Effect of Physical Activity on Attention in School-age Children with ADHD: Systematic Review and Meta-Analysis

Overview

Attention is a critical determinant of academic achievement, influencing domains such as language, literacy, and mathematics. To explore whether physical activity can improve attention in children with ADHD, an international team conducted a meta-analysis of peer-reviewed studies. The goal was to evaluate the impact of various physical activity regimens on attention-related outcomes in this population.

Methods

The researchers performed a comprehensive search of the medical literature to identify studies examining the effects of physical activity on attention in schoolchildren with ADHD. They included 10 studies with a total of 474 participants in their meta-analysis. The studies evaluated two main types of physical activity:

  • Mentally engaging physical activities
  • Aerobic exercise

Additionally, they examined variations based on the frequency, duration, and type of control groups used in the studies. To assess consistency, they also analyzed heterogeneity (variability of outcomes) and checked for potential publication bias.

Summary

Key findings from the meta-analysis include:

  1. Effectiveness of Mentally Engaging Activities:some text
    • Seven studies (168 participants) involving mentally engaging physical activities showed large reductions in attention problems.
    • Heterogeneity was significantly reduced for these studies.
  2. Effectiveness of Aerobic Exercise:some text
    • Three studies (306 participants) using aerobic exercise alone found no improvements in attention.
  3. Impact of Control Groups:some text
    • Studies with no intervention as a control group (4 studies, 81 participants) reported large improvements in attention problems.
    • Those comparing physical activity with other interventions (6 studies, 393 participants) found only small improvements.
  4. Frequency and Duration:some text
    • Duration of physical activity made little difference. Studies with sessions of an hour or more had slightly better outcomes, but the difference was not significant.
    • Surprisingly, lower frequency was more effective:some text
      • One to two sessions per week (7 studies, 162 participants) led to large reductions in attention problems.
      • Three or more sessions per week (3 studies, 312 participants) showed no improvement.
Conclusion

The authors concluded that mentally engaging exercise is more effective than aerobic exercise in improving attention problems in schoolchildren with ADHD. Furthermore, higher frequency and longer duration of physical activity do not necessarily yield better outcomes.

This research underscores the importance of tailoring physical activity interventions to emphasize cognitive engagement over intensity or duration. By refining strategies, educators and parents can better support children with ADHD in achieving academic success.   But take note:  given the results from controlled studies, it seems clear that if there is a positive effect of exercise, it is very small so should not replace standard treatments for ADHD.  

NEWS TUESDAY: How Stimulant Use in Childhood ADHD May Impact Brain Connectivity and Symptom Improvement

Previous studies have examined how stimulant medications affect the brain in controlled settings, but less is known about their impact in real-world conditions, where children may not always take their medication consistently or may combine it with other treatments. A new study leverages data from the Adolescent Brain Cognitive Development (ABCD) study to explore how real-world stimulant use impacts brain connectivity and ADHD symptoms over two years.

Changes in Brain Connectivity Researchers used brain imaging data from the ABCD study to examine the functional connectivity—communication between brain areas—of six regions within the striatum, a brain area involved in motivation and movement control. They focused on how stimulant use influenced connectivity between the striatum and other networks involved in executive functioning and visual-motor control.

The study found that stimulant exposure was linked to reduced connectivity between key striatal areas (such as the caudate and putamen) and large brain networks, including the frontoparietal and visual networks. These changes were more pronounced in children taking stimulants compared to those who were not medicated, as well as compared to typically developing children. Importantly, this reduction in connectivity seemed to regulate certain brain networks that are typically altered in children with ADHD.

Symptom Improvement In addition to brain changes, 14% of children taking stimulants experienced a significant reduction in ADHD symptoms over the two-year period. These children showed the strongest connectivity reductions between the right putamen and the visual network, suggesting that stimulant-induced connectivity changes may contribute to improvements in visual attentional control, which is a common challenge for children with ADHD.

Why This Matters This study is one of the first to examine how stimulant use in real-world conditions affects brain networks in children with ADHD over time. The findings suggest that stimulants may help normalize certain connectivity patterns associated with ADHD, particularly in networks related to attention and control. These insights could help clinicians better understand the potential long-term effects of stimulant treatment and guide personalized approaches to ADHD management.

Conclusion Stimulant medications appear to alter striatal-cortical connectivity in children with ADHD, with some changes linked to symptom improvement. This research highlights the potential for stimulant medications to impact brain networks in ways that support attention and control, highlighting the importance of understanding how real-world medication use influences ADHD treatment outcomes.

December 3, 2024

Exploring the Link Between ADHD and Student-Teacher Relationships: A Meta-Analysis

Children with ADHD face significant challenges in academic and social settings, often including difficult interactions with teachers. This meta-analysis investigates the quality of student-teacher relationships for children with ADHD, focusing on two key dimensions: closeness and conflict. By synthesizing data from 27 studies encompassing 17,236 participants, the study aims to provide a comprehensive understanding of these dynamics and inform interventions to support both students and teachers.

Methods

A systematic review was conducted using databases such as PsycInfo, ERIC, and ProQuest. Researchers identified 47 effect sizes from 27 studies, examining the association between ADHD symptoms and the quality of student-teacher relationships. Relationship quality was assessed through two primary dimensions:

  1. Closeness – Warmth, positivity, and openness between the student and teacher.
  2. Conflict – Hostility, negativity, and tension in interactions.

Eight moderator analyses were also performed to explore how factors like grade level, gender, ADHD presentation, and comorbid conditions influenced these relationships.

Summary

The findings reveal that children with ADHD symptoms typically experience relationships with teachers characterized by lower levels of closeness and higher levels of conflict. Notably, externalizing behaviors such as hyperactivity and impulsivity are more strongly associated with conflict than inattentive symptoms. Moderator analyses showed that factors like gender, ADHD presentation, and age influence the severity of these relationship dynamics. For instance, younger children and those with hyperactive-impulsive presentations tend to have higher conflict levels with teachers.

Additionally, the research emphasizes the reciprocal nature of these relationships: ADHD symptoms may exacerbate teacher frustration, while negative teacher-student interactions can intensify student behavioral challenges.

Conclusion

This meta-analysis highlights the critical role of student-teacher relationships in the development of children with ADHD. The findings underline the need for targeted interventions that foster positive teacher-student interactions and reduce conflict. Addressing these relationship dynamics could enhance academic performance, social integration, and emotional well-being for children with ADHD. Future research should explore the causal pathways between ADHD symptoms and relationship quality to better inform educational strategies and support systems.

November 25, 2024

Patterns of Child and Adolescent Psychiatric Admissions During COVID-19: Key Insights from Clinical Data

A recent study from Istanbul sheds light on how psychiatric admissions and diagnoses changed during the first few months of the pandemic compared to previous periods, offering critical insights for parents, clinicians, and policymakers. 

This study, conducted by a team of researchers led by Ozalp Ekinci, examined psychiatric admissions among children and adolescents during 2019 and 2020. 

By looking at diagnosis rates for various psychiatric conditions, the researchers aimed to pinpoint shifts in the mental health landscape as a direct response to the pandemic.

Findings: A Closer Look at Diagnosis Patterns

The analysis revealed several notable trends in psychiatric diagnoses among children and adolescents:

  1. Autism Spectrum Disorder (ASD): ASD diagnoses were notably higher in the early pandemic phase (6.4% in Group A) compared to the same period in the previous year (3.6%). This increase could reflect heightened stress or changes in routines that may have exacerbated underlying symptoms, leading to more frequent clinical presentations.
  2. Obsessive-Compulsive Disorder (OCD) and Tic Disorders: OCD and tic disorder diagnoses also saw a rise, increasing from 1.7% in 2019 to 2.9% during the pandemic’s onset. It’s possible that pandemic-driven anxieties and hygiene concerns, as well as disruptions to typical routines, may have worsened symptoms in those predisposed to OCD and similar disorders.
  3. Intellectual Disability (ID): Diagnoses for ID rose from 2.1% (Group C) to 3.7% (Group A). This increase highlights the challenges faced by children with developmental and intellectual disabilities, who may have experienced heightened difficulty adapting to the many changes imposed by the pandemic.
  4. Attention-Deficit Hyperactivity Disorder (ADHD): ADHD diagnoses were significantly higher in the pandemic phase (59.8% for Group A vs. 49.7% for Group B). With altered school structures, remote learning, and restricted socialization, ADHD symptoms could have been amplified, making it harder for children to concentrate and adhere to routines.
  5. Depression: Depression diagnoses also saw a rise (4.1% in Group A vs. 2.2% in Group C). Isolation, disruption of daily activities, and reduced social interactions likely contributed to increased depressive symptoms, particularly in adolescents who rely heavily on peer support.
  6. Conduct Disorder (CD): Interestingly, CD diagnoses were lower during the pandemic phase compared to pre-pandemic levels (3.6% in Group A vs. 6.4% in Group B). The reduction in face-to-face interactions and less exposure to traditional school settings may have lessened some of the typical triggers associated with conduct-related issues.
Implications

This study’s findings highlight some key takeaways that can guide mental health support efforts for children and adolescents:

  1. Increased Need for Early Support in Neurodevelopmental Disorders: The rise in ASD and ADHD diagnoses points to the need for specialized support in times of crisis, particularly for children who depend on routine and structure. Families and educators should work to create consistent environments that help manage symptoms.
  2. Addressing Pandemic-Induced Anxiety: With heightened cases of OCD and tic disorders, it’s clear that the pandemic’s emphasis on cleanliness and health may have intensified anxiety-driven behaviors. Future mental health responses should include strategies to manage health-related fears and equip children with coping skills.
  3. Supporting Emotional Resilience in Adolescents: Depression was notably higher among young people during the pandemic onset, suggesting a critical need for access to counseling and peer support, especially in times of isolation. Developing robust virtual mental health resources and promoting mental well-being in schools can help support children and adolescents both in and out of school.
  4. Recognizing the Complexity of Behavioral Changes: The drop in conduct disorder diagnoses during the pandemic suggests a link between behavioral disorders and social settings. Understanding these dynamics could lead to more tailored interventions that account for environmental factors impacting behavior.
Conclusion: 

As we continue to see the effects of the COVID-19 pandemic on mental health, studies like this one serve as important reminders of the unique mental health needs of young people. Supporting children and adolescents through proactive and targeted mental health services—especially during times of crisis—will be crucial to fostering resilience and well-being in future generations.

November 19, 2024

Updated Analysis of ADHD Prevalence in the United States: 2018-2021

Attention-Deficit/Hyperactivity Disorder (ADHD) remains a prevalent condition among children and adolescents in the United States. A recent analysis based on the National Health Interview Survey (NHIS), conducted by the National Center for Health Statistics at the CDC, provides an updated look at ADHD prevalence from 2018 to 2021. Here’s a closer look at what the data reveals.

How the Survey Works

The NHIS is an annual survey primarily conducted through face-to-face interviews in respondents’ homes. Telephone interviews are used as a substitute in cases where travel is impractical. For each family interviewed, one child aged 3-17 is randomly selected for the survey through a computer program. Over the four years studied (2018-2021), a total of 26,422 households with children or adolescents participated.

Overall ADHD Prevalence and Age-Related Trends

The analysis found that 9.5% of children and adolescents in the United States had been diagnosed with ADHD, based on reports from family members. However, the prevalence varied significantly with age:

  • Ages 3-5: 1.5%
  • Ages 6-11: 9.6%
  • Ages 12-17: 13.4%

The increase in ADHD diagnosis with age underscores the importance of monitoring children’s developmental needs as they progress through school and adolescence.

Gender Differences: Higher Rates Among Males

The survey revealed a notable difference in ADHD prevalence between genders, with 12.4% of males diagnosed compared to 6.6% of females—nearly a two-to-one gap. This aligns with previous research indicating that ADHD is more frequently diagnosed in boys than girls, though awareness of how ADHD presents differently across genders is growing.

Family Income and ADHD Rates

Family income played a significant role in ADHD prevalence, particularly among lower-income groups:

  • Below the poverty line: 12.7%
  • Above the poverty line but less than twice that level: 10.3%
  • Above twice the poverty level: 8.5%

This pattern suggests that socioeconomic factors might influence the diagnosis and management of ADHD, with lower-income families possibly experiencing greater barriers to early diagnosis or consistent treatment.

Regional Differences Across the U.S.

Geographic location also impacted ADHD rates. Prevalence was highest in the South (11.3%), followed by the Midwest (10%), the Northeast (9.1%), and significantly lower in the West (6.9%). These variations could reflect regional differences in healthcare access, diagnostic practices, or cultural attitudes towards ADHD.

Stability Over Time

Despite these variations in demographics, the overall prevalence of ADHD remained relatively stable across the study period from 2018 to 2021, showing no significant changes by year.

What This Means for Families and Healthcare Providers

The findings from this updated analysis provide a clearer picture of ADHD’s prevalence across different demographic groups in the United States. They highlight the need for tailored approaches to diagnosis and care, taking into account factors like age, gender, income, and geographic location. With ADHD being a common condition affecting nearly 1 in 10 children, ongoing research and support for families are crucial to ensure that those with ADHD receive the care and resources they need.

Conclusion: 

This study reinforces the importance of awareness and early intervention, especially for families in underserved regions or those facing economic challenges. As clinicians and educators continue to support children with ADHD, understanding these demographic trends can help in creating more equitable access to diagnosis and treatment.

October 29, 2024

Meta-analysis Finds Strong Link Between Parental and Offspring ADHD

A large international research team has just released a detailed analysis of studies looking at the connection between parents' mental health conditions and their children's mental health, particularly focusing on ADHD (Attention Deficit Hyperactivity Disorder). This analysis, called a meta-analysis, involved carefully examining previous studies on the subject. By September 2022, they had found 211 studies, involving more than 23 million people, that could be combined for their analysis.

Most of the studies focused on mental disorders other than ADHD. However, when they specifically looked at ADHD, they found five studies with over 6.7 million participants. These studies showed that children of parents with ADHD were more than eight times as likely to have ADHD compared to children whose parents did not have ADHD. The likelihood of this result happening by chance was extremely low, meaning the connection between parental ADHD and child ADHD is strong.

Understanding the Numbers: How Likely Is It for a Child to Have ADHD?

The researchers wanted to figure out how common ADHD is among children of parents both with and without ADHD. To do this, they first analyzed 65 studies with about 2.9 million participants, focusing on children whose parents did not have ADHD. They found that around 3% of these children had ADHD.

Next, they analyzed five studies with over 44,000 cases where the parents did have ADHD. In this group, they found that 32% of the children also had ADHD, meaning about one in three. This is a significant difference—children of parents with ADHD are about ten times more likely to have the condition than children whose parents who do not have ADHD.

How Does This Compare to Other Mental Disorders in Parents?

The researchers also wanted to see if other mental health issues in parents, besides ADHD, were linked to ADHD in their children. They analyzed four studies involving 1.5 million participants and found that if a parent had any mental health disorder (like anxiety, depression, or substance use issues), the child’s chances of having ADHD increased by 80%. However, this is far less than the 840% increase seen in children whose parents specifically had ADHD. In other words, ADHD is much more likely to be passed down in families compared to other mental disorders.

Strengths and Weaknesses of the Research

The study had a lot of strengths, mainly due to the large number of participants involved, which helps make the findings more reliable. However, there were also some limitations:

  • The researchers did not look into "publication bias," which means they didn’t check whether only certain types of studies were included (those showing stronger results, for example), which could make the findings seem more extreme.
  • The team reported that differences between the studies were measured, but they didn’t explain clearly how these differences affected the results.
  • Most concerning, the researchers admitted that 96% of the studies they included had a "high risk of bias," meaning that many of the studies might not have been entirely reliable.

Conclusion

Despite these limitations, the research team concluded that their analysis provides strong evidence that children of parents with ADHD or other serious mental health disorders are at a higher risk of developing mental disorders themselves. While more research is needed to fill in the gaps, the findings suggest that it would be wise to carefully monitor the mental health of children whose parents have these conditions to provide support and early intervention if needed

Meta-analysis Finds Congenital Heart Disease Triples the Odds of ADHD in Children

Congenital heart disease (CHD) is a common birth defect where the heart’s blood vessels don’t develop normally before birth. This condition affects about 9% of all births worldwide, meaning about one in eleven babies is born with CHD. A recent analysis found that children with CHD have three times the risk of developing ADHD compared to children without CHD. However, that study only included five smaller studies, and almost 90% of the results varied between studies, making the findings less reliable. To improve on this, a team of researchers conducted a new, more thorough analysis.

Key Findings of the New Study

The updated analysis combined eleven studies, involving nearly 300,000 people. This larger study also confirmed that children with CHD are three times more likely to develop ADHD than those without CHD. Importantly, there was no evidence that the results were biased by only including studies that showed stronger results ("publication bias"). The variation between the studies (heterogeneity) was lower in this new analysis, down to a more manageable 60%.

Breaking Down the Study Types

The researchers looked at two types of studies: cohort studies and cross-sectional studies, and found different levels of risk:

  • Cohort studies: These studies followed groups of people over time. In this case, researchers compared children with CHD to those without it to see if ADHD developed later on. These five studies, with over 19,000 participants, found that children with CHD were 3.5 times more likely to develop ADHD.
  • Cross-sectional studies: These studies collected data at a single point in time, looking at children who already had CHD and checking if they had ADHD. The six cross-sectional studies, with more than 277,000 participants, found a lower, but still significant, 2.1 times higher risk of ADHD in children with CHD.

While both types of studies suggest a strong link between CHD and ADHD, cohort studies are more reliable because they track children over time, which helps researchers establish that CHD occurred before ADHD, suggesting a stronger cause-and-effect relationship. Both types of studies are observational.  In any observational study, researchers look at data without actively changing or controlling anything in the study environment. Because they aren't conducting controlled experiments, it's possible that some important factors, known as "confounding factors," aren't being measured or accounted for. These factors can influence both the exposure (what the study is investigating, like CHD) and the outcome (ADHD) in a way that creates an association that is apparent but not rea.

Adjustments for Other Factors

Nine of the studies, which included almost 300,000 participants, adjusted their findings to account for "confounding factors"—things like age, gender, or other health conditions that could also influence whether a child develops ADHD. Even after making these adjustments, the risk of ADHD in children with CHD was still three times higher.

Other Study Details

The researchers also found that the way ADHD was diagnosed—whether through clinical assessments or standardized symptom checklists—didn’t change the results much. Additionally, there was no major difference between studies done in the U.S. and those conducted in other countries, or between higher- and lower-quality studies.

Conclusion

The research team concluded that children born with congenital heart disease are at a much higher risk of developing ADHD than children without CHD. They suggested that children with CHD should be monitored more closely for ADHD as they grow up to ensure early intervention if needed.

September 30, 2024

Norwegian Population Study of Adolescents Finds Interpersonal Trauma Much More Likely Than Situational Trauma to Lead to ADHD Diagnosis

Potentially traumatic experiences (PTEs) refer to events where someone is exposed to situations that involve threats to life, serious injury, or danger to themselves or others. These events can include things like accidents, violence, or the death of someone close. PTEs are significant because they can have lasting effects on a person's mental health.

A research team from Norway, working with a collaborator from the U.S., used their country’s universal health care system to study how PTEs affect the mental health of children and adolescents in Hordaland County, which includes the city of Bergen. They wanted to see how experiencing PTEs influenced the likelihood of these young people seeking help from child and adolescent mental health services (CAMHS) or being diagnosed with psychiatric disorders, including ADHD.

In 2012, the study invited all 19,439 teenagers born between 1993 and 1995 in Hordaland County to participate. These teens were 16 to 19 years old at the time. Out of this group, 9,555 teens agreed to let the researchers link their personal data with the National Patient Registry (NPR), which keeps track of health records. There was no significant difference in the types or number of PTEs between those who agreed to this data sharing and those who did not.

After removing participants with incomplete information, the researchers were left with 8,755 teens. These teens’ psychiatric diagnoses, including ADHD, were taken from the NPR. The researchers asked the participants if they had ever experienced specific traumatic events, such as:

  • A serious accident or disaster
  • Violence from an adult
  • Witnessing violence against someone they cared about
  • Unwanted sexual actions
  • The death of someone close to them

If a participant reported experiencing the death of someone close, they were asked to specify who it was (a parent, sibling, grandparent, other family member, close friend, or romantic partner). One limitation of the study was that it did not ask about bullying, which could also be a traumatic experience.

Key Findings

The researchers divided the teens into three trauma groups based on their experiences:

  1. Low Trauma Group (88% of participants): These teens had not experienced anything more traumatic than the death of a grandparent.
  2. Interpersonal Trauma Group (6% of participants): These teens had experienced or witnessed violence, and some had also been exposed to sexual abuse, accidents, or the death of family members.
  3. Situational Trauma Group (6% of participants): These teens had experienced accidents and multiple deaths (including of close friends), but had less exposure to violence.

Other Important Factors

Teens in the situational and interpersonal trauma groups were more likely to see their economic situation as worse than those in the low trauma group. For example, 11% of the situational trauma group and 17% of the interpersonal trauma group considered themselves economically worse off, compared to just 6.1% of the low trauma group. Also, fewer parents of teens in the two higher trauma groups had higher levels of education, which can impact family support and resources.

ADHD and Trauma

After adjusting for gender and parental education, the researchers found that:

  • Teens in the situational trauma group were more than twice as likely to be diagnosed with ADHD compared to those in the low trauma group.
  • Teens in the interpersonal trauma group (who had experienced or witnessed more violence) were more than twice as likely to be diagnosed with ADHD compared to those in the situational trauma group.

The effect was even stronger when comparing the interpersonal trauma group to the low trauma group. Teens in the interpersonal trauma group were almost five times more likely to be diagnosed with ADHD than those in the low trauma group.

Study Limitations

One limitation of the study is that while the researchers acknowledged that sex and socioeconomic status (SES) are important factors in the relationship between trauma and psychiatric disorders, they did not directly adjust for SES. However, they did indirectly account for it by considering the education levels of the parents, which is closely related to SES.

Conclusion

The study showed that adolescents who experience more interpersonal trauma (like violence or sexual abuse) are at a significantly higher risk of being diagnosed with ADHD. The findings suggest that it’s important to pay special attention to teens who experience both situational and interpersonal traumas, especially those exposed to interpersonal violence. Early intervention and support could be key to helping these adolescents manage their mental health.

September 26, 2024

No Association Found Between Acetominophen Use During Pregnancy, Subsequent ADHD

Swedish Nationwide Population Study Finds No Association Between Acetaminophen Use During Pregnancy and Offspring ADHD

A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD). 

A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by: 

  • Confounding by indication, because acetaminophen is taken for infection, fever, and pain (including pain from autoimmune disease), which are themselves risk factors for neurodevelopmental disorders such as ADHD. 
  • Confounding by parental health and genetics, because neurodevelopmental disorders are highly heritable. 
  • Small sample sizes. 

Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings. 

The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding. 

Almost 186,000 of these children were exposed to acetaminophen during pregnancy.  

After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed. 

However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication.   High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage. 

Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.  

The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.” 

September 5, 2024

No Link Found Between In Utero Antipsychotic Exposure and ADHD

Meta-analysis with Millions of Participants Finds No Link Between Antipsychotic Use in Pregnancy and ADHD in Offspring

Antipsychotic medications are used to treat a variety of psychiatric disorders, including schizophrenia, bipolar disorder, sleeping problems, major depression, and severe anxiety. 

Untreated maternal mental illness is associated with poor health outcomes for both mothers and their offspring. On the other hand, one must guard against any potential direct harms of medications on development – including neurological development – of the fetus.  

Because prenatal use of antipsychotics is infrequent, previous observational studies have suffered from small sample sizes that have not enabled precise and reliable assessment of risk. The clinical decision about whether to continue antipsychotic treatment in patients who become pregnant has therefore remained inconclusive. 

In search of more reliable guidance, an international study team conducted a systematic search of the peer-reviewed medical literature to perform the first meta-analysis on this topic.  

They evaluated study quality and only included studies rated “good” or better. 

Identification of ADHD was determined by clinical diagnosis. 

Meta-analysis of four studies encompassing over eight million participants found a slight association. Children exposed to maternal antipsychotics during pregnancy were 11% more likely to be diagnosed with ADHD subsequently.  

But even in observational studies with millions of participants, such associations – especially when slight to begin with – could be due to unmeasured confounders. 

The team therefore compared children with gestational exposure to siblings from the same mother who were not exposed, to address shared genetic and social factors at the family level. 

Meta-analysis of two population-based sibling-matched studies with a combined total of over 4.6 million participants in Denmark, Norway, Sweden, Finland, Iceland, and Hong Kong found no significant association between gestational exposure to antipsychotic medications and subsequent diagnosis of ADHD

The team concluded, “Our systematic review and meta-analysis of observational studies indicates that the heightened risks of ADHD and ASD observed in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relation to the antipsychotic itself.” 

 

August 28, 2024

Study: No Link Between Childhood IBD Onset and Later ADHD

Danish Nationwide Population Study Finds No Association Between Onset of Inflammatory Bowel Disease in Children and Subsequent ADHD

Inflammatory bowel disease (IBD) consists of 2 main subtypes: Crohn’s disease and ulcerative colitis. Typical symptoms include abdominal pain, diarrhea, and rectal bleeding. Both are incurable, increase the risk of colorectal cancer, and often affect other organs as well. 

A single earlier study suggested a weak link between childhood-onset IBD and ADHD. 

A Danish research team used its country’s national registers – based on a single-payer national health insurance system that encompasses virtually the entire population – to include all 3,559 patients diagnosed with pediatric-onset IBD from 1998 through 2018.  

The team then matched these individuals five-to-one on age, age of diagnosis, year of diagnosis, sex, municipality of residence, and time period, with 17,795 individuals from the same pool who were free of IBD. 

ADHD was identified based on two criteria: clinical diagnoses in patient records, and methylphenidate stimulant prescriptions in the medications register. 

Overall, the team found no significant association between pediatric-onset IBD and ADHD. The same was true for both Crohn’s disease and ulcerative colitis. 

There were no differences in outcomes for boys or girls. 

There was also no significant association found using only ADHD diagnoses or only methylphenidate prescriptions.  

Among children and adolescents with IBD onset under age 14, there was a borderline significant association, but it was a negative one: They were less likely to subsequently be clinically diagnosed with ADHD or to receive prescriptions for methylphenidate.  

The team concluded, “Remarkably, we found a reduced risk of receiving methylphenidate and being diagnosed with ADHD, which merits further investigation.” 

ADHD and Exposure to Certain Chemicals and Heavy Metals

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”

August 1, 2024

Meta-analysis finds little to no association between prenatal cannabis exposure and offspring ADHD

Meta-analysis Finds Little-to-No Association Between Prenatal Cannabis Exposure and Offspring ADHD

Prevalence of cannabis use among pregnant women is on the rise with the spread of legalization. The most frequently reported reasons for use are to relieve stress or anxiety, nausea or vomiting, pain, and for recreation.

Given that the primary psychoactive ingredient of cannabis, ∆9-tetrahydrocannabinol (THC) is a small fat-soluble molecule that can easily cross the placenta, an Israeli-U.S. research team conducted a systematic search of the peer-reviewed medical literature for studies exploring possible neuropsychiatric effects on offspring.  

They included not only studies evaluating likelihood of ADHD, but also autism spectrum disorder, anxiety, depression, and psychotic symptoms. For each of these, adjustment was made for known confounding variables.

With that adjustment, meta-analysis of six studies with a total of over half a million (503,661) participants reported a 13% increase in the odds of ADHD in offspring of mothers using cannabis during pregnancy compared with offspring of mothers not using cannabis while pregnant.

That is generally considered a small effect size increase in risk. But there are multiple reasons to question even this minimal finding:

  • It barely achieved statistical significance.
  • A few studies used more reliable clinical diagnoses, while most just used ADHD symptom rating scales.
  • It is virtually impossible to eliminate all confounding variables. Twin studies come closest to fully accounting for otherwise unmeasured environmental and genetic confounders, but no such studies were included.
  • The team made no effort to evaluate publication bias.  
  • Almost all the participants (497,821) were in a single study, and that study – which relied on clinical diagnoses – did not find a significant association.

Meta-analysis of two studies with a total of 741 individuals reported a 20% increase in offspring use of cannabis among mothers who used cannabis during pregnancy, but once again this was subject to methodological shortcomings:

  • Two studies do not make for a robust meta-analysis, even more so with only 741 participants.
  • The result barely achieved statistical significance.
  • Publication bias was unaddressed.
  • Small effect sizes are questionable due to the virtual impossibility of eliminating all confounding variables, especially without twin studies.

Some studies have suggested a link between cannabis and psychotic symptoms. But meta-analysis of four studies combining over nineteen thousand persons found no significant association between maternal cannabis use during pregnancy and offspring psychotic symptoms.

Many studies have pointed to commonalities in the etiology of ADHD and autism spectrum disorder (ASD). Yet meta-analysis of five studies encompassing over half a million participants found absolutely no association between maternal prenatal cannabis use and ASD.  

The remaining meta-analyses also reported no association with depression or anxiety.

With the caution that absence of evidence is not the same as evidence of absence, it is by no means clear from what is presently known that prenatal cannabis exposure has any significant neuropsychiatric effects on offspring. And if further research finds any effects, they are likely to be minor.

July 26, 2024

Meta-Analysis: Young People with ADHD Experience Serious Social Cognition Impairments

Meta-analysis Concludes Children and Adolescents with ADHD Experience Serious Impairments in Social Cognition, Affecting Social Functioning

Children and adolescents with ADHD are known to have difficulties in relating to family members, peers, and teachers. Over the long run this can contribute to anxiety or even delinquency. 

Several cognitive functions that allow individuals to process social information and interact with others contribute to shaping everyday social interactions. These include: 

  • Theory of mind (ToM): Being able to attribute mental states to others, and thus explain and predict their behaviors. 
  • Empathy: Being able to feel an appropriate emotion in response to another person’s mental state, and thereby understand others’ feelings. 
  • Emotion recognition: Being able to identify emotions in facial expressions and other communication cues, such as voice and body position. 

A European research team performed a systematic search of the peer-reviewed medical literature to conduct meta-analyses of ToM, Empathy, Facial and Non-Facial Emotion Recognition in children and adolescents with ADHD when compared to typical development. As a comparison measure, they also included Everyday Social Skills (using self, parent, teacher, or clinician questionnaires/interviews of social skills) as an outcome. 

The search yielded 142 case-control studies (including dissertations) with a total of 16,283 participants. 

Meta-analysis of 82 studies with a combined total of 10,770 participants found a very large effect size impairment in everyday social skills among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates only strengthened the finding. There was no sign of publication bias. 

This was mirrored in three out of five measures of social cognition: 

  • Theory of mind (ToM): Meta-analysis of 49 studies with a total of 2,449 participants identified a large effect size impairment among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates made no difference in the outcome. There was no sign of publication bias. 
  • Empathy: Meta-analysis of twelve studies combining 916 individuals yielded a medium effect size impairment among children and adolescents with ADHD. But there were strong signs of publication bias, and the outcome lost significance after adjusting for covariates (perhaps because it became under-powered with three studies pooling only 151 persons). 
  • Facial emotion recognition: Meta-analysis of 43 studies with a total of 3,369 participants reported a medium effect size impairment among children and adolescents with ADHD after adjusting for covariates. There was absolutely no indication of publication bias. 
  • Non-facial emotion recognition: Meta-analysis of eight studies encompassing 707 persons reported a small effect size impairment with signs of publication bias that became insignificant after adjusting for covariates. 

The team concluded, “Our findings show that children and adolescents with ADHD have deficits in ToM, Facial Emotion Recognition, and Everyday Social Skills, three domains that warrant clinical attention.” 

July 22, 2024

Using Video Analysis and Machine Learning in ADHD Diagnosis

NEWS TUESDAY: Machine Learning and The Possible Future of Diagnosing ADHD

Objective and automatic assessment approach for diagnosing attention-deficit/hyperactivity disorder based on skeleton detection and classification analysis in outpatient videos

Typically, clinicians rely on both subjective and objective observations, patient interviews and questionnaires, as well as reports from family and (in the case of children) parents and teachers, in order to diagnose ADHD. 

A group of researchers are aiming to find a diagnostic test that is purely objective and utilizes recent technological advancements. The method they developed involves analyzing videos of children in outpatient settings, focusing on their movements. The study included 96 children, half of whom had ADHD and half who did not.

How It Works

  1. Video Recording: Children were recorded during their outpatient visits.
  2. Skeleton Detection: Using a tool called OpenPose, the researchers detected and tracked the children's skeletons (essentially a map of their body's movements) in the videos.
  3. Movement Analysis: The researchers analyzed these movements, looking at 11 different movement features. They specifically focused on the angles of different body parts and how much they moved.
  4. Machine Learning: Six different machine learning models were used to see which movement features could best distinguish between children with ADHD and those without.

Key Findings

  • Movement Differences: Children with ADHD showed significantly more movement in all the features analyzed compared to children without ADHD.
  • Thigh Angle: The angle of the thigh was the most telling feature. On average, children with ADHD had a thigh angle of about 157.89 degrees, while those without ADHD had an angle of 15.37 degrees.
  • High Accuracy: Using thigh angle alone, the model could diagnose ADHD with 91.03% accuracy. It was very sensitive (90.25%) and specific (91.86%), meaning it correctly identified most children with ADHD and correctly recognized most children without it.

This new method could potentially provide a more objective way to diagnose ADHD, reducing the reliance on subjective observations and reports. It can help doctors make more accurate diagnoses, ensuring that those who need help get it and that those who don't aren't misdiagnosed.

May 28, 2024

Nationwide population studies: atomoxetine not associated with birth defects

Nationwide population studies: atomoxetine not associated with birth defects

Treatment for ADHD among women of reproductive age is increasingly common. That means we need to know whether ADHD medications have any tendency to increase the risk of birth defects.

Treatment for ADHD among women of reproductive age is increasingly common. 

That means we need to know whether ADHD medications have any tendency to increase the risk of birth defects. Previous studies have looked mostly at ADHD medications that are central nervous system stimulants, especially methylphenidate and amphetamines.

Atomoxetine is the most widely prescribed non-stimulant for treating ADHD. It acts indirectly, by selectively inhibiting the removal of norepinephrine, a neurotransmitter that mobilizes the brain and body for action. 

To explore whether atomoxetine might be associated with any higher risk of birth defects, an international study team examined nationwide population data from four Nordic countries with universal single-payer health insurance systems – Denmark, Norway, Sweden, and Iceland – along with nationwide data from the U.S. Medicaid system, which is likewise single-payer, and covers roughly half of all births in the U.S.

They compared the prevalence of major birth defects among infants born to women exposed to atomoxetine in the first trimester (three months) of pregnancy to the prevalence among infants born to women not exposed to any ADHD drug during the period beginning three months before their last menstrual period and concluding at the end of the first trimester.

The team adjusted for maternal characteristics such as maternal age, calendar year of delivery, childbirth and medical characteristics, psychiatric conditions, high blood pressure, diabetes, kidney disease, obesity, and smoking.

In more than 2.4 million births in the four Nordic countries, and almost 1.8 million births in the U.S., there was absolutely no sign of increased prevalence of major infant malformations among infants born to mothers taking atomoxetine. 

More specifically looking at heart defects, there was again no significant association with maternal atomoxetine use, either in the Nordic population, the U.S. population, or the combined populations.

For limb malformations, there was again no significant association between maternal atomoxetine use and birth defects in the combined populations. There was an appearance of a significant association in the Nordic population, but that was based on only 5 instances, and because there were zero instances in the U.S. population, there was no net association at all in the combined population of more than 4.2 million.

The team concluded, “We found no increased prevalence of major congenital malformations overall associated with atomoxetine use in early pregnancy. The increased prevalence of limb malformations in the Nordic countries was not observed in the US. … Given the low absolute risk of both of these outcomes, these results are reassuring from a public health perspective and provide important information in the consideration of whether to continue treatment with atomoxetine during pregnancy.”

January 15, 2024

Hong Kong population study finds methylphenidate use is associated with reduced risk of fractures among persons with ADHD

Hong Kong Population Study Finds Methylphenidate Use is Associated With Reduced Risk of Fractures Among Persons with ADHD

Some animal studies and laboratory experiments have suggested that methylphenidate, the most widely prescribed pharmaceutical to treat ADHD, may weaken bones. On the other hand, other studies have indicated that methylphenidate is associated with lower risk of injury.

Some animal studies and laboratory experiments have suggested that methylphenidate, the most widely prescribed pharmaceutical to treat ADHD, may weaken bones. On the other hand, other studies have indicated that methylphenidate is associated with lower risk of injury.

What, then, is the overall effect? 

The Hong Kong Hospital Authority is the sole public health provider for the city’s 7.3 million residents. Using the Clinical Data Analysis and Reporting System, the Authority’s electronic database, an international study team set out to explore this question.

Among 43,841 individuals with ADHD medication, the team identified 2,023 children and youths 5 through 24 years old with both methylphenidate prescription and a fracture between January 2001 and December 2020. 

In the six months following prescription, individuals were found to be roughly 40% less likely to be treated for a fracture than in the six months prior to prescription. The same held true when comparing the period 7 to 12 months after prescription with the six months prior to prescription. 

As a control, the team also looked at the effect of methylphenidate prescription on a completely unrelated condition – diseases of the esophagus, stomach, and duodenum. 

In this case, there was absolutely no difference in disease incidence for equal periods of time before and after initiation of methylphenidate treatment.

The team concluded, “for all-cause fractures, the results of the … within-individual comparison demonstrated that the use of methylphenidate is associated with lower risk … compared with the … period before the treatment initiation.”

January 30, 2024

Norwegian nationwide population study finds no association between maternal organophosphate pesticide exposure and offspring ADHD

Population Study Finds No Association Between Maternal Organophosphate Exposure and Offspring ADHD

Organophosphate pesticides were originally developed as nerve agents for chemical warfare, then used in lower doses as insecticides.

Organophosphate pesticides were originally developed as nerve agents for chemical warfare, then used in lower doses as insecticides. 

Their neurotoxicity raises the possibility of effects on development of the nervous system at lower doses, including psychiatric disorders.

Previous studies have found mixed results for any association with ADHD.

Norway has a single-payer health insurance system that covers virtually the entire population, facilitating nationwide population studies. 

A primarily Norwegian study team used the Norwegian Mother, Father, and Child Cohort Study, a prospective population-based cohort that enrolled participants between 1999 and 2008 to explore possible associations. The study invited all 227,702 pregnant mothers to enroll, of which 112,908 (41%) actually enrolled.

Children were eligible for the present study if they were born after 2002, did not have Down’s syndrome or cerebral palsy, had available maternal biospecimens, were the result of a singleton pregnancy, and lived near Oslo (the location of the clinic). That left a sample of 24,035.

The team used the Norwegian Patient Registry (NPR) to identify diagnosed cases of ADHD. 

From the final eligible population, the team randomly selected 552 mother-child pairs to represent the exposure distribution in the population of pregnancies that gave rise to the cases of ADHD.

At about 17 weeks into pregnancy, maternal spot urine samples were collected at the mother’s first ultrasound appointment. These samples were then tested for concentrations of organophosphate metabolites (breakdown chemicals). 

Adjustments were made for a variety of possible confounding variables: season, birth year, maternal education, vegetable intake, fruit intake, maternal self-reported ADHD, financial status, other organophosphorus pesticides, and sex.

Comparing higher versus lower maternal exposures to organophosphates, no significant differences emerged in rates of ADHD diagnosis among offspring.

February 5, 2024

Meta-analysis reports weak evidence for mindfulness interventions for children and adolescents with ADHD

Meta-analysis Reports Weak Evidence for Mindfulness Interventions for Children and Adolescents with ADHD

Mindfulness involves focusing on the present moment. Mindfulness meditations include choosing a point of focus, such as breathing, and focusing on it continuously. They may also involve focusing single-mindedly on body movements, as in Yoga.

Mindfulness involves focusing on the present moment. Mindfulness meditations include choosing a point of focus, such as breathing, and focusing on it continuously. They may also involve focusing single-mindedly on body movements, as in Yoga. This could be potentially useful because in focusing on the present moment with attention and emotion regulation, it addresses regulatory capacities impaired in ADHD.

Previous studies of efficacy of mindfulness interventions have been inconclusive, limited by low methodological quality. A Taiwanese study team tried to remedy this with a fresh meta-analysis of randomized controlled trials (RCTs).

The team included three types of RCTs: yoga intervention, mindfulness-based psychological intervention, and mediation training. There was a lot of variation in the length of individual sessions and in the total number of hours of intervention.

Five studies used a waiting list control group. Two studies used treatment as usual or standard care as control groups. Only four studies followed best practices of using an active control group, such as a listening task, behavioral therapy, cooperative activities, or an emotional education program.

Twelve studies scored between 4 and 7 points from a possible total of 10 points, suggesting at best moderate methodological quality. More seriously, there was no indication of patient and therapist blinding.

With all these limitations, the one nominally positive result was for improvement in ADHD symptoms. A meta-analysis of seven RCTs with a combined 184 participants found a large reduction in ADHD symptoms post-treatment that did not persist at follow-up a couple months later. But between-study variation (heterogeneity) was extreme, with evidence of publication bias. The authors did not offer a revised estimate of efficacy based on the standard trim-and-fill adjustment.

Two additional meta-analyses, of seven RCTs with 200 participants, and seven RCTs with 215 participants, found no improvement in either externalizing or internalizing behaviors post-treatment. This time there was no sign of publication bias in either case. For externalizing behaviors, there was negligible heterogeneity, and moderate heterogeneity for internalizing behaviors.

A meta-analysis of four RCTs combining 122 participants found a moderate improvement in child mindfulness post-treatment, but it was not statistically significant.

February 13, 2024

Meta-analysis indicates physical activity interventions lead to major improvements in motor proficiency in children and adolescents with ADHD

Meta-analysis Indicates Physical Activity Lead to Major Improvements in Motor Proficiency in Children with ADHD

The three primary symptoms of ADHD are inattention, hyperactivity, and impulsivity, which can significantly limit personal, social, academic, or occupational functioning.

The three primary symptoms of ADHD are inattention, hyperactivity, and impulsivity, which can significantly limit personal, social, academic, or occupational functioning. 

In addition to these symptoms, between a third and a half of children and adolescents with ADHD have limited motor proficiency. They are less coordinated or skilled in performing motor tasks than their peers. This in turn reduces their participation in physical activities. They are more likely to become overweight or obese. They are also more likely to have difficulty socializing with peers.

Current ADHD medications are effective at treating the primary symptoms of ADHD, but have no known effect on impaired motor proficiency. 

Noting that “physical activity interventions are relatively easy to implement and have been shown to improve motor proficiency compared to other behavioral therapies,” a joint Chinese and American study team set out to explore effect sizes through a systematic review of the peer-reviewed medical literature.

They identified ten studies with a total of 413 participants suitable for meta-analysis. Overall, physical activity interventions led to very large effect size improvements in motor proficiency. There was no sign of publication bias, but considerable variation (heterogeneity) between studies.

To address this heterogeneity, the team next investigated how different types of physical activity intervention affected outcomes. Those that concentrated on body coordination, fine motor control (manual dexterity, using the small muscles in our hands and wrists), and object control (moving or receiving an object such as a ball with accuracy) were found to be responsible for the large effect size improvements in motor proficiency, this time with low heterogeneity.

By contrast, strength and agility training and locomotor training (such as walking, running, hopping, skipping) were associated with smaller effect size improvements that were no longer significant, and continued to vary significantly between studies.

Despite combining ten separate studies, sample sizes remained small, even more so when broken down by type of physical activity intervention. Strength and agility interventions were associated with a medium-to-large effect size improvement, but with only four studies combining 131 participants, may simply have been under-powered to achieve significance. Similarly, locomotor interventions were associated with small-to-medium effect size improvement, but with only three studies and a total of 117 participants, may again have been under-powered. 

While these preliminary findings look promising, they will need additional studies and greater numbers of total participants to be confirmed.

March 7, 2024

Nationwide population study finds no harm from in utero exposure to ADHD medication

Nationwide Population Study Finds No Harm from In Utero Exposure to ADHD Medication

Now that ADHD pharmaceuticals are among the most widely prescribed medications during pregnancy, we need to be aware of any long-term harms to offspring from in utero exposure.

Now that ADHD pharmaceuticals are among the most widely prescribed medications during pregnancy, we need to be aware of any long-term harms to offspring from in-utero exposure.

Denmark has a single-payer public health care system that encompasses virtually its entire population. Combined with national registers that track demographic as well as health data for the whole population, this makes it easy to do population-wide studies.

Availing itself of these registers, an international study team looked at all 1,068,073 single births from 1998 to 2015. It then followed all these individuals through the end of 2018, or until any developmental diagnosis, death, or emigration, whichever came first.

The team compared children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy with children of mothers who discontinued ADHD medication before pregnancy. There were 898 of the former and 1,270 of the latter in the cohort.

To reduce the influence of potential confounding variables, the team adjusted for maternal age, parity, maternal psychiatric history, in- or outpatient admission to psychiatric ward within two years prior to pregnancy and until delivery, use of other psychotropic medications during pregnancy, number of hospitalizations during pregnancy not related to psychiatry, smoking during pregnancy, living alone, education, birthyear, and psychiatric history of the father. 

Children exposed in utero to ADHD medication were found to be at no greater risk of any developmental impairment.

The timing of the exposure by trimester of pregnancy made no difference. Neither did the duration of exposure.

Neither children exposed to stimulant medications (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil) nor to non-stimulants (atomoxetine, clonidine) were at greater risk of any developmental impairment

Focusing more narrowly on specific impairments, children exposed in utero to ADHD medication were no more likely to be autistic. They were more likely to have ADHD, but the association did not reach statistical significance.

Children exposed in utero to ADHD medication were also no more likely to develop hearing or cerebral vision impairment or febrile seizures or a growth impairment. Surprisingly, they were 40% less likely to become epileptic, the only statistically significant association found in the study.

The authors concluded, “Our results are important because stimulant medications are critical for many adults, including women of childbearing age, to perform their essential functions at work, home, and school. Pregnant women who depend on stimulants for daily functioning must weigh the potential of exposing their fetus to unknown developmental risks against potential medical, financial, and other consequences to both mother and child that are associated with exacerbation of ADHD symptoms when stopping the medication, such as inability to maintain employment and unsafe driving. The present study provides reassurance that several essential categories of child outcomes that could reasonably be suspected to be affected by stimulants, including body growth, neurodevelopment, and seizure risk, do not differ based on antenatal stimulant exposure. Future studies would benefit from larger sample sizes making it possible to conduct stratified analyses on ADHD medication type.”

Study of U.S. 12th grade public and private school students finds no link between stimulant use for ADHD and subsequent cocaine or methamphetamine use

Large Scale Study of U.S. High Schoolers Finds No Link Between Stimulant Use for ADHD and Subsequent Cocaine or Methamphetamine Use

Monitoring the Future is a multicohort U.S. national longitudinal study of adolescents followed up into young adulthood.

Monitoring the Future is a multicohort U.S. national longitudinal study of adolescents followed up into young adulthood. 

The U.S. research team used data from this study to follow 5,034 twelfth graders over a period of six years, until they were 23 and 24 years of age.

Prescription stimulant misuse was assessed at baseline and each follow-up survey year by asking how often they used prescription stimulants without a physician’s orders. They were similarly asked about cocaine and methamphetamine use.

The study team adjusted for the following confounding variables: sex, race and ethnicity, parents’ level of education, urbanicity, U.S. region, cohort year, grade point average during high school, past-30-day cigarette use (at 18 years of age), past-2-week binge drinking (at 18), past-year marijuana use (at 18), past-year prescription opioid misuse (at 18), past-year prescription stimulant misuse (at 18), lifetime cocaine use (at 18), lifetime methamphetamine use (at 18), lifetime use of nonstimulant therapy for ADHD (at 18), and discontinued use of stimulant therapy for ADHD (at 18).

With these adjustments, they found that stimulant use for ADHD was in no way associated with subsequent cocaine use. In fact, it was associated with lesser odds of subsequent cocaine use, though the association was not statistically significant.

Likewise, they reported that stimulant use for ADHD was in no way associated with subsequent methamphetamine use.

On the other hand, those who used prescription stimulants without a physician’s orders were 2.6 times more likely to subsequently use either cocaine or methamphetamine.

The team concluded, “In this multicohort study of adolescents exposed to prescription stimulants, adolescents who used stimulant therapy for ADHD did not differ from population controls in initiation of illicit stimulant (cocaine or methamphetamine) use, which suggested a potential protective effect, given evidence of elevated illicit stimulant use among those with ADHD. In contrast, monitoring adolescents for PSM is warranted because this behavior offered a strong signal for transitioning to later cocaine or methamphetamine initiation and use during young adulthood.”

February 15, 2024

Two new meta-analyses evaluate digital interventions for treating ADHD

Two New Meta-analyses Evaluate Digital Interventions for Treating ADHD

There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior.

There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior. They affect reading speed and accuracy, reading comprehension, attention, and impulse control, among other behaviors important to the ability to function in social, educational, and professional environments.

A Swedish study team based at Umeå University recently conducted a systematic search of the medical literature to explore the efficacy of computerized cognitive training (CCT) to improve executive functioning in adults with ADHD.

They included published randomized controlled trials (RCTs) involving adults 18 to 65 years old with a primary diagnosis of ADHD. The controls were participants with either a passive (wait-list) or active (modified simple training) intervention.

Nine RCTs with a combined total of 285 participants met inclusion criteria. Lumping together all cognitive outcome types, meta-analysis reported a small effect size improvement that was just barely statistically significant (p = .048, with p < .05 as the boundary).

However, when separated out by individual outcome types – executive functioning, cognitive speed, general short-term memory, or ADHD symptom severity – the meta-analyses found no improvements that reached statistical significance. 

Moreover, all RCTs except one were judged as high risk of bias.

While it is possible that additional studies enlarging the pool of participants could lead to statistical significance, all effect sizes were small to begin with, which is not encouraging.

The team concluded, “Considering the small positive effect in this meta-analysis for overall cognitive outcomes, together with the lack of evidence for far transfer, practitioners and individuals with ADHD should weigh the costs (resources and time) against the benefits of training.”

A South Korean study team recently concluded the first RCT-only meta-analysis of game-based digital therapeutics (DTx).

Combining 14 RCTs with a total of 1,183 participants, they found a small effect size improvement in parent-rated attention symptoms for game-based DTx interventions over controls. Nine RCTs combining 424 participants likewise found a small effect size improvement in teacher-rated attention symptoms. Between-study variation (heterogeneity) was negligible, and there was no indication of publication bias.

Combining five RCTs with a total of 256 participants, they reported small effect size improvements in both parent and teacher-rated hyperactivity/impulsivity symptoms. But they found no improvement in hyperactivity symptoms alone, whether evaluated by parents or teachers. Heterogeneity was in all instances negligible, with no sign of publication bias. 

The team then compared game-based DTx interventions with pharmaceutical treatment. 

ADHD medications outperformed game-based DTx interventions for improvement of attention symptoms in both parent (four RCTs with a total of 128 participants) and teacher (three RCTs with 92 participants) ratings, with small-to-medium effect sizes. Medications likewise prevailed in improving hyperactivity/impulsivity symptoms, whether rated by parents or teachers, with small-to-medium effect sizes.

The team concluded, “This study is the first direct and indirect meta-analysis to compare the efficacy of game-based DTx between control and medication according to the assessor in an RCT. In conclusion, game-based DTx had a more significant effect than the control. Additionally, between medication treatment versus DTx, medication was more effective.”

March 15, 2024

Meta-analysis Offers Estimates of Global Prevalence of ADHD Among Children and Adolescents

New Meta-analysis Offers Separate Estimates of Global Prevalence of ADHD Among Children and Among Adolescents

An Iranian study team recently conducted a systematic search of the peer-reviewed medical literature to identify studies using DSM-V, DSM-IV, DSM IV-TR, and ICD10 criteria to estimate the prevalence of ADHD among children under 12, and, separately, among adolescents aged 12 through 17.

An Iranian study team recently conducted a systematic search of the peer-reviewed medical literature to identify studies using DSM-V, DSM-IV, DSM IV-TR, and ICD10 criteria to estimate the prevalence of ADHD among children under 12, and, separately, among adolescents aged 12 through 17.

Meta-analysis of 53 studies combining almost 97,000 children from every continent except Australia produced a prevalence estimate of 7.6% (with a 95% confidence range of 6.1% to 9.4%). An Iranian study team recently conducted a systematic search of the peer-reviewed medical literature to identify studies using DSM-V, DSM-IV, DSM IV-TR, and ICD10 criteria to estimate the prevalence of ADHD among children under 12, and, separately, among adolescents aged 12 through 17.

Meta-analysis of 53 studies combining almost 97,000 children from every continent except Australia produced a prevalence estimate of 7.6% (with a 95% confidence range of 6.1% to 9.4%). There was extensive variation (heterogeneity) between studies, but no indication of publication bias.

Meta-analysis of 25 studies covering a total of over 40,000 adolescents from every continent except Australia produced a prevalence estimate of 5.6% (with a 95% confidence range of 4% to 7.8%). Again, there was extensive variation (heterogeneity) between studies, but no indication of publication bias.

The authors conceded, “One of the limitations of this study is the high heterogeneity of studies in terms of age group. Since the purpose of this study was to measure the prevalence of children and adolescents separately, studies that report the prevalence of ADHD in children and adolescents combined were removed.”

June 24, 2024

Dose-dependent Association Found Between Childhood General Anesthesia and ADHD

Childhood General Anesthesia and Subsequent Diagnoses of ADHD

In December 2016, the U.S. Food and Drug Administration (FDA) warned “that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.” The FDA adds, “Health care professionals should balance the benefits of appropriate anesthesia against the potential risks, especially for procedures lasting longer than 3 hours or if multiple procedures are required in children under 3 years,” and “Studies in pregnant and young animals have shown that using these drugs for more than 3 hours caused widespread loss of brain nerve cells.”

That raises a concern that such exposure could lead to increased risk of psychiatric disorders, including ADHD.

Noting “There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children,” a South Korean study team conducted a nationwide population study to explore possible associations through the country’s single-payer health insurance database that covers roughly 97% of all residents.

The team looked at the cohort of all children born in Korea between 2008 and 2009, and followed them until December 31, 2017. They identified 93,717 children in this cohort who during surgery received general anesthesia with endotracheal intubation (a tube inserted down the trachea), and matched them with an equal number of children who were not exposed to general anesthesia.

The team matched the unexposed group with the exposed group by age, sex, birth weight, residential area at birth, and economic status.

They then assessed both groups for subsequent diagnoses of ADHD.

In general, children exposed to general anesthesia were found to have a 40% greater risk of subsequently being diagnosed with ADHD than their unexposed peers.

This effect was found to be dose dependent by several measures:

  • Duration of surgery: two-to-three-hour surgeries were associated with a 50% greater risk of subsequent ADHD, and surgeries of more than three hours with a 60% greater risk.
  • Number of exposures: two exposures were associated with a 54% increased risk, and three or more exposures with a 67% greater risk.
  • Placement in an Intensive Care Unit was associated with a 60% greater risk of ADHD.

All three measures were highly significant.

The authors concluded, “exposure to general anesthesia with ETI [endotracheal intubation] in children is associated with an increased risk of ADHD … We must recognize the possible neurodevelopmental risk resulting from general anesthesia exposure, inform patients and parents regarding this risk, and emphasize the importance of close monitoring of mental health. However, the risk from anesthesia exposure is not superior to the importance of medical procedures. Specific research is needed for the development of safer anesthetic drugs and doses.”

June 20, 2024

Stigma and ADHD

ADHD and Stigma

While ADHD is a legitimate medical condition supported by extensive scientific evidence, those diagnosed often confront various types of stigma. This stigma not only affects the person living with ADHD but also engulfs their family members, shaping their lives in ways that often go unnoticed.

ADHD (Attention Deficit Hyperactivity Disorder) is a real medical condition with lots of scientific evidence supporting it. However, people with ADHD often face stigma, which can impact them and their families in many ways. This article explores the different types of stigma related to ADHD and their effects, with insights from two important research studies.

Types of ADHD Stigma

  1. Public Stigma: This comes from society's stereotypes and negative attitudes toward ADHD. People with ADHD might face discrimination because others don't understand the condition well.
  2. Self-Stigma: Sometimes, people with ADHD internalize these negative societal attitudes. They might feel guilty, embarrassed, or think they're flawed, leading to low self-esteem, depression, and other mental health issues.
  3. Label Avoidance: To avoid stigma, some people might not seek help or deny their symptoms, which can make their ADHD worse over time.
  4. Associative Stigma: Family members and friends of those with ADHD can also face stigma. They might be judged or excluded because of their connection to someone with ADHD.

Research on ADHD Stigma

A study in Germany looked at public attitudes toward ADHD. It found that about two-thirds of people believed ADHD symptoms exist on a spectrum, and half knew someone with similar issues. However, a quarter of the people surveyed felt annoyed by someone with ADHD. While most were okay with having an adult with ADHD as a colleague or neighbor, a quarter were against renting a room to them or giving them a job recommendation. Personal experience with ADHD was linked to more understanding and acceptance.

Another study reviewed various factors contributing to ADHD stigma. It found that uncertainty about the reliability of ADHD diagnoses, perceived dangerousness of people with ADHD, socio-demographic factors, skepticism toward ADHD medication, and whether someone disclosed their diagnosis all contributed to stigma. This stigma can negatively impact treatment adherence, effectiveness, and overall well-being of those with ADHD.

Effects of Stigma on Individuals and Families

Stigma can have serious consequences for people with ADHD and their families:

  • Children: Public stigma can lead to social isolation, academic problems, and bullying.
  • Adolescents and Adults: Self-stigma can prevent them from seeking help, worsening their symptoms and mental health.
  • Families: Associative stigma can lead to parents feeling judged or blamed, causing social isolation and guilt. They also face stress advocating for their child in school and healthcare settings.

Moving Forward

Stigma creates significant barriers to treatment and quality of life for those with ADHD and their families. It's crucial to address these negative attitudes by raising awareness, sharing accurate information, and offering support. Educating healthcare providers, teachers, employers, families, and the public about ADHD can help create a more accepting environment. This way, people with ADHD and their families can live fulfilling lives without the burden of stigma.

June 17, 2024

Pair of large U.S. cohort studies find little to no evidence of association between child and adolescent ADHD and digital media screen time

Large Cohort Studies Find Little-to-No Evidence of Association Between ADHD and Digital Media Screen Time

These days, kids in America are using digital devices like smartphones, tablets, computers, and TVs more than ever. Some people worry that this might be linked to ADHD, a condition that makes it hard for kids to pay attention and control impulsive behaviors.

These days, kids in America are using digital devices like smartphones, tablets, computers, and TVs more than ever. Some people worry that this might be linked to ADHD, a condition that makes it hard for kids to pay attention and control impulsive behaviors.

Two new studies tried to find out if there's a connection between screen time and ADHD. They used data from a big survey about kids' health across the U.S. One study looked at nearly 46,000 kids aged six to 17 over two years, from 2019 to 2020. The other study analyzed data from over 101,000 kids aged zero to 17, from 2018 to 2020.

The studies figured out if a child had ADHD by asking their caregivers if a doctor or health care provider ever told them that the child had ADHD.

Findings from the First Study

The first study found that kids who used screens for two to three hours a day were 22% more likely to have ADHD. Kids who used screens for four or more hours a day were 74% more likely to have ADHD compared to kids who used screens for less than two hours a day.

However, when the researchers considered other factors like the child's age, sex, poverty status, parents' education, race, and other health problems, the link between screen time and ADHD disappeared. They did find a small link between screen time and anxiety and depression, but no link at all with ADHD.

Findings from the Second Study

The second study also considered factors that might affect the results, but they didn't look at whether the child had other behavior problems. They found that for kids five years old and under, using screens for up to three hours a day didn't make them more likely to have ADHD. But kids who used screens for four or more hours a day were twice as likely to have ADHD compared to kids who used screens for less than an hour a day.

For kids aged six to 17, those who used screens for two hours a day were 11% more likely to have ADHD. Kids who used screens for three hours a day were 16% more likely, and kids who used screens for four or more hours a day were 32% more likely to have ADHD compared to kids who used screens for less than an hour a day.

Important Points to Remember

There are two key things to keep in mind from these studies:

  1. The differences found were pretty small.
  2. The first study suggested that anxiety and depression might actually be the reason for the link between screen time and ADHD, not the screen time itself.

Conclusion

Overall, these studies didn't find strong evidence that using digital devices causes ADHD in kids and teenagers. While there might be some small connections, other factors like anxiety and depression could play a bigger role.  Also, this was not a controlled experiment.  It is an observational study that cannot rule out many factors. It is importaant to consider that having ADHD causes one to use digital devices more frequently.

Meta-analysis finds physical activity associated with improved inhibitory function

Understanding the Role of Disinhibition in ADHD and the Impact of Physical Activity

A key component of ADHD is inhibition dysfunction disorder. Inhibition function involves control of one’s attention, thought, emotions, and behavior. That enables individuals to overcome strong external temptations or internal tendencies, and become more focused.

ADHD often includes a problem called disinhibition. This means that the brain struggles to control attention, thoughts, emotions, and behavior, which can lead to negative outcomes. Normally, inhibition helps people stay focused and avoid distractions, but when it fails, it's called disinhibition.

Children with ADHD who have problems with inhibition may face issues like substance abuse, self-harm, and antisocial behavior. Improving their inhibition can help them better manage themselves, do well in school, and have better relationships.

A team of researchers from China and South Korea explored whether physical activity could improve inhibition in children with ADHD. They reviewed studies and excluded those without control groups, those with poor quality assessments, and those involving other interventions like cognitive training or supplements. Their final analysis included 11 studies with 713 participants.

Key Findings on Physical Activity

  1. Frequency and Duration: Physical activity had to be done at least twice a week to show significant improvement in inhibition. Sessions needed to last between 45 minutes to an hour for noticeable benefits, with sessions over an hour showing even greater improvements.
  2. Consistency: Regular, long-term physical activity was more effective than single sessions.
  3. Intensity: Moderate-to-vigorous activities were better than moderate activities alone.
  4. Type of Activity:some text
    • Open-skilled sports (like ping-pong or taekwondo) which involve reacting to changing environments, showed the most significant improvements.
    • Closed-skill sports (like running or swimming) showed smaller improvements.
    • Exergaming (exercise using video games) had moderate benefits.
  5. Specific Improvements:some text
    • Improvements in response inhibition (the ability to control impulsive responses) were small to medium.
    • Improvements in interference suppression (preventing distractions from affecting working memory) were large.

Conclusion

The research concluded that physical activity can significantly improve the inhibition in children with ADHD, especially with regular, moderate-to-vigorous, open-skilled exercise done at least twice a week for an hour or more. Future studies should continue to explore this with high-quality methods to confirm these findings.

June 4, 2024

Meta-analysis finds limited benefits from computerized cognitive training

Meta-analysis Finds Limited Benefits from Computerized Cognitive Training

Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.

Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.

CCT programs target one or more cognitive processes such as motor inhibition, interference inhibition, sustained attention, and working memory. They ramp up task difficulty as performance improves. The goal is to harness the brain’s inherent adaptability (neuroplasticity) to boost performance. 

A European study team that previously probed the efficacy of CCT through meta-analysis had been unable to provide a robust estimate of effect size due to an insufficient number of high-quality trials with probably blinded outcomes. Noting that “there have been a considerable number of new RCTs [randomized controlled trials] published, many with larger samples, well-controlled designs and blinded outcomes,” the team performed an updated systematic review and meta-analysis.

They included RCTs with participants of any age who either had a clinical diagnosis of ADHD or were above cut-off on validated ADHD rating scales. RCTs had to have been peer-reviewed and published in an academic journal, and to have reported a validated outcome measure of ADHD symptoms, neuropsychological processes, and/or academic outcomes.

Fourteen RCTs with a combined total of 631 participants had probably blinded outcomes. Meta-analysis of these studies yielded no significant effect on either overall ADHD symptoms or hyperactivity/impulsivity symptoms. There was a marginally significant reduction in inattention symptoms, but the effect size was small. Between-study variation (heterogeneity) was negligible and there was no sign of publication bias.

Regarding academic outcomes, meta-analyses revealed no gain in arithmetic ability or reading fluency. There was a small but not statistically significant improvement in reading comprehension. Heterogeneity was minimal, with no indication of publication bias.

With two related exceptions, meta-analyses of RCTs measuring executive functions likewise reported no significant improvements in attention, interference inhibition (initial stage in controlling impulsive behavior), motor inhibition (follow-up stage in controlling impulsive behavior), non-verbal reasoning, processing speed, and set shifting (the ability to unconsciously shift attention between one task and another).

The exceptions were for working memory tasks. Meta-analysis of 15 RCTs with a combined 753 participants reported a highly significant small-to-medium effect size improvement in verbal working memory. A separate meta-analysis of nine RCTs with a total of 441 participants similarly reported a highly significant improvement in visuospatial working memory, this time with medium effect size.

The team concluded, “There was no empirical support for the use of CCT as a stand-alone intervention for ADHD symptoms based on the largest and most comprehensive meta-analysis of RCTs conducted to date. Small effects, of likely limited clinical importance, on inattention symptoms were found – but these were limited to the setting in which the intervention was delivered. Robust evidence of small- to-moderate improvements in visual-spatial and verbal STM/WM tasks did not transfer to other domains of executive functions or academic outcomes.”

Population Study Finds Reductions in Crime Rates Among Persons with ADHD Receiving Pharmacological Treatment

Population Study Finds Reductions in Violent and Public Order Crime Rates Among Persons with ADHD Receiving Pharmacological Treatment

Norway has a single-payer health insurance system that covers virtually the entire population and is linked to a series of national registries tracking all sorts of data including criminal records.

Norway has a single-payer health insurance system that covers virtually the entire population and is linked to a series of national registries tracking all sorts of data including criminal records.

Using this data, a study team identified all 5,624 persons aged 10 to 18 diagnosed with ADHD between 2009 and 2011. It tracked their use of ADHD medication, and subsequent criminal charges. 

Filled prescriptions were primarily for stimulant methylphenidate (90%) and the nonstimulant atomoxetine (9.5%). They tracked the cumulative number of daily defined doses (DDD) filled for any ADHD prescriptions following ADHD diagnosis. 

They also compared this group with a general population sample of persons aged 10 to 18 without contact with mental health services, matched on age, sex, and geography.

They adjusted for the following confounders: age, sex, year of contact with clinic, psychiatric comorbidity at time of diagnosis, country of birth, charges before ADHD diagnosis, parents’ marital status, parent’s highest education when the child was 6 years, and parent’s labor income when the child was 6 years. 

They further adjusted for municipality-level population size and high school dropout rates, and the following aggregated measures from the random sample of the general population: municipality-level labor income of parents and clinic-level percent of youth crime, youth immigrants, mothers’ marriage rate, and parents’ education level.

Comparing persons with ADHD to the matched general population over eight years follow-up, those with ADHD had considerably higher rates of criminal charges:

  • 2.7 times more likely to be charged with any crime.
  • 6 times more likely to be charged with a violent crime.
  • 7 times more likely to be charged with a sexual offense (though only among males)
  • 4 times more likely to be charged with property crimes.

Next the team examined outcomes of pharmaceutical treatment.

Comparing persons with ADHD undergoing pharmacological treatment with those not receiving such treatment, those undergoing treatment had lower rates of certain criminal charges. At two years follow-up, those treated had 7.3% less violence-related charges. This corresponds to a number needed to treat (NNT) estimate of 14, indicating that on average treating 14 patients for two years avoids one violence-related criminal charge. Pharmacological treatment reduces public-order charges by at four years follow-up by 15.4% (NNT = 7), and any crime at three years follow-up by 18.5% (NNT = 5).

The authors noted, “Violence and public-order crimes are often caused by reactive-impulsive behavior which is more common in ADHD,” and concluded, “this is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment, while no effects were found in crimes requiring criminal intent, conspiracy, and planning.”

May 9, 2024

Meta-analysis finds no link between maternal exposure to PFAS and offspring ADHD

Meta-analysis Finds No Link Between Maternal Exposure to PFAS and Offspring ADHD

Perfluoroalkylated substances (PFASs) – often described in the popular press as “forever chemicals” – are highly persistent pollutants.

Perfluoroalkylated substances (PFASs), commonly known as "forever chemicals" in the media, are pollutants that do not break down in the environment. Their chemical structure includes fluorine atoms bonded to carbon, which makes them effective at repelling water. This property has led to their use in water-repellent clothing, stain-resistant carpets and furniture, and nonstick cookware.

However, the same chemical structure that makes PFASs useful also makes them a concern for human and animal health, as there are no natural biological processes to remove them from the body. Once ingested, they accumulate and become more concentrated at each level of the food chain. PFASs can also cross the placental barrier, raising concerns about potential harm to developing embryos and fetuses.

A Chinese research team conducted a systematic review of the medical literature to examine if there is a link between maternal exposure to PFASs and an increased risk of ADHD in children. They analyzed data from several studies:

- A meta-analysis of five studies involving 2,513 mother-child pairs found no increase in ADHD risk from exposure to PFOA (perfluorooctanoate) or PFOS (perfluorooctane sulfonate). The consistency across these studies was high, with little variation and no evidence of publication bias.

- Another meta-analysis of three studies with 995 mother-child pairs also showed no increase in ADHD risk from exposure to PFNA (perfluorononanoate) or PFHxS (perfluorohexane sulfonate), with similarly negligible variation between studies and no publication bias.

- In an analysis comparing the highest and lowest quartiles of maternal exposure, a slight increase in ADHD risk was observed with PFOA exposure, while a slight decrease was noted with PFOS exposure. Both findings were marginally significant and may be due to the small sample sizes. 

The researchers concluded that more studies are needed to confirm these findings due to the limited evidence available.

May 6, 2024

Meta-analysis confirms association between overweight mothers and ADHD in offspring

Meta-analysis Confirms Association Between Overweight Mothers and ADHD in Offspring

Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.

Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.

Further noting that previous meta-analyses have suggested a link between maternal obesity and increased risk of ADHD in offspring, they set out to also look at paternal obesity.

Only two studies, however, probed the relationship between paternal overweight and obesity and offspring ADHD, making that meta-analysis impractical. A meta-analysis of six studies with a combined total of over a hundred thousand participants found no significant association between overweight or obsess fathers and offspring mental disease of any kind (with all such disorders lumped together). There was no indication of publication bias and little variability (heterogeneity) between studies.

Ten studies with a combined total of over 800,000 participants, however, examined the relationship between overweight and obese mothers and offspring ADHD. Overweight mothers were twenty percent more likely to have offspring with ADHD. Obese mothers were more than fifty percent more likely to have offspring with ADHD. There was absolutely no sign of publication bias in either case. Inter-study heterogeneity was negligible for overweight, and moderate for obesity.

The team concluded, “We found that the most recent evidence indicates the detrimental connections between parental pre-pregnancy overweight/obesity and offspring mental health.” That is perhaps a bit overstated, as the only clear sign was with maternal overweight or obesity.

April 22, 2024

Inequities in ADHD diagnosis in the United States

Inequities in ADHD diagnosis in the United States

A transcontinental study team (California, Texas, Florida) used a nationally representative sample – the 2018 National Survey of Children’s Health – to query 26,205 caregivers of youth aged 3 to 17 years old to explore inequities in ADHD diagnosis.

A transcontinental study team (California, Texas, Florida) used a nationally representative sample – the 2018 National Survey of Children’s Health – to query 26,205 caregivers of youth aged 3 to 17 years old to explore inequities in ADHD diagnosis.  

With increasing accessibility of the internet in the U.S., more than 80% of adults now search for health information online. Recognizing that search engine data could help clarify patterns of inequity, the team also consulted Google Trends.

The team noted at the outset that “[d]ocumenting the true prevalence of ADHD remains challenging in light of problems of overdiagnosis (e.g., following quick screening rather than full evaluation incorporating multi-informant and multi-method data given limited resources) and underdiagnosis (e.g., reflecting inequities in healthcare and education systems).” Underdiagnosis is known to be influenced by lack or inadequacy of health insurance, inadequate public health funding, stigma, sociocultural expectations in some ethnic groups, and structural racism, among other factors.

After controlling for poverty status, highest education in household, child’s sex, and child’s age, the team reported that Black youth were a quarter (22%) less likely to receive ADHD diagnoses than their white peers. Latino/Hispanic youth were a third (32%) less likely and Asian youth three-quarters (73%) less likely to receive ADHD diagnoses than their white peers.

The team also found that state-level online search interest in ADHD was positively associated with ADHD diagnoses, after controlling for race/ethnicity, poverty status, highest education in household, child’s sex, and child’s age. However, the odds ratio was low (1.01), “suggesting the need for additional evaluation.” Furthermore, “There was no interaction between individual-level racial/ethnic background and state-level information-seeking patterns. … the state-level online information-seeking variation did not affect the odds that youth of color would have a current ADHD diagnosis over and above other included characteristics.” 

That could be due in part to the gap in high-speed broadband access between Black and Hispanic in contrast to white populations, but that would not explain the even larger gaps in diagnosis for Asian youth, who tend to come from more prosperous backgrounds.

The team concluded, “Persistent racial/ethnic inequities warrant systematic changes in policy and clinical care that can attend to the needs of underserved communities. The digital divide adds complexity to persistent racial/ethnic and socioeconomic inequities in ADHD diagnosis …”

Meta-analysis suggests ADHD contributes significantly to alcohol use disorder in persons with comorbid bipolar disorder

Meta-analysis suggests ADHD contributes significantly to alcohol use disorder in persons with comorbid bipolar disorder

Bipolar disorder is a severe mental illness that afflicts over one in fifty persons worldwide. About a quarter of those with bipolar disorder also has alcohol use disorder (AUD). This in turn complicates the treatment of their bipolar disorder. It exacerbates their symptoms, makes them more likely to be suicidal, and increases the risk of hospitalization.

More than one in five persons with bipolar disorder also have ADHD, which is likewise known to be correlated with AUD. To what extent does ADHD contribute to AUD in persons with comorbid bipolar disorder?

A European study team recently conducted a systematic search of the peer-reviewed medical literature to address that question. The team identified eleven studies with a combined total of 2,734 participants that could be aggregated to perform a meta-analysis.

They found that persons with comorbid ADHD and bipolar disorder were two and a half times more likely to be diagnosed with alcohol use disorder than persons with bipolar disorder but no ADHD.

Between-study heterogeneity was negligible, and there was no sign of publication bias.

The authors concluded, "At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship."

March 13, 2022

Is Oxytocin During Childbirth an ADHD Risk Factor Later in Life?

Danish-Finnish countrywide population studies conclude that administration of oxytocin during childbirth is not a risk factor for ADHD

Oxytocin is a hormone released by the pituitary gland that stimulates the contraction of the uterus during labor. Synthetic oxytocin is widely administered during labor to supplement a birthing parent's supply and facilitate childbirth.

Previous studies have found an association between synthetic oxytocin and increased odds of ADHD in offspring.

A joint Danish and Finnish team used their countries' national registers to obtain countrywide cohorts encompassing over 577,000 Danes and over 945,000 Finns. Oxytocin had been administered in 31% of the Danish deliveries and 46% of the Finnish ones. Any children either diagnosed with ADHD or who received prescriptions for ADHD drugs were categorized as having ADHD.

As in previous studies, unadjusted results found a significant association with ADHD. Combining the two populations, children whose mothers had received oxytocin during labor were 16% more likely to later develop ADHD.

After adjusting for a series of confounders such as birth year, maternal age, education, marital status, parity, smoking in pregnancy, labor induction, gestational age, and intrauterine growth, the association dropped markedly, to an increased likelihood of barely 3%.

Looking at Denmark alone, the unadjusted risk was 9% greater, vanishing altogether after adjusting for confounders. In Finland, the unadjusted risk was 20% greater, declining to 4% after adjusting for confounders.

The authors noted that "Exposure to obstetric oxytocin is not a random process, and it is likely that other factors than the ones included here vary systematically between women treated vs not treated with oxytocin. ... Therefore, we find it most likely that the minor elevations in risk are due to uncontrolled and residual confounding, and thereby our results underscore the lack of a causal association between obstetric oxytocin exposure and ADHD."

February 1, 2022

Breastfeeding associated with an almost 2/3 reduction in risk of ADHD

Breastfeeding associated with an almost 2/3 reduction in risk of ADHD

Preschool children who were never breastfed as infants are much more likely to have a medical diagnosis of ADHD than are children who were exclusively breastfed as infants.

The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for the first six months of infancy and continuation of breastfeeding for at least a year thereafter. Yet less than a third of U.S. mothers are still breastfeeding their infants at 12 months.

Previous studies have suggested that breastfeeding is associated with a lower risk of ADHD. But sample sizes have been small, and have not sufficiently explored confounding factors.

Using the Centers for Disease Control and Prevention's 2011-2012 National Survey of Children's Health, a research team analyzed data from a representative U.S. sample of 12,793 three- to five-year-old children.

The team excluded children with autism, developmental delays, speech problems, Tourette syndrome, epilepsy or seizure disorder, hearing problems, non-correctable vision problems, bone/joint/muscle problems, brain injury/concussion, or any current behavioral/conduct problems other than ADHD.

The team also adjusted for potential confounders. Some were demographic: sex, age, race, household income, the number of adults older than 18 years of age living in the home, and the number of children younger than the age of 18 years living in the home. Other variables related to health care access and delivery: insurance type, consistency of health insurance in the past 12 months, and a composite variable reflecting having a primary care provider, getting needed referrals, and effective care coordination. Exposure to secondhand smoke and preterm births were other key variables.

In the fully adjusted results, children who had been breastfed for at least six months were 62% less likely to be diagnosed with ADHD than those who had not (p = .0483). Moreover, each month of breastfeeding duration was associated with a significant additional 8% reduction in the odds of an ADHD diagnosis (95% confidence interval from 1% to 14%).

The authors concluded, "Preschool children who were never breastfed as infants were much more likely to have a medical diagnosis of ADHD than were children who were exclusively breastfed. Moreover, there seems to be a continuum of neuroprotective benefits associated with breastfeeding duration. Although these analyses cannot establish a causal relationship, our findings add to a growing body of literature-including several longitudinal studies and a meta-analysis-that suggests breastfeeding may reduce the likelihood of a child having later problems with inattention and/or hyperactivity. Although follow-up studies are needed to further examine the relationship between infant feeding and ADHD, these findings provide evidence to support the neurodevelopmental benefits of breastfeeding."

January 28, 2022

Is Antibiotic Use in Infancy a Risk-Factor for ADHD? How Do We Know?

Nationwide twin cohorts in the Netherlands and Sweden suggest antibiotic use in infants is not a risk factor for ADHD

There was no association found between ADHD and ASD diagnoses and early antibiotic use when environmental and genetic family factors were taken into account.

Proper development of the gut biota is important for the health of the brain and nervous system. It has been hypothesized that disturbances of gut bacteria by antibiotics could contribute to the development of neurodevelopmental disorders, including ADHD.

In the case of ADHD, studies to date have produced conflicting results. To tease out any familial confounding reflecting shared environment and genetics, a joint Dutch-Swedish team of researchers further tested the hypothesis through 7- to 12-year-old twins in the Netherlands Twin Register (25,781 twins) and 9-year-old twins in the Swedish Twin Registry (7,946 twins).

ADHD symptoms in the Netherlands cohort were derived from mothers' answers to the short Conners' Parental Rating Scale-Revised. For the Swedish cohort, ADHD was determined through the International Classification of Diseases codes for ADHD in the cross-linked National Patient Register.

Exposure to antibiotics during the first two years of childhood was determined by parent reports for the Netherlands twin cohort, and by prescription claims for antibiotics in the Swedish twin cohort.

Covariates were explored in both twin cohorts including educational attainment of parents, gender of the infant, birth weight, delivery mode, and asthma. Breastfeeding was also explored in the Dutch cohort.

In the unmatched analysis, comparing children with ADHD with non-related children without ADHD, early-life antibiotic use was associated with a significant 8% greater odds of ADHD in the Netherlands cohort and a significant 14% greater odds of ADHD in the Swedish cohort.

However, when limiting the analysis to matched monozygotic twins, the association disappeared altogether in both the Dutch and Swedish cohorts. Pooling both cohorts resulted in the same outcome. In all three cases, the odds flipped into a mildly negative association, but with no statistical significance.

Using higher cutoff values for ADHD symptoms made no difference.

The authors concluded, "In this large co-twin study performed in two countries, early-life antibiotic use was associated with increased risk of ADHD and ASD, but the results suggest that the association disappeared when controlled for shared familial environment and genetics, indicating that this association may be susceptible to confounding. Our results indicate that there is no association between ADHD and ASD diagnoses and early antibiotic use when environmental and genetic family factors are taken into account."

January 24, 2022

Population Study Finds Association Between ADHD and Obesity in Adolescents

Israeli nationwide population study finds association between ADHD and obesity in adolescents

After noting that the association between ADHD and obesity has been called into question because of small sample sizes, wide age ranges, self-reported assessments, and inadequate attention to potential confounders, an Israeli study team set out "to assess the association between board-certified psychiatrist diagnoses of ADHD and measured adolescent BMI [body mass index] in a nationally represented sample of over one million adolescents who were medically evaluated before mandatory military service."

The team distinguished between severe and mild ADHD. It also focused on a single age group.

All Israelis are subject to compulsory military service. In preparation for that service, military physicians perform a thorough medical evaluation. Trained paramedics recorded every conscript's height and weight.

The study cohort was divided into five BMI percentile groups according to the U.S. Centers for Disease Control and Prevention's BMI percentiles for 17-year-olds, and further divided by sex: <5th percentile (underweight), 5th-49th percentile (low-normal), 50th-84th percentile (high normal), 85th-94th percentile (overweight) and ≥95th (obese). Low-normal was used as the reference group.

Adjustments were made for sex, birth year, age at examination, height, country of birth (Israeli or other), socioeconomic status, and education level.

In the fully adjusted results, those with severe ADHD were 32% more likely to be overweight and 84% more likely to be obese than their typically developing peers. Limiting results to Israeli-born conscripts made a no difference.

Male adolescents with mild ADHD were 24% more likely to be overweight, and 42% more likely to be obese. Females with mild ADHD are 33% more likely to be overweight, and 42% more likely to be obese. Again, the country of birth made no difference.

The authors concluded, that both severe and mild ADHD was associated with an increased risk for obesity in adolescents at the age of 17 years. The increasing recognition of the persistence of ADHD into adulthood suggests that this dual morbidity may have a significant impact on the long-term health of individuals with ADHD, thus early preventive measures should be taken.

January 6, 2022

How Effective is Cognitive Training for Preschool Children?

How effective is cognitive training for preschool children?

Further study is needed, but meta-analysis shows small, but not insignificant, effects of pre-school interventions on core executive functions.

A German team of researchers performed a comprehensive search of the medical literature and identified 35randomized controlled trials (RCTs) published in English that explored this question. Participating children were between three and six years old. Children with intellectual disabilities, sensory disabilities, or specific neurological disorders such as epilepsy were excluded.

The total number of participating preschoolers was over three thousand, drawn almost exclusively from the general population, meaning these studies were not specifically evaluating effects on children with ADHD. But given that ADHD results in poorer executive functioning, evidence of the effectiveness of cognitive training would suggest it could help partially reverse such deficits.

RCTs assign participants randomly to a treatment group and a group not receiving treatment but often receiving a placebo. But RCTs themselves vary in risk of bias, depending on:

  • whether the control condition was passive (i.e. waiting list or no treatment) or active/sham (an activity of similar duration and intensity to the treatment condition)
  • whether the outcome was measured by subjective rating (e.g. by questionnaires, susceptible to reporting biases) or more objective neuropsychological testing;
  • whether the assessment of outcome was by blinded assessors unaware of participants' treatment conditions;
  • whether there was a risk of bias from participants dropping out of the trial.

After evaluating the RCTs by these criteria, the team performed a series of meta-analyses.

Combining the 23 RCTs with over 2,000 children that measured working memory, they found that cognitive training led to robust moderate improvements. Looking only at the eleven most rigorously controlled studies strengthened the effect, with moderate-to-large gains.

Twenty-six RCTs with over 2,200 children assessed inhibitory control. When pooled, they indicated a small-to-moderate improvement from cognitive training. Including only the seven most rigorously controlled studies again strengthened the effect, boosting it into the moderate effect zone.

Twelve RCTs with over 1,500 participants tested the effects of cognitive training on flexibility. When combined, they pointed to moderate gains. Looking at only the four well-controlled studies boosted the effect to strong gains. Yet here there was evidence of publication bias, so no firm conclusion can be drawn.

Only four studies with a combined total of 119 preschoolers tested the effects on ADHD ratings. The meta-analysis found a small but non-significant improvement, very likely due to insufficient sampling. As the authors noted, "some findings of the meta-analysis are limited by the insufficient number of eligible studies. Specifically, more studies are needed which use blinded assessments of subjective ratings of ADHD ... symptoms ..."

The authors concluded that their meta-analyses revealed significant, mostly medium-sized effects of the preschool interventions on core EFs [executive functions] in studies showing the low risk of bias."

January 2, 2022

Youth ADHD is associated with elevated risks of subsequent psychotic disorder

Youth ADHD is associated with elevated risks of subsequent psychotic disorder

A French team of physicians conducted a systematic search of peer-reviewed literature to conduct a meta-analysis to examine the relationship between childhood ADHD and subsequent psychotic disorders.

What relationship, if any, might there be between childhood ADHD and subsequent psychotic disorders? Previous epidemiological studies have produced conflicting results.


A French team of physicians conducted a systematic search of the peer-reviewed literature to conduct a meta-analysis to examine this question in greater depth.
They pooled twelve studies with a combined total of 1.85 million participants, consisting of 124,095 with ADHD and just over 1.72 million controls.


The psychotic disorders analyzed included schizophrenia, schizophreniform disorder, schizotypal personality disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, and psychotic disorder not otherwise specified. These disorders had to be diagnosed after the diagnosis of ADHD in children and adolescents under 18 years old.


The meta-analysis found that persons diagnosed in childhood or adolescence with ADHD were well over four times more likely to have subsequent diagnoses of psychotic disorders than those without a diagnosis of ADHD. Limiting the meta-analysis to the six studies that were adjusted for confounders produced an identical result.


There were no statistically significant between-group differences for subgroup analyses comparing psychotic disorder or schizophrenia outcomes, cohort or case-control study design, and adjusted or unadjusted estimates. There were no significant differences between males and females.


Heterogeneity among studies was moderate (43%), and there was no sign of publication bias. Removing one study reduced heterogeneity to low levels (18%), while very slightly raising the odds of subsequent diagnosis of psychotic disorder. Looking only at the more restrictive diagnosis of schizophrenia also made no difference in the odds.


No matter how the data were analyzed, in all instances, the odds of subsequent diagnosis of psychotic disorder rose well over fourfold for those diagnosed with ADHD in their youth.


The authors concluded, "To improve our knowledge, further cohort studies should be conducted. Ideally, these studies would ensure a sufficiently long follow-up to account for the mean age at which P [psychotic disorders] develop. Such studies should consider the use of psychostimulants and the role of SUD [substance use disorder] in the causal path between ADHD and PD."

December 25, 2021

Youths with ADHD May Face Higher Risk of Injury From Unintentional Falls

American youths with ADHD face elevated risks of serious harm from unintentional falls

A team of Stanford researchers examined data from the Nationwide Emergency Department Sample to determine just how strong the association between injury from unintentional falls and ADHD is.

In the five years from 2006 through 2010, the child falls led to 11,535 head injuries in the United States, costing a billion dollars to treat. Previous studies have shown that persons with ADHD were more prone to accidental falls than normally developing individuals. Just how strong is that association among American youth?

A team of Stanford University researchers examined data for falls among youths under 18 years old from the Nationwide Emergency Department Sample (NEDS), covering 953 hospitals in 36 states between 2010 and 2015. These included falls from stairs, ladders, or scaffolding; falls from buildings or other structures; falls into holes; other falls from one level to another; falls on the same level from collisions, pushing, shoving, slipping, tripping, or stumbling.

Out of almost 49 million injuries involving youths recorded by hospital emergency departments in the NEDS from 2010 to 2015, there were 13,217,237 million falls, 139,642 of which involved youths 5-17 years old with ADHD only. These were compared with almost 7.8 million involving youths 5-17 years old with developmental disabilities.

The team adjusted for the following covariates to reduce confounding: age category, sex, income, payment source, developmental disability status, and mechanism of fall.

Youths with ADHD were found to be roughly 75% more likely than normally developing youths to be admitted for unintentional falls in hospital emergency departments. They were about 60% more likely to be admitted for hospital stays exceeding two days. They were almost twice as likely to require surgery. And they were four times as likely to require intubation through the mouth and into the airway to be placed on a ventilator to assist with breathing.

These outcomes are not surprising, given that a large proportion of youths with ADHD are prone to be more inattentive and/or impulsive on average than their normally developing peers. But they underscore the need for parents and physicians to take preventive action to reduce the chance of harm.

The authors "suggest that practitioners who provide care for children with ADHD spend extra time on educating parents regarding the increased risk of falls, especially among older children, to decrease the odds of worse outcomes from unintentional falls."

December 23, 2021

Parents of Children With ADHD at Higher Risk for Traumatic Injury

Nationwide population study finds higher risk of traumatic injury among parents of children with ADHD

Previous population studies have shown that children with ADHD have a much higher risk of traumatic injuries than their normally developing peers, and that such risk can be greatly reduced with methylphenidate treatment.

But what about the parents of children with ADHD? How does their risk compare with that of parents of normally developing children?

Taiwan has a single-payer public health insurance system that maintains comprehensive healthcare records of virtually every resident.

A Taiwanese research team availed itself of the Taiwan Maternal and Child Health Database, which covers 99.8% of all births, to identify 81,401 fathers and 87,549 mothers who had at least one offspring with ADHD and 1,646,100 fathers and 1,730,941 mothers with no offspring with ADHD.

The team determined children's ADHD status based on either an inpatient diagnosis or four or more  diagnoses.

It looked for parental traumatic injuries including burn injury, fracture, and traumatic brain injury.

To address covariates, it adjusted for age, urbanicity, low-income level, and competing risk of death.

Adjusted for those covariates, parents of children with ADHD were 20% more likely to suffer bone fractures, 27% more likely to have traumatic brain injuries, and 30% more likely to have burn injuries requiring medical treatment than parents of normally developing children.

The elevated risks were significant across the board, but roughly twice as much s for mothers as for fathers of children with ADHD - up 30% vs 15% for bone fractures, up 35% vs 23% for burn injuries, and up 45% vs 21% for traumatic brain injuries.

The authors noted that ADHD is highly heritable and that the findings may in part point to undiagnosed adult ADHD.

Another contributing factor, they suggested, is that "studies have revealed that a high proportion of parents having children with ADHD experience depression and anxiety. Stress-related negative emotions (depression and anxiety) were shown to cause loss of concentration, thereby increasing the likelihood of accidental events such as traffic accidents and contributing to the increased risks of traumatic injury among parents of children  ADHD."

The much-higher elevated risk for mothers seems to support this hypothesis, because mothers continue to be the principal caregivers in Taiwan, and are thus more exposed to the behaviors of their children. The authors cited a study indicating that "diagnosis of ADHD for children was reported to be a predictor of increased caregiver burden."

They concluded, "Given that knowledge is fundamental to act, it is essential to educate the parents of children with ADHD on the increased risk of traumatic injuries they may have. ... The need for behavioral and pharmacological intervention in parents of children with ADHD should be evaluated, especially in the parents with undiagnosed ADHD or sub-threshold ADHD symptoms. It deserves further prospective studies with longer follow-up periods to explore whether undiagnosed ADHD, care burden of parents, and children's aggressive behaviors contribute to the increased risks of traumatic injuries in parents of children with ADHD."

December 7, 2023

Swedish countrywide population study concludes that neonatal jaundice is not tied to ADHD

Swedish countrywide population study concludes that neonatal jaundice is not tied to ADHD

Bilirubin is an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile. Elevated levels in blood serum can cause jaundice, a yellowing of the skin, or whites of the eyes.

More than one in twenty Swedish newborns are treated for neonatal jaundice, which is particularly common among preterm babies. It is usually benign.

A team of Swedish researchers used e Swedish Medical Birth Register, which contains information on all children born in the country, to identify all 814,420 single births without birth defects between 1992 and 2000, and followed them until 2009. They then identified instances of neonatal jaundice and of ADHD through linked nationwide medical registers.

The team also identified a sub-sample of full siblings (384,290 children from 181,354 families) in order to control for shared familial traits.

In the unadjusted results, children with any kind of neonatal jaundice were 38% more likely to be diagnosed with ADHD. After adjustment for known confounding variables, two-thirds of the association disappeared, with a residual increased risk of 13%.

There are, however, two types of neonatal jaundice: hemolytic and non-hemolytic. Hemolytic jaundice is typically caused by the mother's immune system mistaking the fetus' red blood cells as a threat, and responding by attacking with antibodies, rupturing and destroying the cells.

The study found no association between hemolytic jaundice and ADHD, either in the raw results or after adjusting for known confounders. Unsurprisingly, there was also no association in the sibling comparison.

That meant that all the association was concentrated among children born with non-hemolytic jaundice, who in the crude results were 43% more likely to subsequently develop ADHD. Adjusting for known confounders again reduced the association by two-thirds, to 14%. But among siblings, that association vanished altogether. Children born with non-hemolytic jaundice were no more likely than their non-jaundiced siblings to develop ADHD.

The authors concluded that "neonatal jaundice is not likely a causal risk factor for ADHD."

December 14, 2023

Meta-analysis Finds Narrative Language Impairment in Youths with ADHD

Meta-analysis Finds Narrative Language Impairment in Youths with ADHD

Youths with ADHD are known to be more prone to language problems when compared with typically developing peers. To what extent does that affect their ability to share a narrative with others?

A Danish research team conducted a systematic review and meta-analysis of the peer-reviewed medical literature to explore this question. They stressed that this ability is important because "a narrative is a genre of discourse - a form of social communication used to derive meaning from experiences and to construct a shared understanding of events. In other words, it is the fundamental ability of orally producing a coherent story." They focused on the production of narratives rather than comprehension.

Studies had to have a minimum of 10 participants. They had to compare aspects of oral narrative production in children and adolescents with either a formal ADHD diagnosis or a score above a clinical cut-off on a validated ADHD rating scale to a control group of typically developing youths. Youths with confirmed autism spectrum disorder (ASD) or language impairment diagnoses were excluded. There were no constraints on IQ.

The team found sixteen studies with a combined total of 1,015 youths that met these criteria and were suitable for meta-analysis.

They examined seven aspects of oral narrative production:

·        Coherence: A story structure that is logical and easy to follow in cause and sequence. There is a clear beginning, middle, and end. There are goals, attempts, and outcomes. A meta-analysis of nine studies with a combined total of 750 participants found youths with ADHD less coherent than their typically developing peers, with a medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
·        Cohesion: This ensures referencing of events and characters in a manner that enables the listener to grasp how characters, events, and ideas in a story are related. Ambiguous or contradictory references get in the way of this. A meta-analysis of eight studies with a combined total of 501 participants found youths with ADHD showed less cohesion than their typically developing peers, with a medium effect size. Again, with virtually no between-study heterogeneity, and no sign of publication bias.
·        Disruptions: These can be sequence errors, misinterpretations, embellishments, or confabulations - fabricating imaginary experiences as compensation for loss of memory. A meta-analysis of six studies with 389 participants found youths with ADHD had more disruptions than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bias.
·        Fluency: Best explained in terms of errors that interfere with this quality, such as false starts, repeating words or sentences, and abandoning sentences without completing them. A meta-analysis of four studies with 220 participants found no difference in fluency between youths with ADHD and their typically developing peers.
·        Production: This is a measure of output -overall length of the story, number of sentences, number of words. After adjusting for evidence of publication bias, a meta-analysis of twelve studies with 645 participants found no difference here.
·        Syntactic complexity: This includes the extent of vocabulary and the use of proper grammar. A meta-analysis of six studies with 272 participants found youths with ADHD displayed less syntactic complexity than their typically developing peers, with a small-to-medium effect size. There was virtually no between-study heterogeneity and no sign of publication bi
·        Internal state language: References to perceptions, thoughts, beliefs, and feelings. There were only two studies with 130 participants, so no meta-analysis was performed.

The authors concluded, "the results from the current meta-analysis suggest that children with ADHD have impairments in their narrative language. In particular, children with ADHD produce narratives that are less coherent, less cohesive, less syntactically complex, and include more disruptive errors than typically developing children do."

December 4, 2023

A nationwide population study examines sleep problems in youth with ADHD

A nationwide population study examines sleep problems in youth with ADHD

Denmark has a universal health insurance system that requires tracking all health care data in a system of national registries. That makes it possible to explore what's going on in an entire national population, rather than have to rely on sampling a small part of it, and hoping the sampling is reasonably representative.

A team of Danish researchers used the Civil Registration System to identify all single births through 1993 through 2014 and linked those records to corresponding records in the Psychiatric Central Research Register and National Patient Register for the years 2011through 2016. There were 1,397,850 youths in that cohort, of whom 12,844 were diagnosed with ADHD during the study period.

At five years of follow-up after diagnosis, almost three in ten youths with ADHD (29 percent) had registered evidence of sleep problems (including the use of melatonin, which is by prescription only in Denmark). For those with concomitant conduct disorder, almost half (45 percent) had registered evidence of sleep problems.

In the general population, on the other hand, the cumulative risk of sleep problems at five years of follow-up varied from one in a hundred for children followed from age 5 or age 10 to one in forty for those followed from age 15.

After adjusting for the confounding effects of three other neurodevelopmental disorders - autism spectrum disorder, oppositional defiant disorder/conduct disorder, and epilepsy­- youths with ADHD were still roughly 23 times more likely to have sleeping problems than were normally developing youths.

The authors cautioned, however, that the low rate of sleep problems in the general population "may indicate that sleeping problems without coexisting neurodevelopmental disorders are generally diagnosed or treated in primary health care (and hence not included in our study)."

A further limitation, they added, is that "we can not exclude the possibility of residual confounding. Thus, it remains unclear whether neurodevelopmental disorder contributes to the sleep problem or whether certain unmeasured characteristics of children with neurodevelopmental disorders may explain the apparent association with sleep problems."

September 27, 2023

Meta-analysis Finds Association Between Postnatal Secondhand Smoke and ADHD

Meta-analysis finds association between postnatal secondhand smoke and ADHD

Secondhand smoke (SHS) is tobacco smoke inhaled by nonsmokers sharing enclosed spaces with smokers. It contains well over two hundred toxic chemicals, including some toxic metals known to cause serious harm to humans. It is among the most common indoor air pollutants worldwide, with roughly two in five children exposed.

Until now, studies have focused primarily on maternal smoking before childbirth. A Chinese research team set out to explore what, if any, association there might be between childhood exposure to SHS and ADHD. They conducted a comprehensive search of the peer-reviewed literature and identified nine studies with a combined total of over a hundred thousand participants that looked for such effects. The studies were carried out in the United States, Germany, Spain, and the Republic of Korea.

Merging these studies into a meta-analysis, the team found that children exposed to secondhand smoke were 60 percent more likely to develop ADHD. The same overall pattern held true on all three continents.

A further meta-analysis of four of the studies with over 12,000 participants found children exposed to secondhand smoke were 33% more likely to exhibit conduct problems.

The authors concluded, "The results of our meta-analysis suggest that postnatal exposure to SHS may be associated with ADHD in children. Exposure to SHS can also lead to a variety of adverse behavioral outcomes in children. Therefore, parents should stop smoking to create a good growing environment for their children. Further prospective studies should fully adjust for potential confounding factors to determine whether there is a causal relationship between SHS and ADHD."

December 4, 2023

Why are children born in August more likely to be diagnosed with ADHD?

Why are children born in August more likely to be diagnosed with ADHD?

Taiwan's single-payer National Health Insurance system encompasses its entire population, and it's National Health Insurance Research Database tracks all medical claims in the system. That makes it easy to conduct nationwide population studies.

Two Taiwanese research teams availed themselves of that database to explore in-depth a surprising relationship between the birth month of children and rates of ADHD diagnosis.

In principle, the two should be unrelated. The likelihood of diagnosis should be the same regardless of the month a child is born. But the data are clear that this is not so. Children born late in summer are the most likely to be diagnosed with ADHD, and those in autumn are the least likely.

Using a nationwide database of over 29 million persons, one of the teams (Hsu et al.) found that children born in April were 6% more likely to be diagnosed with ADHD than the year-round mean, those in May 12% more likely, those in June 20% more likely, and those in July and August well over 25% more likely.

Conversely, children born in September were 19% less likely to be diagnosed with ADHD than the year-round mean, followed by a gradual increase in likelihood with each succeeding month until the following September.

The second team (Chen et al.) analyzed some 9.5 million children and adolescents in the same reserch database, and found that those born in August were 67% more likely to be diagnosed with ADHD than those born in September, after adjusting for age, sex, residence, and income. August births were also almost twice as likely (80% more likely) as September births to be on long-term treatment with ADHD medications.

The first team also performed a meta-analysis of eleven studies with a combined total of over 580,000 participants in North America (the U.S. and Canada), Europe (U.K., Germany, Norway, Sweden, Denmark), Asia (China, Taiwan, South Korea), and Oceania (Australia). Children born in the summer (June through August) were 13% more likely to be diagnosed with ADHD than the year-round mean, whereas those born in autumn were 13% less likely to be diagnosed with ADHD. This confirms that this pattern is not confined to Taiwan. It is worldwide.

Note carefully that the sharp discontinuity between August and September corresponds with the break-of point that decides which children get assigned to which school class. Anyone who turns a certain age by the start of the school year in September is included in the class associated with that age, whereas those turning the same age later are held back in the following class. That means that in any given class, those born in September are the oldest children and those born in August the youngest.

As signaled earlier, the likelihood of an ADHD diagnosis should be independent of something as obviously arbitrary as a birth month. That suggests there may be an unconscious bias trending against younger students when it comes to diagnosis.

Chen et al. concluded, "The effect of relative age on diagnoses and prescriptions was determined to last from childhood to adolescence but attenuated with age. Relative age is an indicator of brain maturity in cognition, behavior, and emotion and may thus play a critical role in the likelihood of being diagnosed as having childhood mental disorders and subsequently being prescribed psychotropic medication. Therefore, clinicians should consider the relative age effect in the childhood mental health care context."

September 14, 2023

Possible Connection: Maternal Thyroid Dysfunction and ADHD in Offspring

Is there an association between maternal thyroid dysfunction during pregnancy and ADHD in offspring?

Hyperthyroidism, an overactive thyroid gland, occurs in about one in five hundred women. It has been tied to adverse effects in both mother and fetus, including pre-eclampsia (a condition in pregnancy characterized by high blood pressure, sometimes with fluid retention and excessive protein in the urine, which can indicate kidney damage), preterm delivery, heart failure, and in uteri retardation of growth.

In hypothyroidism, on the other hand, thyroid activity is abnormally low, which retards growth and mental development. It is particularly common in regions with widespread iodine deficiency. Depending on the region, it affects one in three hundred to one in thirty women. Maternal hypothyroidism is associated with an increased risk of pre-eclampsia, premature separation of the placenta from the wall of the uterus, miscarriage, in uteri growth retardation, and fetal death.

The fetus relies on maternal thyroid hormones until its own thyroid function initiates halfway through pregnancy. As we have just seen, this direct link in the early stages of pregnancy has serious consequences described above. Does it also affect the risk of developing ADHD in offspring?

A team of researchers based in Hong Kong reformed a comprehensive search of the peer-reviewed medical literature on this subject. It then conducted two meta-analyses, one examining maternal hyperthyroidism during pregnancy, the other on maternal hypothyroidism.

The meta-analysis for maternal hyperthyroidism during pregnancy combined two nationwide cohort studies with a total of over 3.1 million persons, using the Danish and Norwegian medical registries. It found a slight but significant association with ADHD in offspring.

The meta-analysis for maternal hypothyroidism during pregnancy included the same two nationwide cohort studies, plus an Israeli nationwide cohort study (along with a tiny U.S. cohort study), with a total of over 3.4 million persons. It likewise found a slight but significant association with ADHD in offspring.

Though the component studies did some assessment of confounders, the authors of the meta-analyses noted, "By including a more comprehensive range of confounding factors and biologically relevant covariate (e.g. thyroxine treatment), future studies are warranted to re-visit the association between maternal thyroid dysfunction and various health outcomes in offspring."

December 8, 2023

Is There an Association Between Perfluoroalkyl Substances (PFAS)-exposure in Infancy and ADHD?

Is There an Association Between Perfluoroalkyl Substances (PFAS)-Exposure in Infancy and ADHD?

Although there are numerous kinds of perfluoroalkyl substances (PFAS), the primary ones used in the manufacture of fluoropolymers are perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Because of their strong water-repelling properties, fluoropolymers are used in stain repellents, polishes, paints, and other coatings, as well as in water-resistant outdoor clothing. They are long-lasting and therefore both pervasive in the home and environment and subject to accumulation in our bodies, especially in urbanized and industrialized areas. These substances can be passed from mother to child both through the placenta and through breastfeeding.

With support from the European Union, a large international team of European and North American researchers set out to investigate possible associations between early-life exposure to PFOS and PFOA and subsequent ADHD. They performed a meta-analysis on nine European population studies encompassing 4,826 mother-child pairs.

Participants were restricted to live-born single births with data on concentrations of PFOS and/or PFOA, and available information on ADHD diagnosis or symptoms.

Because a) some studies looked at maternal serum/plasma, others at maternal breast milk; b) timing of sample collection varied (first trimester, delivery); and c) children's levels during the first two years of life were unavailable (ethical constraints limit drawing blood samples from infants), the team used a validated pharmacokinetic model of pregnancy and lactation to estimate pre-and postnatal concentrations of PFASs in offspring.

The team adjusted for seven potential confounders: maternal pre-pregnancy body mass index, maternal age at delivery, maternal education, maternal smoking, number of previous children, duration of breastfeeding, and child sex.

With these adjustments, no association was found between estimated exposures to either PFOS or PFOA at birth, at three months, and at two years and subsequent diagnosis or symptoms of ADHD. While the raw data showed slightly higher odds for girls than for boys to develop ADHD with identical exposures, the differences were statistically non-significant.

November 27, 2023

Systematic review finds association between ADHD and gaming disorder

Systematic review finds association between ADHD and gaming disorder

The specific type of gaming disorder (GD) that is the focus of this review is "disordered video-gaming," or more precisely the addictive potential of interactive video games played on mobile phones, gaming consoles, individual computers, and over networks. Certain characteristics of such games, including structured rewards and multi-modal sensory stimulation, contribute to that addictive potential. Networked games also allow for direct social engagement through role playing and cooperation with others. They also lead to further opportunities for participation in a wider community of players on forums outside gameplay, such as discussion platforms, video play-through analyses, or live-streaming.

The authors performed a systematic search of the peer-review literature, and identified 29 studies exploring the relationship between Addend GD.

All studies found a positive association between ADHD and GD. Of studies reporting effect sizes, seven reported small effect sizes, three reported medium ones, and three reported large ones. There was a similarly wide variety of reported effect sizes among studies that reported correlations between ADHD scales and GD scales. These ranged from r = .12 (small) to r = .45(large).

Three studies examined longitudinal outcomes. One reported that lower ADHD scores at baseline predicted positive long-term recovery. Another noted that GD was more likely to develop into significant psychiatric symptoms and poorer educational outcomes two years later. The third study found that higher ADHD and GD scores were associated with higher incidences of delinquent or aggressive behaviors and externalizing problems, as compared to a sample with ADHD but not GD. All three studies reported that ADHD was a risk factor for the development of problematic gaming behavior. There was no clear indication of the reverse relationship - GD predicting ADHD.

The authors concluded, "This review found a consistent positive association between ADHD and GD, particularly for the inattention subscale. The strength of the association between ADHD and GD was variable. On symptom severity ratings, there was a positive relationship between scores measuring GD and ADHD pathology in some studies. Fewer studies in this review showed hyperactivity was commonly associated with GD. It is well known that hyperactivity in ADHD tends to improve significantly with age. It is possible that the natural progression of the disorder resulted in lower rates of hyperactivity. Such a hypothesis is strengthened by findings of a stronger association with hyperactivity among children aged between 4 and 8."

Ideas for policy interventions to address disordered video gaming include:

·        Parental controls on games.
·        Warning messages similar to those on cigarette packaging.
·        Organizing help services for gamers.

The authors called for further study on:

·        Effectiveness of intervention strategies.
·        The contribution of GD to the dysfunction associated with ADHD.
·        The relationship between the content of play (e.g., violence) and motivation to play (e.g., escapism) and ADHD symptoms.
role-playin·        The role of depression, anxiety, and another comorbidity in mediating the relationship between ADHD and GD

"Clinicians should beware that ADHD is common in GD," the authors emphasized, "and we, therefore, recommend that ADHD is screened for when evaluating GD as part of routine practice. This would ensure interventions aimed at ADHD can be successfully combined with GD treatment, potentially improving patient outcomes."

October 20, 2021

Meta-analysis Finds "Parent-Training" Helpful in Raising Children with ADHD

Meta-analysis finds behavioral parent training broadly helpful in raising children with ADHD

The aim of behavioral parent training is to improve the child's behavior through improved parenting. Noting that "it is unknown which of its components are most effective," a Dutch team of researchers conducted a systematic search of the peer-reviewed medical literature to identify randomized controlled trials (RCTs) suitable for meta-analysis.

Twenty-nine RCTs with a combined total of 2,345 participants met the criteria.

The team explored five types of outcome variables:

·        Positive parenting: behaviors such as reinforcement, monitoring, stimulating, and guiding the child.
·        Negative parenting: behaviors such as corporal punishment, harsh discipline, inconsistent parenting, and poor monitoring.
·        Parenting sense of competence: the extent to which parents perceive themselves as competent or effective in raising their child.
·        Quality of the parent-child relationship: signs of affection, support, sensitivity, and responsiveness.
and behavioral parent training aims:
·        Parental mental health: measures included parenting stress and several indices of parental psychopathologies, such as depression and anxiety.

A meta-analysis of 19 RCTs with 1,070 participants found a medium effect size improvement in positive parenting. Evidence of publication bias was borderline, but a trim-and-fill adjustment still reported a medium effect size reduction in ADHD symptoms. Similarly, limiting the meta-analysis to the 12 RCTs that were probably blinded made no difference in the outcome.

A second meta-analysis, of 15 RCTs with 878 participants, found a small-to-medium effect size reduction in negative parenting, after adjusting for publication bias. Limiting the meta-analysis to the six RCTs that were probably blinded modestly increased the effect size.

After adjusting for publication bias, a meta-analysis of 13RCTs with a combined total of 783 participants reported a small-to-medium effect size improvement in the quality of parent-child relationships. Limiting the meta-analysis to the six RCTs that were probably blinded made no difference in the outcome.

After adjusting for publication bias, a meta-analysis of 17 RCTs with a combined total of 1,083 participants reported a medium effect size improvement in parent sense of competency.

Finally, with no sign of publication bias, 23 RCTs with a combined total of 1,191 participants found a small-to-medium effect size improvement in parental mental health.

The team concluded, "Parent training had robust small- medium-sized positive effects on all parental outcomes relative to control conditions, both for unblinded and probably blinded measures. ... A reassuring finding was that effect sizes on positive parenting, negative parenting, and the parent-child relationship did not differ between probably blinded and unblinded measures, indicating that effects are not merely attributable to parents' investment affecting their assessment of outcome measures."

October 26, 2023

Children with ADHD have considerably greater odds of being victimized in reported sexual crimes

Children with ADHD have considerably greater odds of being victimized in reported sexual crimes

Youths with disabilities face varying degrees of social exclusion and mental, physical, and sexual violence.

A Danish researcher used the country's extensive national registers to explore reported sexual crimes against youths across the entire population. Of 679,683 youths born from 1984to 1994 and between the ages of seven and eighteen, 8,039 (1.2 percent) were victims of at least one reported sex crime.

The sexual offenses in question included rape, sexual assault, sexual exploitation, incest, and indecent exposure. Sexual assault encompassed both intercourse/penetration without consent or engaged in with a youth not old enough to consent (statutory rape).

The study examined numerous disabilities, including ADHD, which was the most common one. It also performed a regression analysis to tease out other covariants, such as parental violence, parental inpatient mental illness, parental suicidal behavior or alcohol abuse, parental long-term unemployment, family separation, and children in public care outside the family.

In the raw data, youths with ADHD were 3.7 times more likely to be a victim of sexual crimes than normally developing youths. That was roughly equal to the odds for youths with an autism spectrum disorder or mental retardation, but considerably higher than for blindness, stuttering, dyslexia, and epilepsy (all roughly twice as likely to be victims of such crimes), and even higher than for the loss of hearing, brain injury, or speech or physical disabilities.

Looking at covariate, family separation, having a teenage mother, or being in public care almost doubled the risk of being a victim of sexual crimes. Parental violence or parental substance abuse increased the risk by 40 percent, and parental unemployment for over 21 weeks increased the risk by 30 percent. Girls were nine times more likely to be victimized than boys. Living in a disadvantaged neighborhood made no difference, and living in immigrant neighborhoods actually reduced the odds of being victimized by about 30 percent.

After adjusting for other risk factors, youths with ADHD were still almost twice as likely to be victims of reported sex crimes than normally developing youths. All other youths with disabilities registered significantly lower levels of risk after adjusting for other risk factors: for those who were blind, 60 percent higher risk; for those with autism, hearing loss, or epilepsy, 40 percent higher risk. Communicative disabilities - speech disability, stuttering, and dyslexia - actually turned out to have protective effects.

This points to a need to be particularly vigilant for signs of sexual abuse among youths with ADHD.

September 28, 2023

Methylphenidate May Help Reduce Risk of Mortality in Youths with ADHD

Methylphenidate is associated with reduced risk of all-cause mortality in youths with ADHD in a nationwide population cohort study

Youths with ADHD are at higher risk of suicide, burn injuries, road injuries, and more generally all-cause mortality than normally developing children. Methylphenidate (MPH) is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of all-cause mortality? A team of Taiwanese researchers, collaborating with two British researchers, explored that question by looking at a nationwide population cohort.

Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using the National Health Insurance Research Database (NHIRD), the team identified over 183,000 youths under 18 with an ADHD diagnosis. Of these, just over 68,000 had been prescribed to MPH. The team matched them with an equal number of ADHD youths who were not prescribed MPH. All records were anonymized and checked against the National Mortality Register.

All-cause mortality was split into two subcategories. Unnatural-cause mortality consisted of homicide, suicide, and motor vehicle fatalities. Natural-cause mortality encompassed all other premature deaths. In the raw data, ADHD youths on MPH had half the all-cause mortality of those not on MPH. Natural-cause mortality was down about 40 percent and unnatural-cause mortality was by almost two-thirds. In the non-MPH group, 32 committed suicide in the follow-up year, versus only a single individual in the MPH group. There were seven homicide victims in the non-MPH group, versus none at all in the MPH group.

These staggering reductions, however, were almost exclusively among males. The team then adjusted for potential confounding variables - gender, age, residence, insurance premium, out-patient visits, and pre-existing diagnoses. In the adjusted model, the risk for all-cause mortality was still reduced - by about 20 percent - for those on MPH and remained statistically significant. Virtually identical reductions were found for males and for children first diagnosed with ADHD between 4 and 7 years old. But all other risk estimates became statistically non-significant, due in large measure to the rarity of mortality events.

The authors concluded, "This is the first study reporting that a longer interval between first ADHD diagnosis and first prescription of MPH is associated with a higher risk of all-cause mortality. In addition, we also found that participants receiving longer-duration MPH treatment had a lower risk of all-cause mortality. ... an implication is that receiving a diagnosis earlier and receiving medication earlier may reduce the risk of later adverse consequences."

They nevertheless cautioned, "although we adjusted for multiple covariant, information lacking in the database precluded the measurement of other possible confounders, such as family history, psychosocial stressors, the effect of behavioral therapy or severity of comorbidities. Therefore, as with all observational data, it is not possible to be conclusive about whether the association with lower mortality is related to an effect of MPH treatment itself or whether other characteristics of the children receiving MPH may account for the lower risk (i.e. confounding by indication).

Finally, although the cohort sizes were large, the number of deaths was small, and this limited statistical power, particularly for the investigation of cause-specific mortality and of subgroup differences. Because of the relatively low number of deaths and limited follow-up duration, longer-term studies with larger samples are warranted ..."

October 30, 2023

Methylphenidate May Reduce Risk of Burn Injury in Children with ADHD

Methylphenidate reduces risk of burn injury in children with ADHD in nationwide population cohort study

Children with ADHD are at higher risk of getting severe burns than normally-developing children. Burn injuries can be traumatic, imposing physical, psychological, and economic burdens on children, their families, and society. Methylphenidate is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of burn injuries?

A team of Taiwanese researchers collaborating with two British researchers explored that question by looking at a nationwide population cohort. Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using Taiwan's National Health Insurance Research Database(NHIRD), they identified over 90,000 youths under 18 years old with a diagnosis of ADHD. Youths who had burned injuries before diagnosis were excluded. ADHD youths were further divided into three groups: those not prescribed methylphenidate (over 22,000), those prescribed methylphenidate for less than 90 days (over 17,500), and those prescribed methylphenidates for 90 days or more(over 50,000).

Because methylphenidate is the only approved stimulant in Taiwan, it was the only stimulant analyzed in this study. Atomoxetine, a non-stimulant, is also approved in Taiwan, but only for those whose, outcomes with methylphenidate are suboptimal. It was only used by 4 percent of those on ADHD medication, and generally after prior use of methylphenidate, so there was no way to evaluate its effectiveness. Among ADHD youths not on methylphenidate, the proportion who got burn injuries was 6.7 percent. That dropped to 4.5 percent for those medicated for under 90 days, and to 2.9 percent for those on longer-term medication.

Calculations indicated that half of all burn injuries could have been prevented if all youths had been on methylphenidate. After adjusting for multiple confounders - seizure, intellectual disability, autism, conduct disorder, opposition defiant disorder, anxiety, depression, and psychotropic use (benzodiazepine, Z-drugs, antipsychotics, and antidepressants) that taking methylphenidate for any length of time was 38 percent less likely to suffer burn injuries. Moreover, longer-term medication had a greater beneficial effect. Those taking methylphenidate for under 90 days were 30 percent less likely to get burn injuries, whereas those taking it for 90 or more days were less than half as likely to get burn injuries as those not on methylphenidate.

The authors emphasized, "This nationwide population-based study has several strengths. First, the nationally representative sample was substantial and minimized selection bias. Second, patients with ADHD were identified through physician-based diagnoses. Third, all MPH [methylphenidate] prescriptions are recorded in the NHIRD, avoiding misclassification bias. Also, by excluding burn injuries before ADHD diagnosis, the reverse causal relationship between ADHD and burn injury was eliminated."

December 6, 2023

Sex Differences in ADHD Symptoms and Related Cognitive Deficits in Youths

Sex Differences in ADHD Symptoms and Related Cognitive Deficits in Youths

To what extent does sex matter in the expression of ADHD symptoms and associated cognitive deficits among youths with ADHD?

A recently published meta-analysis of 54 studies by a Canadian team of researchers at the University of Quebec at Montreal suggests it makes little to no difference. A meta-analysis of 26 studies with over 5,900 youths found no significant difference in inattention symptoms, and a meta-analysis of 24 studies with over 5,500 youths likewise found no difference in hyperactivity-impulsivity symptoms. Separating out hyperactivity and impulsivity made no difference.

Given these results, it's no surprise that a meta-analysis of 15 studies with over 3,500 youths again found no significant divergence between the sexes for total ADHD symptoms. Parents and teachers differed, however, in their ratings of symptoms. Whereas parents observed no differences, teachers reported boys had slightly more inattention and hyperactive-impulsive behaviors than girls. Turning to cognitive functions, a series of meta-analyses found no significant sex differences for interference control, working memory, and planning scores. But boys performed slightly worse on inhibition and motor response inhibition. While the raw data also showed boys slightly under-performing girls on cognitive flexibility, strong evidence of publication bias made this unreliable.

The team also compared youths with ADHD and youths without ADHD. Both for females and for males, those differences in ADHD symptoms were - as would be expected - extremely large, whether for total symptoms, inattention, or hyperactivity-impulsivity. All cognitive function scores were moderately better for normally developing boys compared with boys with ADHD, and for normally developing girls compared with girls with ADHD. Yet once again, when comparing these effect sizes between girls and boys, there were no significant differences for any of the symptom and cognitive function effects.

"In other words," the authors wrote, "boys and girls with ADHD presented significantly more primary symptoms and executive and attention deficits than did their peers without ADHD, and effect sizes were not significantly different between the sexes." They concluded, "girls with ADHD do not differ from boys with ADHD in many domains of cognitive functioning, and they have significantly more severe difficulties across the executive and attentional functions measured relative to girls without ADHD. This meta-analysis is the first to examine sex differences in cognitive flexibility, working memory, and planning."

December 11, 2023

Stigma: Public attitudes towards children and adults with ADHD

Stigma: Public attitudes towards children and adults with ADHD

To gauge the extent of stigma towards persons with ADHD, a European research team hired a company specialized in market and social research to conduct a poll of some five thousand randomly selected Germans. Just over a thousand completed the interview, representing a response rate of only one in five. The team acknowledged, “Although non-responder bias has to be considered to be important, ethical considerations prohibited the collection of any detailed information on non-respondents.” The sample had slightly more women and elderly persons, and a higher average level of educational attainment relative to the German population as a whole. Sampling weights were used to compensate for these discrepancies.

The poll relied on computer-assisted telephone interviews. Interviews began with prerecorded vignettes of either a 12-year-old child or 35-year-oldadult exhibiting core symptoms of ADHD (such as “careless mistakes in schoolwork,” “does not follow through on instructions,” “easily distracted by extraneous stimuli”, “loses things”, “leaves his place in the classroom or when sitting at the dining table”). Half of those interviewed were presented with child vignettes, and half with adult vignettes. The gender of the person described varied randomly.

On a scale of one to five, respondents were asked to indicate levels of agreement with two statements: 1. ‘‘Basically, we are all sometimes like this person. It’s just a question of how pronounced this state is.’’ 2. “All in all, the problems of Robert / Anne are abnormal.” For both child and adult vignettes, two out of three respondents agreed that “we are all sometimes like this person.” One in three respondents considered the problems depicted in the child vignettes as abnormal. That dropped to one in four in the adult vignettes.

Next, respondents were asked whether they ever had a problem like this, and whether someone among their family or close friends ever had to deal with such a problem. For both vignettes, one in four acknowledged having had a problem like this, and half said a close friend or family member had such a problem.

On the assumption that “negative emotional reactions are an important consequence of negative stereotypes, leading to separation, discrimination and status loss,” respondents were probed for their specific emotional reactions. “I feel annoyed,” “I react angrily,” and “provokes my incomprehension” were interpreted as indicating varying levels of anger.“Provokes fear” and “Makes me feel insecure” were seen as indicating fear. “I feel uncomfortable” was viewed as indicating somewhere between fear and anger. On the other hand, “I feel the need to help,” “I feel pity,” and “I feel sympathy” were interpreted as “pro-social” responses.

Pro-social reactions were by far the most common. Over two-thirds felt a need to help a child, and over half to help an adult, in such a situation. In both instances, almost half felt sympathy, and a half or more felt pity. On the other hand, a quarter of respondents in each case felt annoyed, and just under one in five felt uncomfortable. Almost one in seven reacted angrily to the child vignette, and almost one in six to the adult vignette. Fear was the least frequent emotional reaction.

In the case of adults, respondents were also asked about their willingness to accept the person described in the vignette in seven social situations:

·        Working together
·        As a neighbor
·        Marrying into the family
·        Introducing to a friend
·        Renting a room
·        Recommending for a job
old adult·        Taking care of chi

While three out of four respondents were willing to accept such persons as co-workers, only one in three would recommend them for a job. Two out of three would accept such persons as neighbors, and almost as many to marry into the family. Three out of five would very willingly introduce such persons to friends. Slightly over half would rent a room to them. But less than one in three would be willing to have such individuals take care of their own children.

Older respondents were more likely to see the problems as“abnormal” and to seek greater social distance. Women, and respondents with higher levels of education, were less likely to see the problems as abnormal and more likely to respond in pro-social ways.

Though showing most Germans to be accepting of persons with ADHD, these findings still indicate a significant degree of stigma, though less than for other psychiatric conditions such as depression, schizophrenia, or alcohol dependence.

August 27, 2021

Is Prenatal Exposure to Bisphenol A (BPA) Associated with Childhood ADHD?

Is prenatal exposure to bisphenol A (BPA) associated with childhood ADHD?

A team of U.S. endocrinologists recently published the results of a meta-analysis examining a possible association between bisphenol A(BPA) and childhood ADHD. BPA is used in a variety of consumer products, including plastic bottles for food and drink, epoxy resins used to line cans of food, dental sealants, and the thermal receipts issued by stores.
A review of the literature found 29 rodent studies, but only three with humans. The human studies were too different from each other to be suitable for meta-analysis. One found no association between prenatal exposure and ADHD. A second found prenatal BPA exposure to be associated with teacher-reported hyperactivity in 4-year-old boys, but not girls. The third found is to be associated with hyperactivity scores in 3-year-old girls.
As the authors note, "Often, there is little human data available, particularly in the environmental toxicology/health fields, due to the time and expense of conducting epidemiological studies and the ethical barriers for human-controlled trials that involve human exposure to potentially hazardous chemicals. Thus, it is important to have methods for using animal data to inform human health hazard conclusions; indeed, animal models are traditionally used to study human health."
Twelve of the mice and rat studies, with a total of 709 rodents, were suitable for meta-analysis.
Overall these pointed to a tiny SMD effect size of 0.09, but it was not significant, with the odds of such a result being obtained by chance being almost one in four (p = 0.237). But when results from the 356 males and353 females were looked at separately, a significant sex difference emerged. There was essentially no effect on female rodents, with an effect size of -0.07and a 95% confidence interval of -0.27 to 0.14, widely spanning the zero mark, rendering the result statistically non-significant. Among male rodents, however, there was a small but statistically significant effect size (0.24), with a 95%confidence interval from 0.04 to 0.45. The odds of obtaining this outcome by chance were only one in 50 (p = .02).
This result must be viewed with caution, as rodent physiology often differs substantially from that of humans. The authors, therefore, conclude, "early BPA exposure is associated with a presumed hazard of hyperactivity in humans. Our conclusion is based on 'moderate' levels of evidence for the human and 'high' levels of evidence for animal literature."

June 26, 2021

Screening, Diagnosing and Managing ADHD in Children with Epilepsy

Guidelines for screening, diagnosing, and managing ADHD in children with epilepsy

A working group of the International League Against Epilepsy(ILAE), consisting of twenty experts spanning the globe (U.S., U.K., France, Germany, Japan, India, South Africa, Kenya, Brazil), recently published "consensus paper" summarizing and evaluating what is currently known about comorbid epilepsy with ADHD, and best practices.

ADHD is two to five times more prevalent among children with epilepsy. The authors suggest that ADHD is underdiagnosed in children with epilepsy because its symptoms are often attributed either to epilepsy itself or to the effects of antiepileptic drugs (AEDs).

The working group did a systematic search of the English-language research literature. It then reached a consensus on practice recommendations, graded on the strength of the evidence.

Three recommendations were graded A, indicating they are well-established by evidence:
·        Children with epilepsy with comorbid intellectual and developmental disabilities are at increased risk of ADHD.
·        There is no increased risk of ADHD in boys with epilepsy compared to girls with epilepsy.
·        The anticonvulsant valproate can exacerbate attentional issues in children with childhood absence epilepsy (absence seizures look like staring spells during which the child is not aware or responsive). Moreover, a single high-quality population-based study indicates that valproate use during pregnancy is associated with inattentiveness and hyperactivity in offspring.

Four more were graded B, meaning they are probably useful/predictive:
·        Poor seizure control is associated with an increased risk of ADHD.
·        Data support the ability of the Strengths and difficulties questionnaire (SDQ) to predict ADHD diagnosis in children with epilepsy: "Borderline or abnormal SDQ total scores are highly correlated with the presence of a validated psychiatric diagnosis (93.6%), of which ADHD is the most common (31.7%)." The SDQ can therefore be useful as a screening tool.
·        Evidence supports the efficacy of methylphenidate in children with epilepsy and comorbid ADHD.
·        Methylphenidate is tolerated in children with epilepsy.

At the C level of being possibly useful, there is limited evidence that supports that atomoxetine is tolerated in children with ADHD and epilepsy and that the combined use of drugs for ADHD and epilepsy (polytherapy) is more likely to be associated with behavioral problems than monotherapy. In the latter instance, "Studies are needed to elucidate whether the polytherapy itself has resulted in the behavioral problems, or the combination of polytherapy and the underlying brain problem reflects difficult-to-control epilepsy, which, in turn, has resulted in the prescription of polytherapy."

All other recommendations were graded U (for Unproven), "Data inadequate or conflicting; treatment, test or predictor unproven." These included three where the evidence is ambiguous or insufficient:
·        Evidence is conflicted on the impact of early seizure onset on the development of ADHD in children with epilepsy.
·        Tolerability for amphetamine in children with epilepsy is not defined.
·        Limited evidence exists for the efficacy of atomoxetine and amphetamines in children with epilepsy and ADHD.

There were also nine U-graded recommendations based solely on expert opinion. Most notable among these:
·        Screening of children with epilepsy for ADHD beginning at age 6.
·        Reevaluation of attention function after any change in antiepileptic drug.
·        Screening should not be done within 48 hours following a seizure.
·        ADHD should be distinguished from childhood absence epilepsy based on history and an EEG with hyperventilation.
·        Multidisciplinary involvement in transition and adult ADHD clinics is essential as many patients experience challenges with housing, employment, relationships, and psychosocial wellbeing.

June 14, 2021

Everything You Need to Know About ADHD

Everything You Need to Know About ADHD

You've heard all sorts of misinformation about Attention-Deficit/Hyperactivity Disorder(ADHD), whether from friends, the internet, or uninformed press articles:

"ADHD is not real."

"Pharmaceutical companies invented ADHD to make money."

"I'm just a little ADD."

"Natural solutions are the best for ADHD treatment."

ADHD symptoms were first described in the late 1700s, primarily among hyperactive boys. It was described variously over 200 years as "fidgeting," "defects of moral control," "hyperkinetic reaction," "minimal brain damage" and eventually ADD (Attention Deficit Disorder) in the 1980s and ADHD today.

Because the natural tendency toward hyperactivity decreased with age, ADHD was originally thought to be a developmental disorder that disappeared in mid-to-late adolescence. When medicines were developed and used in ADHD treatment for young boys, physicians stopped prescribing them around mid-adolescence, because it was presumed the condition had been remediated. They were wrong. We know now that ADHD persists into adulthood for about two-thirds of ADHD youth.

ADHD was not widely recognized in girls until the mid-1990s when it became clear that girls with ADHD were less disruptive than boys with ADHD and were not being appropriately diagnosed. Girls with ADHD show less of the physical hyperactivity of boys, but suffer from "dreaminess," "lack of focus" and "lack of follow-through."

It was also in the 1990s that ADHD' pervasive comorbidity with depression, anxiety, mood, and autism spectrum disorders was established. At the same time, researchers were beginning to describe deficits in executive functioning and emotional dysregulation that became targets of substantial research in the 21st century.

Even with the 1990s recognition that ADHD is a lifetime disorder, equally present (in different forms) in both men and women, medical schools and continuing medical education courses (required for realizing sure of health professionals) have only begun to teach the most up-to-date evidence-based knowledge to the medical community. There still is much misinformation and a lack of knowledge among primary care professionals and the public.

ADHD Throughout the Lifespan
Most cases of ADHD start in Otero before the child is born. As a fetus, the future ADHD person carries versions of genes that increase the risk for the disorder. At the same time, they are exposed to toxic environments. These genetic and environmental risks change the developing brain, setting the foundation for the future emergence of ADHD.

In preschool, early signs of ADHD are seen in emotional lability, hyperactivity, disinhibited behavior and speech, and language and coordination problems. The full-blown ADHD syndrome typically occurs in early childhood, but can be delayed until adolescence. In some cases, the future ADHD person is temporarily protected from the emergence of ADHD due to factors such as high intelligence or especially supportive family and/or school environments. But, as the challenges of life increase, this social, emotional, and intellectual scaffolding is no longer sufficient to control the emergence of disabling ADHD symptoms.

Throughout childhood and adolescence, the emergence and persistence of the disorder are regulated by additional environmental risk factors such as family chaos, as well as the age-dependent expression of risk genes that exert different effects at different stages of development. During adolescence, most cases of ADHD persist and by the teenage years, many youths with ADHD have onset with a mood, anxiety, or substance use disorder. Indeed, parents and clinicians need to monitor ADHD youth for early signs of these disorders. Prompt treatment can prevent years of distress and disability.

By adulthood, the number of comorbid conditions increases, including obesity, which likely impacts future medical outcomes. Emerging data shows people with ADHD to be at increased risk for hypertension and diabetes. ADHD adults tend to be very inattentive but show fewer symptoms of hyperactivity and impulsivity. They remain at risk for substance abuse, low self-esteem, injuries due to accidents, occupational failure, and social disability, especially if they are not treated for the disorder.

Seven Important Concepts About ADHD


There are approximately 10 million U.S. adults with ADHD, 9 million of whom are undiagnosed. But with diligent research by the medical profession, we have learned seven important concepts about ADHD:
1.    ADHD has been documented worldwide in 5% of the population.
2.    Sixty-seven percent of ADHD children grow into ADHD adults and seniors. ADHD is heritable, runs in families, and is impacted by the physical environment and familial lifestyle.
3.    In youth, rates of ADHD are higher in males than females as males, but these rates even out by adulthood.
4.    ADHD coexists and is often masked by several other disorders: anxiety, depression, spectrum bipolar and autism disorder, substance abuse, alcoholism, obesity, risky behaviors, disorganized lives, working memory deficits, and significant executive dysfunctions that affect personal, social, and work success.
5.    ADHD medications(stimulants and non-stimulants) are the most effective treatments for ADHD symptoms. Psychological support/training designed for ADHD, and lifestyle modifications, are important adjuncts to medicine.
6.    ADHD costs the U.S. economy more than $100 million annually in lost productivity, accidents, hospitalizations with comorbidities, and family and professional support for ADHD patients.
7.    ADHD is diagnosable and safely treatable in trained primary care practices.

How do you know if you or someone you love has ADHD? Evaluate your life against the seven concepts above. Then get screened and diagnosed by a health care professional. The diagnosis of ADHD should be done only by a licensed clinician who has been trained in ADHD. That clinician should have one goal in mind: to plan a safe and effective course of evidence-based treatment.

When diagnosing adults, it is also useful to collect information from a significant other, which can be a parent for young adults or a spouse for older adults. But when such individuals are not available, diagnosing ADHD based on the patient's self-report is valid. Just remember that personal, work, and family lives are improved with treatment. Research and technology related to ADHD improve all the time.

ADHD in Adults is a great resource for anyone interested in learning more about ADHD, with evidence-based information and education for both healthcare professionals and the public. The website also features a new ADHD screener for predicting the presence of ADHD in adults.

Stephen V. Faraone, Ph.D., is a Distinguished Professor of Psychiatry and Neuroscience & Physiology at SUNY Update Medical University and a global expert on Adult ADHD.

March 12, 2021

Stigma: Public attitudes towards children and adults with ADHD

Stigma: Public attitudes towards children and adults with ADHD

To gauge the extent of stigma towards persons with ADHD, a European research team hired a company specialized in market and social research to conduct a poll of some five thousand randomly selected Germans. Just over a thousand completed the interview, representing a response rate of only one in five. The team acknowledged, "Although non-responder bias has to be considered to be important, ethical considerations prohibited the collection of any detailed information on non-respondents." The sample had slightly more women and elderly persons, and a higher average level of educational attainment relative to the German population as a whole. Sampling weights we reused to compensate for these discrepancies.

The poll relied on computer-assisted telephone interviews. Interviews began with prerecorded vignettes of either an a12-year-old child or a 35-year-old adult exhibiting core symptoms of ADHD (such as "careless mistakes in schoolwork," "does not follow through on instructions," easily distracted by extraneous stimuli, "loses things", "leaves his place in the classroom or when sitting at the dining table"). Half of those interviewed were presented with child vignettes and half with adult vignettes. The gender of the person described varied randomly.

On a scale of one to five, respondents were asked to indicate levels of agreement with two statements: 1. "Basically, we are all sometimes like this person. It's just a question of how pronounced this state is." 2. "All in all, the problems of Robert / Anne are abnormal." For both child and adult vignettes, two out of three respondents agreed that "we are all sometimes like this person." One in three respondents considered the problems depicted in the child vignettes as abnormal. That dropped to one in four in the adult vignettes.

Next, respondents were asked whether they ever had a problem like this and whether someone among their family or close friends ever had to deal with such a problem. For both vignettes, one in four acknowledged having had a problem like this, and half said a close friend or family member had such a problem.

On the assumption that "negative emotional reactions are an important consequence of negative stereotypes, leading to separation, discrimination and status loss," respondents were probed for their specific emotional reactions. "I feel annoyed," " react angrily," and" provokes my incomprehension" were interpreted as indicating varying levels of anger. "Provokes fear" and "Makes me feel insecure" were seen as indicating fear. "I feel uncomfortable" was viewed as indicating somewhere between fear and anger. On the other hand, "I feel the need to help," "I feel pity," and "I feel sympathy" were interpreted as "pro-social" responses.

Pro-social reactions were by far the most common. Over two-thirds felt a need to help a child, and over half to help an adult, in such a situation. In both instances, almost half felt sympathy, and a half or more felt pity. On the other hand, a quarter of respondents in each case felt annoyed, and just under one in five felt uncomfortable. Almost one in seven reacted angrily to the child vignette, and almost one in six to the adult vignette. Fear was the least frequent emotional reaction.

In the case of adults, respondents were also asked about their willingness to accept the person described in the vignette in seven social situations:

·      Working together
·      As a neighbor
·      Marrying into the family
·      Introducing to a friend
·      Renting a room
·      Recommending for a job
·      Taking care of children

While three out of four respondents were willing to accept such persons as co-workers, only one in three would recommend them for a job. Two out of three would accept such persons as neighbors, and almost as many to marry into the family. Three out of five would very willingly introduce such persons to friends. Slightly over half would rent a room to them. But less than one in three would be willing to have such individuals take care of their children.

Older respondents were more likely to see the problems as "abnormal" and to seek greater social distance. Women, and respondents with higher levels of education, were less likely to see the problems as abnormal and more likely to respond in pro-social ways.

Though showing most Germans to be accepting of persons with ADHD, these findings still indicate a significant degree of stigma, though less than for other psychiatric conditions such as depression, schizophrenia, or alcohol dependence.

March 10, 2021

Taiwanese Population Study Finds Strong Association Between Cleft Lip and Palate and Subsequent ADHD

Congenital cleft lip and palate (CCLP) are birth defects associated with genetic and environmental factors. The latter include heavy maternal consumption of alcohol and fetal exposure to retinoid drugs derived from vitamin A. 

Methods:

Taiwan has an island-wide single-payer health insurance system that reaches over 99% of the population. To explore the relationship between CCLP and various psychiatric disorders including ADHD, a Taiwanese study team used the island’s National Health Insurance Research Database to identify all 1,158 children and adolescents with CCLP during a ten-year period. They matched them ten-to-one with 11,580 age and sex-paired controls without CCLP. 

Summary of Results:

Further adjusting for demographic data (income, residence) and family history of major psychiatric disorders, children and adolescents with CCLP were more than seven times more likely to be diagnosed with ADHD during the follow-up period than controls. Patients with both cleft palate and cleft lip were more than nine times more likely to be subsequently diagnosed with ADHD than controls. 

Patients with CCLP were also six times more likely to be diagnosed with autism spectrum disorder and more than seven times as likely to be diagnosed with schizophrenia as non-CCLP controls. They were also more likely to be diagnosed with bipolar disorder or major depressive disorder, but these results did not reach statistical significance. 

Conclusion:

This study highlights a significant association between congenital cleft lip and palate (CCLP) and an increased risk of developing ADHD, with CCLP patients being more than seven times as likely to be diagnosed with the disorder. Additionally, CCLP was linked to a higher prevalence of other psychiatric conditions, including autism spectrum disorder and schizophrenia. These findings underscore the importance of monitoring mental health in individuals with CCLP and call for further research into the risk factors connecting these birth defects with psychiatric disorders.

 

December 9, 2024