October 16, 2021
What are the links between ADHD and physical ailments in adults? And, where such links exist, how can we tease out where they are due to genetics, shared environment, or unshared environmental influences?
An international research team used the Swedish population and health registers to explore these links in an entire national population. They were able to do this because Sweden has a single-payer national health insurance system, cross-referenced with the population and other national registries through personal identification numbers.
This study identified full-sibling and maternal half-sibling pairs born from 1932 through 1995, through the Population and Multi-Generation Registers. This yielded a total of 4,789,799 individuals - consisting of 3,819,207 full-sibling pairs and 469,244 maternal half-sibling pairs, and 1,841,303family clusters (siblings, parents, cousins, spouses). Roughly half were men, the other half women.
After adjusting for sex and birth year, those with ADHD were at significantly higher risk of a wide range of physical ailments, when compared with individuals without ADHD:
· Over four times as likely to have sleep disorders or develop alcohol-related liver disease;
· Roughly three times as likely to develop the chronic obstructive pulmonary disease, epilepsy, and fatty liver disease;
· Over two and a half times more likely to become obese.
Overall, ADHD was significantly associated with 34 of the 35 physical diseases studied, rheumatoid arthritis being the only exception.
Comparing men with women, women with ADHD were at significantly greater risk of atrial fibrillation, urolithiasis, sleep disorders, and asthma than men with ADHD. Conversely, men with ADHD faced a greater risk of thyroid disorder than women with ADHD.
Between-sibling analyses showed that full siblings of individuals with ADHD were at significantly increased risk for 27 of the 35 physical ailments, suggesting that shared familial factors contributed to the co-occurrence of the conditions. This remained true even after adjusting for the occurrence of ADHD in full siblings.
These associations were generally reduced in maternal half-siblings of individuals with ADHD. The associations between full-siblings were significantly stronger than between maternal half-siblings for type 1 diabetes, obesity, kidney infections, back or spine pain, migraine, sleep disorders, asthma, and chronic obstructive pulmonary disease.
Keep in mind that full-siblings on average share half of their genes, whereas maternal half-siblings share only a quarter of their genes. Maternal (as opposed to paternal) half-siblings were chosen as a basis for comparison because they are typically brought up together in the same family setting, and thus are similar to full-siblings in having a shared family environment. Reduced risk in maternal half-siblings would therefore signal a genetic component to the risk.
Given that ADHD is itself a nervous system disorder, it is unsurprising that it correlated most strongly with other nervous system disorders, with a medium effect size (r=.23). Genetic factors explained over a quarter of the correlation, shared environmental factors over a seventh, and non-shared environmental factors the other three-fifths. The latter could point to environmental risk factors that influence both ADHD and nervous system diseases.
Small-to-medium correlations were found with metabolic, respiratory, and musculoskeletal disease groups, with genetic factors explaining roughly two-thirds of the correlation, and non-shared environmental factors most of the rest.
The authors concluded that "adults with ADHD are at increased risk of a range of physical conditions, across circulatory, metabolic, gastrointestinal, genitourinary, musculoskeletal, nervous system, respiratory, and skin diseases. Most physical conditions showed familial associations with ADHD (mainly from genetic factors). Our findings highlight the need for rigorous medical assessment and care in adult patients with ADHD, and suggest long-term consequences of age-related diseases."
Ebba Du Rietz, Isabell Brickell, AgnieszkaButwicka, Marica Leone, Zheng Chang, Samuele Cortese, Brian M D'Onofrio, Catharina A Hartman, Paul Lichtenstein, Stephen V Faraone, Ralf Kuja-Halkola, Henrik Larsson, "Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study," Lancet Psychiatry (2021), vol. 8, issue 9, 774-783, published online, https://doi.org/10.1016/S2215-0366(21)00171-1.
A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD).
A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by:
Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings.
The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding.
Almost 186,000 of these children were exposed to acetaminophen during pregnancy.
After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed.
However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication. High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage.
Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.
The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.”
Antipsychotic medications are used to treat a variety of psychiatric disorders, including schizophrenia, bipolar disorder, sleeping problems, major depression, and severe anxiety.
Untreated maternal mental illness is associated with poor health outcomes for both mothers and their offspring. On the other hand, one must guard against any potential direct harms of medications on development – including neurological development – of the fetus.
Because prenatal use of antipsychotics is infrequent, previous observational studies have suffered from small sample sizes that have not enabled precise and reliable assessment of risk. The clinical decision about whether to continue antipsychotic treatment in patients who become pregnant has therefore remained inconclusive.
In search of more reliable guidance, an international study team conducted a systematic search of the peer-reviewed medical literature to perform the first meta-analysis on this topic.
They evaluated study quality and only included studies rated “good” or better.
Identification of ADHD was determined by clinical diagnosis.
Meta-analysis of four studies encompassing over eight million participants found a slight association. Children exposed to maternal antipsychotics during pregnancy were 11% more likely to be diagnosed with ADHD subsequently.
But even in observational studies with millions of participants, such associations – especially when slight to begin with – could be due to unmeasured confounders.
The team therefore compared children with gestational exposure to siblings from the same mother who were not exposed, to address shared genetic and social factors at the family level.
Meta-analysis of two population-based sibling-matched studies with a combined total of over 4.6 million participants in Denmark, Norway, Sweden, Finland, Iceland, and Hong Kong found no significant association between gestational exposure to antipsychotic medications and subsequent diagnosis of ADHD.
The team concluded, “Our systematic review and meta-analysis of observational studies indicates that the heightened risks of ADHD and ASD observed in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relation to the antipsychotic itself.”
Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time.
An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107 children who have been followed up every two years since birth.
The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.
Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year.
The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ).
Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10.
With a diagnosis of ADHD at age 10 and all other factors held constant:
Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect.
Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes.
The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.”
_logo%201.svg)
