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2 Oct 2021

Du Rietz E et al. Lancet Psychiatry 2021; 8: 774-783

There is limited knowledge on physical conditions in ADHD, particularly in older adults; however, emerging evidence suggests increased risk of several physical health conditions in people with ADHD (Zhang et al, 2021). This study aimed to investigate the phenotypic and aetiological associations between ADHD and a range of physical health conditions across adulthood. It also examined the extent to which observed associations are primarily genetic or environmental in origin, by estimating the contributions to the associations.

A register study of the Population and Multi-Generation Registers was conducted in Sweden to identify full-sibling and maternal half-sibling pairs born between January 1932 and December 1995. Individuals who died or emigrated before January 2005 were excluded and full-siblings who were not twins and did not have half-siblings were included. International Classification of Diseases diagnoses were obtained from the National Patient Register and were extracted for physical conditions* when individuals were aged ≥18 years and from inpatient (recorded 1973–2013) and outpatient (recorded 2001–2013) services. All diagnoses were categorised as either ‘lifetime presence’ or ‘absence’. Logistic regression models were used to estimate the associations between ADHD and 35 physical conditions in individuals and across sibling pairs, and quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.

A total of 4,789,799 individuals were identified (4,176,415 full-siblings and 613,384 maternal half-siblings; 688,937 individuals were excluded), which included 2,449,146 (51%) men and 2,340,653 (49%) women, with a mean age at end of follow-up of 47 years (range 18–81) and a mean birth year of 1966. There was an overall trend of higher prevalence of ADHD and other conditions in half-siblings compared with full-siblings. Individuals with ADHD had significantly increased risk of all physical conditions except rheumatoid arthritis, after adjusting for sex and birth year, compared with individuals without ADHD (all p values <0.007). The strongest associations with ADHD were with alcohol-related liver disease (odds ratio [OR] 4.70; 95% confidence interval [CI] 3.96–5.58]), sleep disorders (OR 4.62; 95% CI 4.43–4·82), chronic obstructive pulmonary disease (OR 3.24; 95% CI 2.96–3.56), epilepsy (OR 2.99; 95% CI 2.82–3.16), fatty liver disease (OR 2.94; 95% CI 2.38–3.63) and obesity (OR 2.67; 95% CI 2.55–2.78). Full-siblings of individuals with ADHD had significantly increased risk for most physical conditions and these associations were generally reduced in maternal half-siblings.

The analyses of the eight broader disease groups revealed that the strongest associations with ADHD were with nervous system (OR 3.27; 95% CI 3.17–3.37), respiratory (OR 2.49; 95% CI 2.40–2.59), musculoskeletal (OR 2.03; 95% CI 1.97–2.09) and metabolic (OR 2.02; 95% CI 1.96–2.09) diseases. These associations were significantly stronger between full-siblings than between maternal half-siblings (p values <0.007). Although sex-stratified analyses indicated similar patterns of results in men and women, it was also revealed that the increased risk of atrial fibrillation, urolithiasis, sleep disorders and asthma in women with ADHD was significantly higher than in men with ADHD (non-overlapping CIs), whereas the increased risk of thyroid disorder in women with ADHD was lower than in men with ADHD. Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60–69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors. In the quantitative genetic analyses, the strongest phenotypic correlation was observed between ADHD and nervous system disorders (OR 0.23 [95% CI 0.23–0.24]. In this case, the correlation was explained by genetic factors (28%; 95% CI 7–49), shared environmental factors (13%; 95% CI 3–22), and non-shared environmental factors (59%; 95% CI 47–71). Significant phenotypic correlations were also observed between ADHD and metabolic, respiratory and musculoskeletal disease groups (0.14–0.16), for which genetic factors explained 60–69% of correlations and non-shared environmental factors explained the remainder.

There were several limitations associated with this study. Firstly, it relied upon register-based diagnoses which means the findings are only reflective of those diagnosed, as opposed to individuals who do not receive or seek healthcare support. Furthermore, the effect of ADHD medication on physical conditions was not investigated due to an absence of information on medication before 2005. There were variations in follow-up length and age at follow-up between individuals in the study, which may have introduced bias. A form of potential outcome misclassification bias in this study was the incomplete coverage by the register before the changes in diagnostic practices for ADHD were made, which may have biased estimates towards the null. In addition to this, the findings of this study may not be generalisable for any individuals who had incomplete data. ADHD may have been misclassified before the disorder became commonly diagnosed in Sweden, potentially diluting the estimated associations. Finally, associations between ADHD and late-onset conditions may have been underestimated due to individuals who died prematurely.

The authors concluded that this study showed that adults with ADHD are at increased risk of a range of physical conditions, including circulatory, metabolic, gastrointestinal, genitourinary, musculoskeletal, nervous system, respiratory and skin diseases. They noted that most physical conditions showed familial associations with ADHD and highlighted the possibility of long-term consequences associated with age-related diseases. The need for rigorous medical assessment and care in adults with ADHD was also highlighted. Finally, the authors noted that the findings from this study could, in their opinion, guide future research that aims to identify shared biological mechanisms or modifiable risk factors that contribute to risk of physical conditions in individuals with ADHD.

Read more about the associations between ADHD and physical conditions here

 

*Physical conditions include circulatory system, endocrine or metabolic, gastrointestinal, genitourinary, musculoskeletal, nervous system, respiratory and skin conditions

Disclaimer: The views expressed here are the views of the author(s) and not those of Takeda.

Du Rietz E, Brikell I, Butwicka A, at al.  Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study. Lancet Psychiatry 2021; 8: 774-783.

Zhang L, Reif A, Du Rietz E, et al. Comedication and polypharmacy with ADHD medication in adults: a Swedish nationwide study. J Atten Disord 2021; 25: 1519-1528.

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