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Nitrogen Dioxide Linked to Higher ADHD Risk: Insights from a Massive South Korean Study

A landmark nationwide study from South Korea has uncovered a significant link between prenatal exposure to air pollution — specifically nitrogen dioxide (NO2) — and an increased risk of ADHD in children. 

While researchers have long suspected that air pollutants interfere with fetal brain development through inflammation and oxidative stress, this study is one of the largest and most comprehensive of its kind, following nearly 1.5 million births for up to 13 years. 

Why South Korea? 

South Korea provided a unique countrywide “laboratory” for this research due to two key infrastructure strengths: 

  • Universal Health Data: A national insurance database that tracks the health outcomes of the entire population. 
  • Granular Air Monitoring: A network of 642 monitoring stations that allowed researchers to precisely estimate what pollutants mothers were breathing based on their postal codes. 

Key Findings: The “Smoking Gun” of NO2 

While the study looked at several pollutants, nitrogen dioxide — a byproduct of fossil fuel combustion in cars and power plants — emerged as the primary concern. 

Pollutant 

Association with ADHD Risk 

Nitrogen Dioxide (NO2) 

Strongest Link: Every 1-ppb (part-per-billion) increase in exposure linked to a 22% rise in risk. 

Sulfur Dioxide (SO2) 

Minimal Link: Only a slight 4% increase per ppb. 

Ozone (O3) carbon monoxide (CO), & particulates 

No significant association was found. 

The scale of the NO2 risk is particularly striking. Over the typical range of exposure levels found in the study (an interquartile range of 13 ppb), the data suggest a threefold increase in ADHD risk for children in the highest-exposure groups compared to the lowest. 

Accounting for Other Factors 

To ensure the results weren’t skewed by other variables, the researchers controlled for a wide range of confounders including: 

  • Socioeconomic and employment status. 
  • Maternal age and baseline health. 
  • The child’s sex. 
  • The presence of 14 different medical conditions around childbirth. 

The authors emphasized the strong association between maternal nitrogen dioxide exposure and ADHD, while also noting the small but significant association with sulfur dioxide.  

The Take-Away: A New Frontier for Public Health 

Historically, air quality laws have been designed to protect our lungs and hearts. However, this study adds to a growing body of evidence suggesting that the brain is likewise vulnerable. 

In a commentary on the findings, expert George Ayoub argued that “neurodevelopment should be explicitly considered” when governments perform cost-benefit analyses on air quality regulation.  My view is a bit different.  The association is intriguing but the study does not establish cause and effect.  Many statistically significant environmental risk associations for neurodevelopmental disorders have disappeared after controlling for maternal risk for ADHD.  I hope this research team will do those analyses if feasible.

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ADHD May Be Underdiagnosed Based on Sociodemographics

ADHD is underdiagnosed, to varying degrees, among adults of different ethnicities, ages, and education levels in the U.S.

ADHD is underdiagnosed and most cases of ADHD in adults are not being diagnosed by clinicians.

A cohort study looked at over five million adults and over 850,000 children between the ages of five and eleven who received care at Kaiser Permanente Northern California during the ten-year period from the beginning of 2007 through the end of 2016. At any given time, KPNC serves roughly four million persons. It is representative of the population of the region, except for the highest and lowest income strata.

ADHD Diagnosis Rates:

  • Adults: Diagnosis rates rose from 0.43% in 2007 to 0.96% in 2016.
  • Children: Diagnosis rates went up from 2.96% to 3.74%, nearly four times higher than in adults.

Diagnosis Rates by Ethnicity:

  • Non-Hispanic whites had the highest adult diagnosis rates, increasing from 0.67% to 1.42%.
  • American Indian/Alaska Native (AIAN): Rates grew from 0.56% to 1.14%.
  • Black and Hispanic adults had similar rates: Black adults increased from 0.22% to 0.69%, and Hispanic adults rose from 0.25% to 0.65%.
  • Asian adults had the lowest rates (0.11% to 0.35%), followed by Native Hawaiian/Pacific Islanders (0.11% to 0.39%).

ADHD Diagnosis and Age:

The likelihood of being diagnosed with ADHD dropped sharply with age.

(When compared to 18-24-year-olds):

  • 25-34-year-olds were 16% less likely.
  • 35-44-year-olds were 33% less likely.
  • 45-54-year-olds were less than half as likely.
  • 55-64-year-olds were less than a quarter as likely.
  • Adults over 65 were about 5% as likely.

This matches findings from other studies showing that ADHD diagnoses become less common with age.

Other Factors:

  • Adults with higher education levels were twice as likely to be diagnosed as those with less education.
  • Household income had little effect on diagnosis rates.
  • Women were slightly less likely to be diagnosed than men.

ADHD and Comorbidity:

Adults with ADHD were more likely to have other mental health conditions:

  • Eating disorders: 5 times more likely.
  • Bipolar disorder or depression: Over 4 times more likely.
  • Anxiety: More than twice as likely.
  • Substance abuse: Slightly more likely.

Key Findings:
  1. Rising ADHD Diagnosis Rates: The increase in diagnoses may be due to better recognition of ADHD by doctors and greater public awareness during the study period.
  2. Differences by Ethnicity: The differences in diagnosis rates by ethnicity could be related to access to healthcare, cultural attitudes toward mental health, or even attempts to obtain ADHD medications for non-medical reasons, which may be more common among white patients.
Conclusion:

The authors speculate that rising rates of diagnosis “could reflect increasing recognition of ADHD in adults by physicians and other clinicians as well as growing public awareness of ADHD during the decade under study.” Turning to the notable differences by ethnicity, they note, “Racial/ethnic differences could also reflect differential rates of treatment-seeking or access to care. … Racial/ethnic background is known to play an important role in opinions on mental health services, health care utilization, and physician preferences. In addition, rates of diagnosis- seeking to obtain stimulant medication for non-medical use may be more common among white vs nonwhite patients.” They conclude, “greater consideration must be placed on cultural influences on health care seeking and delivery, along with an increased understanding of the various social, psychological, and biological differences among races/ethnicities as well as culturally sensitive approaches to identify and treat ADHD in the total population.”

The study highlights that many cases of adult ADHD go undiagnosed. Research shows about 3% of adults worldwide have ADHD, but this study found that less than 1% are diagnosed by doctors. This points to the need for better training for clinicians to recognize, diagnose, and treat ADHD in adults. It also emphasizes the importance of understanding cultural factors that affect how people seek and receive care.

April 12, 2022
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Daytime Sleepiness, Cognitive Function, and Adult ADHD

What's The Relationship Between Daytime Sleepiness and Cognitive Functioning in Adults with ADHD?

Sleep disorders are one of the most commonly self-reported comorbidities of adults with ADHD, affecting 50 to 70 percent of them. A team of British researchers set out to see whether this association could be further confirmed with objective sleep measures, using cognitive function tests and electroencephalography (EEG).

Measured as theta/beta ratio, EEG slowing is a widely used indicator in ADHD research. While it occurs normally in non-ADHD adults at the conclusion of a day, during the day it signals excessive sleepiness, whether from obstructive sleep apnea or neurodegenerative and neurodevelopmental disorders. Coffee reverses EEG slowing, as do ADHD stimulant medications.

Study participants were either on stable treatment with ADHD medication (stimulant or non-stimulant medication) or on no medication. Participants had to refrain from taking any stimulant medications for at least 48 hours prior to taking the tests. Persons with IQ below 80 or with recurrent depression or undergoing a depressive episode were excluded.

The team administered a cognitive function test, The Sustained Attention to Response Task (SART). Observers rated on-task sleepiness using videos from the cognitive testing sessions. They wired participants for EEG monitoring.

Observer-rated sleepiness was found to be moderately higher in the ADHD group than in controls. Although sleep quality was slightly lower in the sleepy group than in the ADHD group, and symptom severity slightly greater in the ADHD group than the sleepy group, neither difference was statistically significant, indicating extensive overlap.

Omission errors in the SART were strongly correlated with sleepiness level, and the strength of this correlation was independent of ADHD symptom severity. EEG slowing in all regions of the brain was more than 50 percent higher in the ADHD group than in the control group and was highest in the frontal cortex.

Treating the sleepy group as a third group, EEG slowing was highest for the ADHD group, followed closely by the sleepy group, and more distantly by the neurotypical group. The gaps between the ADHD and sleepy groups on the one hand, and the neurotypical group on the other, were both large and statistically significant, whereas the gap between the ADHD and sleepy groups was not. EEG slowing was both a significant predictor of ADHD and of ADHD symptom severity.

The authors concluded, These findings indicate that the cognitive performance deficits routinely attributed to ADHD are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity.  we would like to propose a simple working hypothesis that daytime sleepiness plays a major role in cognitive functioning of adults with ADHD. As adults with ADHD are more severely sleep deprived compared to neurotypical control subjects and are more vulnerable to sleep deprivation, in various neurocognitive tasks they should manifest larger sleepiness-related reductions in cognitive performance. One clear testable prediction of the working hypothesis would be that carefully controlling for sleepiness, time of day, and/or individual circadian rhythms would result in a substantial reduction in the neurocognitive deficits in replications of classic ADHD studies.

January 31, 2021
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