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December 31, 2021
Certain air pollutants can produce free radicals and inflammatory cytokines that can penetrate the central nervous system and affect behavior. Long-term exposure to air pollution has been associated with a higher risk of developing ADHD.
There has, however, been little focus on the short-term effects of exposure. Might there be any correlation between levels of air contaminants and subsequent healthcare visits of adolescents for severe spikes in ADHD symptoms (frequently but not always associated with comorbid conduct disorder, oppositional defiance disorder, or mood disorder), such as extreme hyperactivity, serious rule violations, theft, or aggression to people or animals?
A South Korean (Republic of Korea) research team explored this question through a nationwide cohort study using the database of the National Health Insurance Service, a single-payer system, that covers the entire population.
Using a time-series approach, they compared measured levels of three airborne pollutants - particulate matter with a diameter ≤ 10 μm (PM10), nitrogen oxide (NO2), produced by vehicular traffic, and sulfur dioxide (SO2), produced by manufacturing industries- with healthcare visits with a principal diagnosis of ADHD. They chose these three contaminants because they have been associated with ADHD in long-term studies. What made this approach feasible is that healthcare visits are typically unscheduled in Korea, making it possible to get quick medical attention.
The team divided the country into sixteen regions, looked at boys and girls separately, and also split adolescents into two age groups (10 to 14 years and 15 to 19 years). They estimated region-specific daily concentrations of the three pollutants from 318 government-run monitoring sites, located according to population density and distribution.
The researchers next calculated zero(same day) to five-day lag figures for ADHD-related healthcare visits in each region and ran meta-analyses on the time-series data.
There were 7,200 ADHD-related healthcare visits in the 2013-2015 study period. Major increases in PM10 levels were associated with increased ADHD-related healthcare visits from the day of the spike to three days later, peaking the day after the upturn. Major increases in SO2 levels were associated with increased ADHD-related healthcare visits from one to four days later, peaking the day following the upturn. Major increases in NO2 levels were associated with increased ADHD-related healthcare visits from one to four days later, peaking three days after the spike.
There were no significant differences between male and female adolescents, and between younger and older adolescents.
The strongest increased risk for ADHD-related healthcare visits was for NO2 spikes (up 47 percent), followed by SO2 spikes (up 27 percent), with PM10 spikes coming in last (up 12 percent).
Among the limitations, the authors were unable to evaluate the most hazardous types of particulate emissions, because the smaller-diameter PM2.5 particles (≤2.5 μm) have only been measured partially in South Korea since 2015. On the other hand, they pointed out that this was the first study to investigate associations between short-term air pollution exposure and ADHD-related healthcare visits, and that it included all ADHD-related healthcare visits in South Korea, making the possibility of selection bias negligible. They recommended conducting similar studies on other national populations.
Jiyoon Park, JiHoon Sohn, Sung Joon Cho, Hwa Yeon Seo, Il-Ung Hwang, Yun-Chul Hong, Kyoung-Nam Kim, "Association between short-term air pollution exposure and attention-deficit/hyperactivity disorder-related healthcare visits among adolescents: A nationwide time-series study," Environmental Pollution (2020) 226, https://doi.org/10.1016/j.envpol.2020.115369.
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.
For years, a persistent concern has shadowed the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Does the medication eventually stop working? Patients often report that their symptoms seem to return despite consistent use, leading to "dose escalation" or "medication holidays." A new systematic review from Sam Cortese’s team published in CNS Drugs finally puts these concerns to the test by synthesizing decades of empirical research.
Before diving into the findings, you must understand two often-confused phenomena:
The review analyzed 17 studies covering over 10,000 individuals, and the results provide a much-needed reality check for the clinical community.
The researchers found preliminary evidence that acute tolerance (tachyphylaxis) can occur within a 24-hour window.
The most important finding is that tolerance does not commonly develop to the therapeutic effects of ADHD medication in the long term. In one landmark study following children for up to 10 years, only 2.7% of participants lost their response to methylphenidate without a clear external explanation. Doses, when adjusted for natural body growth, remained remarkably stable over years of treatment.
Consistent with the lack of therapeutic tolerance, the body does not become tolerant to the physical side effects of stimulants. Increases in heart rate and blood pressure typically persist for as long as the medication is taken. This underscores why clinicians must continue monitoring cardiovascular health throughout the entire duration of treatment.
If it’s Not Tolerance, What Is It?
If "tolerance" isn't real, why do some patients feel their medication is failing? The review suggests clinicians look at these alternative explanations:
Why This Matters
These results provide clinicians the confidence to tell patients that their medication is unlikely to "wear out" permanently. Rather than immediately increasing a dose when symptoms flare, the first step should be a "clinical deep dive" into the patient's lifestyle, stress levels, and adherence.
For researchers, the review highlights a major gap: most existing studies are small, dated, or of low quality. There is a dire need for robust, longitudinal studies that track both the brain's response and the patient's environment over several years.
For people with ADHD, while your body might get "used to" the initial "buzz" of a stimulant within hours, its ability to help you focus and manage your life remains remarkably durable over the years.
The Background:
Concerns remain about how ADHD and methylphenidate (MPH) use might affect children's health and growth, and especially how it may affect their adult height. While some studies suggest disrupted growth and a possible biological mechanism, the impact of ADHD prevalence and MPH use is still unclear. Children with ADHD may develop unhealthy habits – irregular eating, low physical activity, and poor sleep – that can contribute to obesity and reduced height. MPH’s appetite-suppressing effect can lead to skipped meals or overeating. Since growth hormone is mainly released during deep sleep, chronic sleep deprivation could plausibly slow growth and impair height development; however, a clear link between ADHD, MPH use, overweight, and shorter stature has never been firmly established.
The Study:
South Korea has a single payer health insurance system that covers more than 97% of its population. A Korean research team used the National Health Insurance Service database to perform a nationwide population study to explore this topic further.
The study involved 34,850 children, of whom 12,866 were diagnosed with ADHD. Of these children, 6,816 (53%) had received methylphenidate treatment, while 6,050 (47%) had not. Each patient with ADHD was precisely matched 1:1 by age, sex, and income level to a control participant without ADHD. The sex ratio was comparable in all groups.The team used Body Mass Index (BMI) as an indicator of overweight and obesity.
The Results:
The researchers found that being diagnosed with ADHD was associated with 50% greater odds of being overweight or obese as young adults, and over 70% greater odds of severe obesity (BMI > 30) compared to matched non-ADHD controls, regardless of whether or not they were medicated.
Those diagnosed with ADHD, but not on methylphenidate, had 40% greater odds of being overweight or obese, and over 55% greater odds of becoming severely obese, relative to matched non-ADHD controls.
Methylphenidate users had 60% greater odds of being overweight or obese, and over 85% greater odds of becoming severely obese, relative to matched non-ADHD controls.
There were signs of a dose-response effect. Less than a year’s exposure to methylphenidate was associated with roughly 75% greater odds of becoming severely obese, whereas exposure over a year or more raised the odds 2.3-fold, relative to matched non-ADHD controls. Using MPH increased the prevalence of overweight from 43.2% to 46.5%, with a greater prevalence among those using MPH for more than one year (50.5%).
It is important to note that most of this effect was from ADHD itself, with methylphenidate only assuming a predominant role in severe obesity among those with longer-term exposure to the medicine.
As for height, children with ADHD were no more likely to be short of stature than matched non-ADHD controls. Being prescribed methylphenidate was associated with slightly greater odds (7%) of being short of stature, but there was no dose-response relationship.
Conclusion:
The team concluded, “patients with ADHD, particularly those treated with MPH, had a higher BMI and shorter height at adulthood than individuals without ADHD. Although the observed height difference was clinically small in both sexes and age groups, the findings suggest that long-term MPH exposure may be associated with growth and body composition, highlighting the need for regular monitoring of growth.” They also point out that “Despite these findings, the clinical relevance should be interpreted with caution. In our cohort, the mean difference in height was less than 1 cm (eg, maximum −0.6 cm in females) below commonly accepted thresholds for clinical significance.” Likewise, increases in overweight/BMI were small.
One problem with interpreting the BMI/obesity results is that some of the genetic variants that cause ADHD also cause obesity. If that genetic load increases with severity of ADHD than the results from this study are confounded because those with more severe ADHD are more likely to be treated than those with less severe ADHD.
Due to these small effects along with the many study limitations noted by the authors, these results should be considered alongside the well-established benefits of methylphenidate treatment.
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