December 31, 2021

Is there a short-term relationship between air pollution and severity of ADHD symptoms?

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.

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NEW STUDY: Understanding the Gap Between ADHD Clinical Trials and Real-World Patients

Background 

ADHD (Attention-Deficit/Hyperactivity Disorder) is one of the most studied neurodevelopmental conditions, with many clinical trials evaluating the effectiveness and safety of various medications. These trials, known as randomized controlled trials (RCTs), are considered the gold standard for assessing treatments. However, strict eligibility criteria often exclude many real-world patients, raising questions about whether the findings from these trials apply to everyday clinical settings.

Our latest study sheds light on this issue, revealing just how many individuals with ADHD might be excluded from RCTs and the impact this exclusion has on their treatment outcomes. 

Method

Researchers used Swedish national registries to analyze data from 189,699 individuals diagnosed with ADHD who started medication between 2007 and 2019. They applied exclusion criteria from 164 international RCTs to identify who would have been considered ineligible for these trials in order to determine the proportion of individuals with ADHD who would not meet the eligibility criteria for RCTs.  

Key Findings

Many Patients Are Ineligible for Clinical Trials:

  • Over half (53%) of the study population would have been ineligible for ADHD medication trials.
  • Adults were most likely to be excluded (74%), followed by adolescents (35%) and children (21%).

Ineligible Patients Face Unique Challenges:

  • Treatment Switching: Ineligible individuals were more likely to switch medications within the first year (14% higher likelihood compared to eligible patients).
  • Medication Discontinuation: They were slightly less likely to stop taking their medication during the first year.

Higher Risk of Adverse Outcomes:

  • Ineligible patients experienced significantly higher rates of psychiatric hospitalizations and health issues such as depression, anxiety, and substance use disorders. For instance:some text
    • Psychiatric hospitalizations: Nearly 10 times more likely.
    • Specialist visits for substance use disorders: About 15 times more likely.
    • Anxiety-related visits: Over 11 times more likely.

What This Means

These findings highlight a major gap between the controlled environments of clinical trials and the realities faced by individuals with ADHD in everyday life. While RCTs provide valuable insights, their restrictive criteria often exclude patients with more complex health profiles or co-existing conditions. This limits the generalisability of trial results, meaning that treatment guidelines based solely on RCTs may not fully address the needs of all patients.

Conclusion

This study demonstrated that a significant proportion of individuals with ADHD, particularly adults, do not meet the eligibility criteria for standard RCTs. These results emphasize the importance of bridging the gap between research settings and real-world applications. By recognizing and addressing the limitations of RCTs, we can work towards more equitable and effective ADHD treatment strategies for everyone.

January 14, 2025

Where Does ADHD Fit in the Psychopathology Hierarchy? A Symptom-Focused Study

NEWS TUESDAY: Where Does ADHD Fit in the Psychopathology Hierarchy? A Symptom-Focused Study

Background:

Our understanding of Attention-deficit/hyperactivity disorder (ADHD) has grown and evolved considerably since it first appeared in the DSM-II as “Hyperkinetic Reaction of Childhood.”  This study aimed to find the disorder’s placement within the modern psychopathology classification systems like the Hierarchical Taxonomy Of Psychopathology (HiTOP). 

The HiTOP model aims to address limitations of traditional classification systems for mental illness, such as the DSM-5 and ICD-10, by organizing psychopathology according to evidence from research on observable patterns of mental health problems.. Is ADHD best categorized under externalizing conditions, neurodevelopmental disorders, or something else entirely? A recent study by Zheyue Peng, Kasey Stanton, Beatriz Dominguez-Alvarez, and Ashley L. Watts takes a closer look at this question using a symptom-focused approach.

The Study:

Traditionally, ADHD has been associated with externalizing behaviors, such as impulsivity and hyperactivity, or with neurodevelopmental traits, like cognitive delays. However, this study challenges the idea of placing ADHD into a single category. Instead, it maps ADHD symptoms across three major psychopathology spectra: externalizing, neurodevelopmental, and internalizing.

The findings reveal that ADHD symptoms don’t fit neatly into one box. For example, symptoms like impulsivity, poor school performance, and low perseverance were strongly associated with externalizing behaviors. On the other hand, cognitive disengagement (e.g., daydreaming, blank staring) and immaturity were closely linked to neurodevelopmental challenges. Interestingly, cognitive disengagement also showed ties to internalizing symptoms, such as anxiety or depression.

This research underscores the complexity of ADHD. Rather than treating ADHD as a single, unitary construct, the study advocates for a symptom-based approach to better understand and treat individuals. By acknowledging that ADHD symptoms relate to multiple psychopathology spectra, clinicians and researchers can move toward more nuanced classification systems and targeted interventions.

Conclusion: 

Ultimately, this study highlights the need for modern systems to move beyond rigid categories and adopt a more flexible, symptom-focused framework for understanding ADHD’s place in psychopathology.

January 6, 2025

Meta-analyses Find Dose-response Association Between Lead Exposure and Subsequent ADHD

Meta-analyses Find Dose-response Association Between Lead Exposure and Subsequent ADHD

Background:

Exposure to heavy metals like lead, arsenic, mercury, cadmium, and manganese is known to harm developing nervous systems. However, past studies on whether heavy metals specifically increase the risk of ADHD have shown mixed results.

A research team from China (Gu et al., 2024) reviewed medical studies and conducted meta-analyses to better understand this issue.

Methods:

The team included studies on children and teens, focusing on cohort studies, case-control studies, and cross-sectional studies. They only used articles written in English and required validated biomonitoring (like blood tests) to measure heavy metal exposure. ADHD diagnoses had to come from clinical evaluations.

To be included, studies had to report effect sizes such as odds ratios and relative risks with confidence intervals. The team focused on comparisons between groups with high, low, or no exposure, which made it harder to analyze dose-response relationships.

They also evaluated the quality of each study. All cohort studies were rated high-quality. Of the 15 case-control studies, 6 were high-quality, and 9 were moderate-quality. Among cross-sectional studies, only 2 were high-quality, and the rest were moderate-quality.

Key Findings:
  1. Lead Exposure and ADHD:some text
    • A meta-analysis of 22 studies with over 20,000 participants found that early exposure to lead was linked to about twice the odds of an ADHD diagnosis compared to unexposed children.
    • However, results varied widely among studies, and signs of publication bias were detected. After adjusting for this bias, the increased odds dropped to about 50%.
    • A dose-response relationship was found:some text
      • Blood lead levels of 2.5 µg/dL increased ADHD risk by 1.8 times.
      • Levels of 5 µg/dL increased the risk 2.5 times.
      • Levels of 7.5 µg/dL increased the risk 2.75 times.
      • Levels of 10 µg/dL tripled the risk.
  2. Other Metals:some text
    • No significant links were found between ADHD and exposure to arsenic, mercury, cadmium, or manganese. Fewer studies were available for these metals, and participant numbers were much smaller:some text
      • Arsenic exposure: 25% higher odds of ADHD (4 studies, 3,116 participants).
      • Mercury exposure: 25% higher odds (6 studies, 2,916 participants).
      • Cadmium exposure: 25% higher odds (5 studies, 2,419 participants).
      • Manganese exposure: 45% higher odds (6 studies, 1,664 participants).
  3. Austrian Study: An Austrian team (Rosenauer et al., 2024) also conducted a meta-analysis on lead exposure and ADHD. They included 14 studies with over 7,600 participants and found:some text
    • Lead exposure increased the odds of ADHD by about 25%.
    • Studies focusing on higher lead levels found a 43% increased risk, supporting a dose-response relationship.
    • Study results were consistent, with no signs of publication bias.
Conclusion:

There was no evidence linking ADHD to other heavy metals like arsenic, mercury, cadmium, or manganese.  Both meta-analyses suggest that lead exposure is associated with the risk for ADHD.  However, because these studies cannot rule out other explanations, one cannot conclude that lead exposure causes ADHD.  For example, other work shows that people with ADHD are likely to have lower incomes than those without ADHD.  

January 17, 2025