

After concluding that there was no causation, a question remained: why is there so much comorbidity in observational studies? Budu-Aggrey attributed this to confounding factors. “Socio-economic status, level of education and smoking are examples of confounding factors related to both mental disorders and allergic diseases,” she said.

The study provides yet another example of the age-old axiom: Correlation is not causation.

The study was funded by the UK’s Medical Research Council, the European Research Council, and the National Institute for Health Research Bristol Biomedical Research Center, among others. Budu-Aggrey and Burgess do not report any relevant financial relationship.

Allergy Clin Exp. Published online October 6, 2021. Full Text

Miriam Davis, PhD, is an award-winning freelance medical writer who has written over 1,000 articles over a 25-year career.

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