Asthmahas long been associated with lower quality of life as a result of reducedactivity and increased psychological stress.1 Indeed, any identifiedlinks between asthma and mental health have primarily been unidirectional, withasthma leading to mental illness. However, recent studies have revealed geneticlinks between asthma and mental health.

Research suggests that people with asthma are more likely to develop mental health problems compared with the general population. In a study conducted with school children, the prevalence of diagnosed mental health conditions among those with asthma was 8.2%, which was nearly double the prevalence among those without asthma (4.8%).2 Another study comprising adults showed that mood disorders were strongly associated with allergic asthma, late-onset asthma, and infection-based asthma.3 In addition, researchers discovered that mental health care services were more likely to be used by people after a diagnosis of asthma.4

Morestudies are underway to investigate the bidirectional connection between asthmaand mental health. One study has linked asthma severity to lifetime and currentanxiety, with asthma preceding anxiety in 48% of the patients and anxietypreceding asthma in 52% of the patients.5

Thereis growing evidence for the involvement of genetics in this asthma-mentalhealth connection. A Swedish study that identified self-report associationsbetween asthma and major depressive disorder (MDD), anxiety, and neuroticismalso found genetic correlations between asthma and MDD, but not between asthmaand anxiety or neuroticism.6

Anotherstudy, a large-scale genome-wide cross trait analysis, has shown a strongassociation between asthma and 3 mental disorders: attention-deficit/hyperactivitydisorder (ADHD), anxiety disorder, and MDD.7 A total of 7 loci werefound to be jointly associated with asthma and ADHD; 1 loci with asthma andanxiety disorder; and 10 loci with asthma and MDD.

Accordingto Dr Zhaozhong Zhu, a lead researcher, Mendelianrandomization a method of using measured variation in genes of known function was used to inferputative causal relationshipsbetween asthma and mental health disorders in both directions, with our resultssuggesting that ADHD and MDD might increase the risk for asthma. Dr Zhu makesit clear that the mechanismof the association is unknown. Thecausal relationship found in the study is only based on genetic variables, heexplains. The epidemiologic association includes 2 key components: genetics(ie, genes and biological mechanisms) and environment (ie, social factors,exposure to certain conditions [asthma], and medication use).

The study findings indicate geneticcausality in the direction of mental illness causing asthma. However, theenvironmental causality is in the reverse direction and outweighs the geneticcausality; thus, the overall epidemiologic causality is in the direction ofasthma causing mental health disorders.

Compared with other mentaldisorders, depression appears to have the strongest link to asthma. In additionto the 10 loci found by Dr Zhu and his team, a single-nucleotide polymorphism(SNP) known as rs4672619, located on the Erb-B2 receptor tyrosine kinase 4gene, has been implicated in the comorbidity of depression and asthma.8The researchers who discovered the SNP evaluated the relationship between thedepressive status of the individuals and the rs4672619 genotypes on asthmasymptom severity. In childhood asthmatics, severe depression was related toless severe asthma symptoms, while in those with heterozygous and homozygousvariant alleles, severe depression was related to more severe asthma symptoms.

In elderly patients with asthma, thereverse was true. Those with the homozygous reference allele had a positivecorrelation between depression and asthma symptom severity, while a negativecorrelation was seen in those with heterozygous and homozygous variant alleles.Further studies on the relationship between the conditions could lead to thedevelopment of personalized therapies for the simultaneous treatment of bothconditions.

Few studies have established thegenetic link between asthma and anxiety. A Chinese investigation demonstratedthe effect of interactions between serotonin transporter (5-HTT), brain-derivedneurotrophic factor (BDNF), and the neuropeptide S receptor 1 gene, NPSR1-AS1 polymorphisms on anxiety and depression.9Interactions between 5-HTT (LL alleles) and BDNF (A+ allele) led to anincreased anxiety score, while interactions between BDNF (A+, GG) and NPSR1(AA, T+) increased the depression score.

While the genetic link betweenasthma and ADHD was strongly revealed in Dr Zhus study, most other studieshave been anecdotal. A large Swedish study found a significant associationbetween asthma and ADHD, even after removing possible confounding variables.10It has been hypothesized that because asthma and ADHD both have large geneticcomponents, people who are genetically susceptible to one condition may besusceptible to the other.11

Studying genetic variants raises thequestion of whether any genetic links have cross-cultural implications. Whilethe participants in Dr Zhus research were mainly European, Dr Zhu expectsthat, Asthma and mental health disorders should be genetically similar, butnot the same across major populations, such as African American, Hispanic, orAsian. He points out that one of the shared genetic loci between asthma andMDD, the human leukocyte antigen region on chromosome 6, has a pervasivegenetic effect in many diverse populations.

Currently, corticosteroids areconsidered the most effective long-term treatment for asthma. However, chroniccorticosteroid use has been associated with psychosis, depression, anxiety, andmania in people with asthma.12,13 Psychological treatments are being exploredas alternative interventions for asthma and while no psychotherapy has beenscientifically proven to improve asthma and comorbid mental illness, there hasbeen an increased interest in the use of cognitive behavioral therapy.14,15

Understanding the geneticassociation between asthma and mental health creates an opportunity for thedevelopment of more effective drugs and therapeutic approaches that could treatasthma and associated mental health disorders together. In Dr Zhus study, functionalanalysis revealed that the identified variants regulated gene expression intissues of various body systems, including the respiratory and immune system.Thus, further understanding of these variants may lead to treatments thataddress the respiratory and immune system problems often seen in people asthma.

According to Dr Zhu, In the short term,we aim to inform the general population that mental health disorders can haveshared genetic factors with asthma. Therefore, controlling environmentalfactors, such as eating healthy, enjoying a happy life, and being careful withthe potential adverse effects of medication, will help to prevent asthma andmental health disorders. In the long term, with more mechanistic studies, wehope to provide direction in the development of drugs for preventing andtreating both conditions at the same time.

References

1. American Academy of Allergy Asthma & Immunology. Increased mental health care use in adults after asthma diagnosis. http://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/mental-health. April 7,2017. Accessed November 5, 2019.

2. Lawson J, Rennie D, Dyck R, Cockcroft D, Afanasieva A. The relationship between childhood asthma and mental health conditions.Eur Respir J. 2017;50(suppl 61):PA595.

3. Labor M, Labor S, Juri I, Fijako V, Grle S, Plavec D. Mood disorders in adult asthma phenotypes.J Asthma. 2017;55(1):57-65.

4. To T, Ryckman K, Zhu J, et al. Mental Health Services Claims and Adult Onset Asthma in Ontario, Canada.J Allergy Clin Immunol Pract. 2017;5(5):1388-1393.e3.

5. Del Giacco S, Cappai A, Gambula L, et al. The asthma-anxiety connection.Respir Med. 2016;120:44-53.

6. Lehto K, Pedersen N, Almqvist C, Lu Y, Brew B. Asthma and affective traits in adults: a genetically informative study.Eur Respir J. 2019;53(5):1802142.

7. Zhu Z, Zhu X, Liu C et al. Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis [published online October 17, 2019].Eur Respir J. doi:10.1183.13993003.01507-2019

8. Park H, Song W, Cho S, et al. Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics. Exp Mol Med. 2018;50(7):77.

9. Yang Y, Zhao M, Zhang Y, Shen X, Yuan Y. Correlation of 5-HTT, BDNF and NPSR1 gene polymorphisms with anxiety and depression in asthmatic patients. Int J Mol Med. 2016;38(1):65-74.

10. Cortese S, Sun S, Zhang J, et al. Association between attention deficit hyperactivity disorder and asthma: a systematic review and meta-analysis and a Swedish population-based study. Lancet Psychiatry. 2018;5(9):717-726.

11. Rapaport L. Links seen between asthma and ADHD. Reuters website. http://www.reuters.com/article/us-health-adhd-asthma/links-seen-between-asthma-and-adhd-idUSKBN1L12FZ. August 15, 2018. Accessed November 14, 2019.

12. Kewalramani A, Bollinger M, Postolache T. Asthma and mood disorders.Int J Child Health Hum Dev. 2008;1(2):115-123.

13. University of Newcastle Australia. Severe Asthma Toolkit. Asthma and Mental Health. https://toolkit.severeasthma.org.au/living-severe-asthma/mental-emotional-health/. Updated February 12, 2019. Accessed November 5, 2019.

14. Kew K, Nashed M, Dulay V, Yorke J. Cognitive behavioural therapy (CBT) for adults and adolescents with asthma.Cochrane Database Syst Rev. 2016;9:CD011818.2

15. Pateraki E, Morris P. Effectiveness of cognitive behavioural therapy in reducing anxiety in adults and children with asthma: a systematic review.J Asthma. 2018;55(5):532-554.

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The Genetic Link Between Asthma and Mental Health - Pulmonology Advisor