Address correspondence to Maya K. Nanda, MD, MSc, Division of Asthma, Allergy, and Immunology, Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108. E-mail: moc.liamg@alawispaladnan.ayam

Accepted 2015 Oct 22.

Abstract

BACKGROUND AND OBJECTIVES:

The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years.

METHODS:

Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates.

RESULTS:

The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8–5.8), anxiety (aOR: 2.0; 95% CI: 1.2–3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7–6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2–6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7–7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0–9.2) at age 4 had dose-dependent associations with internalizing scores.

CONCLUSIONS:

Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores.

Abstract

What’s Known on This Subject:

Allergic diseases in childhood have been associated with internalizing disorders, including anxiety and depression, but this is not well characterized in longitudinal studies and the effect of multiple allergic diseases on this relationship is unknown.

What This Study Adds:

Young children with allergic rhinitis or allergic persistent wheezing have significantly higher internalizing behavior scores in the school-age years. There is a dose-dependent relationship between multiple allergic diseases in early childhood with internalizing, anxiety, and depression scores in later years.

Up to one-quarter of children <18 years will develop a mental health disorder.¹4 Within the spectrum of mental health disorders, anxiety and depressive disorders are classified under the broader category of internalizing behaviors⁵7 and refer to symptoms that are internally focused including anxiety, phobias, and depressive mood.⁸9 The prevalence of depressive and anxiety disorders in children ages 6 to 19 years has been estimated to range from ∼4% to 8%,¹⁰ and these disorders in childhood have been associated with later mental and behavioral problems,⁸1112 chronic health problems,⁸1314 and high-risk health behaviors.⁴ The association between allergic diseases,¹⁵17 such as allergic rhinitis,¹⁸19 asthma,²⁰21 food allergy,²² and atopic dermatitis,²³24 with internalizing disorders has been shown; however, whereas many of these studies²⁵ used validated measures, few studies have been able to evaluate the relationship longitudinally. In addition, no previous study has extensively evaluated whether there is a dose-dependent relationship between multiple comorbid allergic diseases and the development of internalizing behaviors.

The prevalence of allergic diseases varies based on the population studied; in American children, asthma prevalence has increased to 9.5%,²⁶ food allergy prevalence has increased to 8%,²⁷ allergic rhinitis affects up to 20% of children,²⁸ and atopic dermatitis affects 10% to 20% of children.²⁹ In a German high-risk birth cohort, the prevalence of children with 3 allergic diseases (asthma, eczema, and allergic rhinitis) was 12.2%,³⁰ although the worldwide prevalence for having all 3 allergic diseases was only 1.2%.³¹ Risk factors for allergic diseases and multiple allergic diseases include male gender, parental history of allergies, and socioeconomic status. The increased rates of anxiety and depression in children with allergic diseases have been hypothesized to be due to behavioral modification, meaning that the child’s attitude toward his or her allergies may affect his or her psychological adjustment as seen in other chronic diseases.²²32 Other hypotheses for the increased rates include an underlying biological mechanism that relates to hypersensitivity responses activating cortisol release versus direct effect of T helper 2 cytokines, both of which may alter serotonin release in the prefrontal cortex.³³35

The objective of this study was to investigate the association between well-defined allergic disease phenotypes in childhood and validated measures of internalizing behaviors. Our primary a priori hypothesis was that children with allergic disease at age 4 years, including allergic rhinitis, allergic persistent wheezing, and atopic dermatitis, are at significantly increased risk of internalizing behaviors, including anxiety and depression, at age 7 years. We also a priori hypothesized children with multiple allergic diseases at age 4 years will have increased risk of internalizing behaviors at age 7 years. As exploratory analyses, we determined whether food or aeroallergen sensitization without symptoms in early childhood is significantly associated with internalizing behaviors at age 7 years.

Data are presented as n (%). P values were calculated by using Pearson’s χ^{. *p < .05.}

Covariates include gender, parental asthma, maternal education, BMI, and sleep disturbance. *P < .05, ^P < .001. SPT, skin prick test.

Acknowledgments

We thank Ms Shawna Hottinger, MS, for her revisions, Mr Jeff Burkle, BS, for his expertise in the data set, and Dr Kimberly Yolton, PhD, for her careful review of the manuscript. We thank the CCAAPS participating families for their time and effort in participating in this study. We also thank Dr Simret Nanda, MD, for her informal consultations on the clinical psychiatric implications, and Mr Purvin Lapsiwala, MBA, for his endless support.

Acknowledgments

Glossary

ADHD	attention-deficit/hyperactivity disorder
aOR	adjusted odds ratio
BASC-2	Behavioral Assessment System for Children, Second Edition
CCAAPS	Cincinnati Childhood Allergy and Air Pollution Study
CI	confidence interval
ISAAC	International Study of Asthma and Allergies in Childhood
OR	odds ratio
SPT	skin-prick test

Glossary

Footnotes

Contributed by

Dr Nanda conceptualized and designed the study, performed statistical analysis, drafted the initial manuscript, and made multiple edits to develop the final manuscript as submitted; Drs Ryan and Newman helped conceptualized and design the study and reviewed and revised the manuscript; Drs LeMasters, Bernstein, Khurana-Hershey, and Lockey designed the initial cohort study, coordinated and supervised data collection, and critically reviewed the manuscript; Dr Levin carried out initial statistical analyses, oversaw the analyses conducted by Dr Nanda, and critically reviewed the manuscript; Drs Assa’ad and Rothenberg aided Dr Nanda in design of the study and interpretation of data and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases grant T32 AI060515 and the National Institute of Environmental Health Sciences grants R01 ES019890 and R01ES11170. This publication was supported by an Institutional Clinical and Translational Science Award, NIH/NCRR 5UL1RR026314. Funded by the National Institutes of Health (NIH).

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

All or portions of this article were or will be submitted as a thesis in partial fulfillment of requirements for a Master of Science degree.

Footnotes

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