August 1, 2024

Meta-analysis finds association of lead and organophosphate exposure with subsequent childhood ADHD, little to none for mercury, and none for anesthesia, cadmium, hexachlorobenzene, and PCB

Lead’s neurotoxicity is well established, and organophosphate pesticides were deliberately developed first as nerve agents in warfare and then as insecticides.  

Noting that “Epidemiologic research on chemical exposures associated with the development of ADHD is numerous; however, studies have employed various methods, and, in some cases, have resulted in seemingly conflicting results,” a U.S. study team has performed an updated meta-analysis applying “identical meta-analytic techniques to the literature on the associations between earlier chemical exposures and later ADHD.”

Lead

Meta-analysis of eleven studies reporting dichotomous outcomes with a combined 7,566 participants found children exposed to lead were almost twice as likely to subsequently be diagnosed with ADHD as their unexposed peers.  

A second meta-analysis, of thirteen studies reporting continuous outcomes with a total of 1,775 participants, found a small effect size increase in ADHD diagnosis from exposure to lead.

Interestingly, meta-analysis of four studies with a combined 4,360 participants found no association between prenatal lead exposure and subsequent ADHD diagnosis.

On the other hand, meta-analysis of seven studies combining almost five thousand participants reported that cumulative lead exposure more than doubled the likelihood of subsequent ADHD.

In other words, it’s not so much prenatal exposure as exposure after birth that is associated with increased risk.

Organophosphates

Meta-analysis of four studies reporting continuous outcomes with a combined total of 692 persons likewise found a small effect size increase in ADHD diagnosis from exposure to organophosphates.

Mercury

Meta-analysis of six studies reporting continuous outcomes with a combined total of over 17 thousand participants found a tiny effect size increase in ADHD diagnosis from exposure to mercury.

On the other hand, meta-analysis of ten studies reporting dichotomous outcomes with a combined total of over 650,000 persons found no association whatsoever between mercury exposure and subsequent diagnosis of ADHD.

Other exposures

Meta-analysis of five studies involving more than 34,000 participants found no evidence of an association between exposure to anesthesia and ADHD.

Meta-analysis of three studies encompassing 1,739 individuals found no evidence of an association between exposure to cadmium and ADHD.

Meta-analysis of four studies combining more than 2,400 persons found no evidence of an association between exposure to hexachlorobenzene and ADHD.

A pair of meta-analyses, one of three studies reporting dichotomous outcomes including 2,050 participants, the other of nine studies reporting continuous outcomes involving almost three thousand participants, both found no evidence of an association between exposure to polychlorinated biphenyls (PCBs) and ADHD.

There was little variability (heterogeneity) among results reported by individual studies within these meta-analyses, but a serious limitation was the failure to check for publication bias.

The authors concluded, “given our findings related to exposure to mercury, organophosphates, and PCBs, further research may be helpful to better characterize these relationships. Many of our effect sizes were small, which is consistent with the literature indicating that many genetic and environmental factors contribute to ADHD. … Furthermore, our findings support existing regulations of certain chemicals,” and “may inform future regulatory decisions”

Lina V. Dimitrov, Jennifer W. Kaminski, Joseph R. Holbrook, Rebecca H. Bitsko, Michael Yeh, Joseph G. Courtney, Brenna O’Masta, Brion Maher, Audrey Cerles, Katherine McGowan, and Margaret Rush, “A Systematic Review and Meta-analysis of Chemical Exposures and Attention-Deficit/Hyperactivity Disorder in Children,” Prevention Science (2024), 25 (Suppl 2):S225–S248, https://doi.org/10.1007/s11121-023-01601-6.

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Meta-analysis Reports Executive Function Gains from Exercise Interventions for ADHD

Background:

The development of ADHD is strongly associated with functional impairments in the prefrontal cortex, particularly the dorsolateral prefrontal cortex, which plays a key role in maintaining attention and controlling impulses. Moreover, imbalances in neurotransmitters like dopamine and norepinephrine are widely regarded as major neurobiological factors contributing to ADHD. 

Executive functions are a group of higher-order cognitive skills that guide thoughts and actions toward goals. “Executive function” refers to three main components: inhibitory control, working memory, and cognitive flexibility. Inhibitory control helps curb impulsive actions to stay on track. Working memory allows temporary storage and manipulation of information for complex tasks. Cognitive flexibility enables switching attention and strategies in varied or demanding situations. 

Research shows that about 89% of children with ADHD have specific executive function impairments. These difficulties in attention, self-control, and working memory often result in academic and social issues. Without timely intervention, these issues can lead to emotional disorders like depression, anxiety, and irritability, further affecting both physical health and social development. 

Currently, primary treatments for executive function deficits in school-aged children with ADHD include medication and behavioral or psychological therapies, such as Cognitive Behavioral Therapy (CBT). While stimulant medications do improve executive function, not all patients are able to tolerate these medications. Behavioral interventions like neurofeedback provide customized care but show variable effectiveness and require specialized resources, making them hard to sustain. Safer, more practical, and long-lasting treatment options are urgently needed. 

Exercise interventions are increasingly recognized as a safe, effective way to improve executive function in children with ADHD. However, systematic studies on school-aged children remain limited.  

Moreover, there are two main scoring methods for assessing executive function: positive scoring (higher values mean better performance, such as accuracy) and reverse scoring (lower values mean better performance, such as reaction time). These different methods can affect how results are interpreted and compared across studies. This meta-analysis explored how different measurement and scoring methods might influence results, addressing important gaps in the research. 

The Study:

Only randomized controlled trials (RCTs) involving school-aged children (6–13 years old) diagnosed with ADHD by DSM-IV, DSM-5, ICD-10, ICD-11, or the SNAP-IV scale were included. Studies were excluded if the experimental group received non-exercise interventions or exercise combined with other interventions. 

Cognitive Flexibility 

Using positive scoring, exercise interventions were associated with a narrowly non-significant small effect size improvement relative to controls (eight RCTs, 268 children). Using reverse scoring, however, they were associated with a medium effect size improvement (eleven RCTs, 452 children). Variation (heterogeneity) in individual RCT outcomes was moderate, with no sign of publication bias in both instances. 

Inhibitory Control 

Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (ten RCTs, 421 children). Using reverse scoring, there was an association with a medium effect size improvement (eight RCTs, 265 children). Heterogeneity was moderate with no sign of publication bias in either case. 

Working Memory 

Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (six RCTs, 321 children). Using reverse scoring, the exercise was associated with a medium effect size improvement (five RCTs, 143 children). Heterogeneity was low with no indication of publication bias in both instances. 

Conclusion:

The team concluded, “Exercise interventions can effectively improve inhibitory control and working memory in school-aged children with ADHD, regardless of whether positive or reverse scoring methods are applied. However, the effects of exercise on cognitive flexibility appear to be limited, with significant improvements observed only under reverse scoring. Moreover, the effects of exercise interventions on inhibitory control, working memory, and cognitive flexibility vary across different measurement paradigms and scoring methods, indicating the importance of considering these methodological differences when interpreting results.” 

Although this work is intriguing, it does not show that exercise significantly improves the symptoms of ADHD in children. This means that exercise, although beneficial for many reasons, should not be viewed as a replacement for evidence-based treatments for the disorder.

December 3, 2025

Here’s What the Wall Street Journal Got Wrong about the Medication Treatment of ADHD Patients: A Lesson in Science Media Literacy

A recent Wall Street Journal article raised alarms by concluding that many children who start medication for ADHD will later end up on several psychiatric drugs. It’s an emotional topic that will make many parents, teachers, and even doctors worry: “Are we putting kids on a conveyor belt of medications?”

The article seeks to shine a light on the use of more than one psychiatric medication for children with ADHD.   My biggest worry about the article is that it presents itself as a scientific study because they analyzed a database.  It is not a scientific study.  It is a journalistic investigation that does not meet the standards of a scientific report..

The WJS brings attention to several issues that parents and prescribers should think about. It documents that some kids with ADHD are on more than one psychiatric medication, and some are receiving drugs like antipsychotics, which have serious side effects.  Is that appropriate? Access to good therapy, careful evaluation, and follow-up care can be lacking, especially for low-income families.  Can that be improved?  On that level, the article is doing something valuable: it’s shining a spotlight on potential problems.

It is, of course, fine for a journalist to raise questions, but it is not OK for them to pretend that they’ve done a scientific investigation that proves anything. Journalism pretending to be science is both bad science and bad journalism.

Journalism vs. Science: Why Peer Review Matters

Journalists can get big datasets, hire data journalists, and present numbers that look scientific.  But consider the differences between Journalism and Science. These types of articles are usually checked by editors and fact-checkers. Their main goals are:

 Is this fact basically correct?

 Are we being fair?

 Are we avoiding legal problems?

But editors are not qualified to evaluate scientific data analysis methods.  Scientific reports are evaluated by experts who are not part of the project.  They ask tough questions like: 

Exactly how did you define ADHD? 

How did you handle missing data? 

Did you address confounding? 

Did you confuse correlation with causation?

If the authors of the study cannot address these and other technical issues, the paper is rejected.

The WSJ article has the veneer of science but lacks its methodology.  

Correlation vs. Causation: A Classic Trap

The article’s storyline goes something like this:  A kid starts ADHD medication.  She has additional problems or side effects caused by the ADHD medications.   Because of that, the prescriber adds more drugs.  That leads to the patient being put on several drugs.  Although it is true that some ADHD youth are on multiple drugs, the WSJ is wrong to conclude that the medications for ADHD cause this to occur.  That simply confuses correlation with causation, which only the most naïve scientist would do.

In science, this problem is called confounding. It means other factors (like how severe or complex a child’s condition is) explain the results, not just the thing we’re focused on (medication for ADHD). 

The WSJ analyzed a database of prescriptions.  They did not survey the prescribers who made the prescriptions of the patients who received them.  So they cannot conclude that ADHD medication caused the later prescriptions, or that the later medications were unnecessary or inappropriate. 

Other explanations are very likely.   It has been well documented that youth with ADHD are at high risk for developing other disorders such as anxiety, depression,  and substance use.  The kids in the WSJ database might have developed these disorders and needed several medications.  A peer-reviewed article in a scientific journal would be expected to adjust for other diagnoses. If that is not possible, as it is in the case of the WSJ’s database, a journal would not allow the author to make strong conclusions about cause-and-effect.

Powerful Stories Don’t Always Mean Typical Stories

The article includes emotional accounts of children who seemed harmed by being put on multiple psychiatric drugs.  Strong, emotional stories can make rare events feel common.  They also frighten parents and patients, which might lead some to decline appropriate care. 

These stories matter. They remind us that each data point is a real person.  But these stories are the weakest form of data.  They can raise important questions and lead scientists to design definitive studies, but we cannot use them to draw conclusions about the experiences of other patients.  These stories serve as a warning about the importance of finding a qualified provider,  not as against the use of multiple medications.  That decision should be made by the parent or adult patient based on an informed discussion with the prescriber.

Many children and adults with ADHD benefit from multiple medications. The WSJ does not tell those stories, which creates an unbalanced and misleading presentation.  

Newspapers frequently publish stories that send the message:  “Beware!  Doctors are practicing medicine in a way that will harm you and your family.”   They then use case studies to prove their point.  The title of the article is, itself, emotional clickbait designed to get more readers and advertising revenue.  Don’t be confused by such journalistic trickery.

What Should We Conclude?

Here’s a balanced way to read the article.  It is true that some patients are prescribed more than one medication for mental health problems.  But the article does not tell us whether this prescribing practice is or is not warranted for most patients.  I agree that the use of antipsychotic medications needs careful justification and close monitoring.  I also agree that patients on multiple medications should be monitored closely to see if some of the medications can be eliminated.  Many prescribers do exactly that, but the WSJ did not tell their stories.  

It is not appropriate to conclude that ADHD medications typically cause combined pharmacotherapy or to suggest that combined pharmacotherapy is usually bad. The data presented by the WSJ does not adequately address these concerns.  It does not prove that medications for ADHD cause dangerous medication cascades.

We have to remember that even when a journalist analyzes data, that is not the same as a peer-reviewed scientific study. Journalism pretending to be science is both bad science and bad journalism.

Oppositional Defiant Disorder, Autism, and ADHD: New Research Examines the Connection

Oppositional Defiant Disorder (ODD)—a pattern of chronic irritability, anger, arguing, or defiance—is one of the most challenging behavioral conditions families and clinicians face. 

A new study involving 2,400 children ages 3–17 offers one of the clearest pictures yet. Using parent-reported data from the Pediatric Behavior Scale, researchers compared how often ODD appears in Autism spectrum disorder (ASD), ADHD-Combined presentation (ADHD-C), ADHD-Inattentive presentation (ADHD-I), and those with both ASD and ADHD.

Results

ADHD-Combined + ODD: The Highest-Risk Group

Children with ADHD-Combined presentation show both hyperactivity/impulsivity and inattention.  They had the highest ODD rates of any single diagnosis: 53% of kids with ADHD-Combined met criteria for ODD.

But when autism was added to ADHD-Combined, the prevalence jumped to 62%. This group also had the highest overall ODD scores, suggesting more severe or more impairing symptoms. 

This synergy matters: while autism alone increases ODD risk, the presence of ADHD-Combined is what pushes prevalence into the majority range. Other groups showed lower, but still significant, rates of ODD:

  • Autism + ADHD-Inattentive: 28%
  • Autism Only: 24%
  • ADHD-Inattentive Only: 14%

These findings echo what clinicians often see: children with inattentive ADHD, while struggling significantly with attention and learning, tend to show fewer behavioral conflict patterns than those with hyperactive/impulsive symptoms.

It is important to note that ODD is considered to have two main components. Across all diagnostic groups, ODD consistently broke down into these two components: either Irritable/Angry (emotion-based) or Oppositional/Defiant (behavior-based). But the balance between these components differed depending on diagnosis. Notably, Autism + ADHD-Combined showed higher levels of the irritable/angry component than ADHD-Combined alone. The oppositional/defiant component did not differ much between groups. This suggests that autism elevates the emotional side of ODD more than the behavioral side, which is important for clinicians to note before tailoring interventions.

Understanding ADHD , ASD, & Comorbidity:

The study notes that autism, ADHD, and ODD often cluster together, with 55–90% comorbidity in some combinations.

As the authors explain, The high co-occurrence of ADHD-Combined in autism (80% in our study) largely explains the high prevalence of ODD in autism.” 

Clinical Implications: Why This Study Matters

The researchers point to a straightforward recommendation: clinicians shouldn’t evaluate these conditions in isolation. A child referred for autism concerns might also be struggling with ADHD. A child referred for ADHD might have undiagnosed ODD. And ignoring one disorder can undermine treatment for the others.

Evidence-based interventions (behavioral therapy, parent training, school supports, and/or medication) can reduce symptoms across all three diagnoses while improving long-term outcomes, including overall quality of life.

November 21, 2025