November 19, 2021

How social disadvantages affect risk of ADHD

Danish health care is universal and free. That means there is very complete data available that covers the entire population. The health registers are linked to other national registers that provide access to socioeconomic information. That offers unusual opportunities to research correlations across an entire national population.

Moreover, the health care system requires a high standard for diagnosis of ADHD - evaluation by specialist doctors or psychiatrists rather than a general practitioner. An exception is when parents seek a diagnosis from a private practicing child psychiatrist, in which case diagnostic registration is not mandatory and data is therefore incomplete.

A trio of Danish researchers used the country' national registers to conduct a nationwide population cohort study to explore the cumulative effects of social disadvantages as risk factors for being diagnosed with ADHD.

They looked at all 632,725 children born in Denmark during the 1990s, of which 23,287 (3.7 percent) either had a registered diagnosis in the Patient Registry or else were undergoing ADHD treatment before age 18. Of these, 12,610 children had a registered ADHD diagnosis and entered medical treatment, 4,049 children had a registered diagnosis with no medical treatment, and 6,628 children entered medical treatment with no registered diagnosis. The latter were presumably diagnosed by private practicing psychiatrists. Adjustments were made for gender, immigrant status, birth characteristics (weight, gestational age), single-parenthood, parent ADHD diagnosis, and the number of children in the household.

The study determined that parental educational attainment had the largest effect on the risk of ADHD. Having parents who completed no more than the minimum compulsory education was associated with a 3.5 percentage point higher risk of getting an ADHD diagnosis. Completing no more than upper secondary education was associated with a 1.3 percent higher risk. But there was a sharp bifurcation in the two alternative components of upper secondary education. Children of parents who completed a vocational track faced a 1.7 percent increase in risk, whereas those whose parents completed a college preparatory track faced a negligible 0.17 percent increase.

Parental unemployment also had a significant effect. Youths whose parents were unemployed most of the year faced a 2.1 percent higher risk of ADHD, whereas those whose parents were unemployed less than half the year faced a 1.3 percent higher risk.

Relative income poverty had a comparable impact. Children of parents in the lowest income quintile faced a 2.3 percent higher risk of ADHD than those of parents in the uppermost income quintile. Those in the second-lowest quintile faced a 1.9 percent higher risk than those in the uppermost quintile; those in the middle quintile a 1.3 percent higher risk, and those in the second-highest quintile a 0.8 percent higher risk.

All three cases showed a dose-response relationship, in which higher gradations of social disadvantage were associated with higher levels of risk.

Since these social disadvantages often overlap, the researchers looked at combinations as well and found them to be roughly additive in effect. Parental unemployment plus relative income poverty was associated with a 1.9 percent higher risk of offspring ADHD. Parental unemployment plus completion of no more than compulsory education was associated with a 3.2 percent higher risk. Parental relative income poverty plus completion of no more than compulsory education produced a 4.2 percent higher risk. Finally, Parental relative income poverty plus completion of no more than compulsory education plus unemployment was associated with a 4.9 percent higher risk.

The authors concluded, "This study shows that specific and well-measured parental social disadvantages in terms of unemployment, relative income poverty, and low educational attainment independently affect the risk of ADHD."

Maria Kellow, Chunsen Wu, Carsten Obel, "Cumulative social disadvantage and risk of attention deficit hyperactivity disorder: Results from a nationwide cohort study," SSM - Population Health (2020) 10, 100548, https://doi.org/10.1016/j.ssmph.2020.100548.

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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