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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.
Counting umbilical cord vessels is standard in prenatal ultrasounds and confirmed at birth. Single umbilical artery (SUA) occurs in about 1 in 200 cases, with roughly 10% associated with anomalies, including central nervous system defects. Isolated SUA (iSUA) means one artery is missing without other structural issues.
Research on SUA, especially isolated iSUA, and childhood neurodevelopmental disorders (NDD) is limited and inconclusive. iSUA is linked to preterm birth and small-for-gestational age (SGA), both of which are NDD risk factors.
This Norwegian nationwide population study aimed to assess NDD risk in children with iSUA at birth, the influence of sex, and how preterm birth and SGA mediate this relationship.
The nation’s universal single-payer health insurance and comprehensive population registries made it possible to analyze all 858,397 single births occurring from 1999 to 2013, with follow-up continuing through 2019. Among these cases, 3,532 involved iSUA.
After adjusting for confounders such as parental age, education, and maternal health factors, no overall link was found between iSUA and later ADHD diagnosis. However, females with iSUA had about a 40% higher risk of subsequent ADHD compared to those without iSUA, even after adjustment.
The authors concluded, “The present study indicates that iSUA is weakly associated with ID [intellectual disability] and ADHD, and these associations are influenced by sex. This association is mediated negligibly through preterm birth and SGA. The associations were not clinically significant, and the absence of associations of iSUA with other NDD is reassuring. This finding can be useful in the counseling of expectant parents of fetuses diagnosed with iSUA.”
Refractive errors, such as myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (distorted vision due to irregular curvature of the eye or lens), are common worldwide. These conditions affect 12%, 5%, and 15% of children, and rise significantly in adults to 26.5%, 31%, and 40%. Additionally, strabismus (misalignment of the eyes) and amblyopia (reduced vision in one eye from uneven image formation, often linked to strabismus) occur globally at rates of 2% and 1.4%, respectively.
Visual impairment can affect children’s concentration in school, and studies suggest a link between eye disorders and ADHD.
To investigate this relationship, two researchers – one based in the US and the other in Israel –carried out a nationwide retrospective cohort study using electronic medical records of all insured individuals aged 5 to 30 who were part of Maccabi Health Services, Israel’s second largest health maintenance organization, between 2010 and 2022.
Of over 1.6 million insured members (2010–2020), inclusion/exclusion criteria and propensity score matching for age and sex were applied, along with a one-year wash-out period between the first eye diagnosis and ADHD diagnosis. In total, 221,707 cases were matched with controls without eye disorders at a 1:2 ratio, resulting in a cohort of 665,121 participants.
Overall, those with any previous eye diagnosis were 40% more likely to have a subsequent ADHD diagnosis. This was slightly higher for females (45%) than for males (35%). It was also slightly higher for children and adolescents (42%) than for adults (37%).
More specifically:
The authors concluded that eye disorders are associated with ADHD. They noted these associations were more marked in females and children and adolescents, although, as noted above, those differences were small. They recommended that primary care providers and neurologists consider risk stratification for early screening, and that ophthalmologists refer high-risk patients for ADHD evaluation.
Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, are often prescribed during pregnancy to treat heartburn and gastroesophageal reflux disease.
Research shows changes in the gut microbiome can negatively affect neurodevelopment. Since acid-suppressive medications alter gut microbiota, maternal use during pregnancy may impact offspring’s neurodevelopment. Because PPIs and H2 receptor antagonists readily cross the placental barrier, they could potentially influence fetal neurodevelopment.
The link between prenatal exposure to acid-suppressive medications and major neuropsychiatric disorders is not well understood. With the use of these medications during pregnancy rising, it is important to assess their impact on children's long-term neurodevelopment. This study examined whether maternal use of acid-suppressive drugs is associated with increased risk of neuropsychiatric disorders in children, using a large, nationwide birth cohort from South Korea.
South Korea operates a single-payer health insurance system, providing coverage for over 97% of its citizens. The National Health Insurance Service (NHIS) maintains a comprehensive database with sociodemographic details, medical diagnoses, procedures, prescriptions, health examinations, and vital statistics for all insured individuals.
A Korean research team analyzed data from over three million mother-child pairs (2010–2017) to assess the risks of prenatal exposure to acid-suppressing medications. They applied propensity scoring to adjust for maternal age, number of children, medical history, and outpatient visits before pregnancy, to minimize confounding factors. That narrowed the cohort to just over 800,000 pairs, with half in the exposed group.
With these adjustments, prenatal exposure to acid-suppressing medications was associated with 14% greater likelihood of being subsequently diagnosed with ADHD.
Yet, when 151,737 exposed births were compared to the same number of sibling controls, no association was found between prenatal exposure and subsequent ADHD, which suggests unaccounted familial and genetic factors influenced the preceding results.
The Take-Away:
Evidence of these medications negatively affecting pregnancies is mixed, mostly observational, and generally reassuring when these medications are used appropriately. Untreated GERD and gastritis, however, have known risks and associations with the development of various cancers. With no evidence of an association with ADHD (or for that matter any other neuropsychiatric disorder), there is no current evidence-based reason for expectant mothers to discontinue use of acid-suppressing medications.
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