July 26, 2024

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.

Hely Bassalov, Noa Yakirevich-Amir, Inbal Reuveni, Catherine Monk, Sharon Florentin, Omer Bonne, and Ilan Matok, “Prenatal Cannabis Exposure and The Risk for Neuropsychiatric Anomalies in the Offspring: A Systematic Review and Meta-Analysis,” American Journal of Obstetrics and Gynecology (2024), https://doi.org/10.1016/j.ajog.2024.06.014.

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Swedish Nationwide Population Study Finds Strong Association Between ADHD and Sleep Disorder Diagnoses and Sleep Medication Prescriptions

There has been consistent evidence of an association between ADHD and subjectively reported sleep problems even in patients not medicated for the disorder. There have also been studies using wrist-worn actigraphy (a wrist watch-like device that measures gross motor activity) and sleep lab-based polysomnography that measure objective sleep parameters. 

What has been missing are large population-based cohort studies to explore the prevalence rates of different sleep disorders and medical prescriptions in ADHD. 

Methods Used: 

Sweden has a single-payer health insurance system and a series of national population registers that track virtually its entire population. Using the Swedish Total Population Register, a local research team created a cohort of all 6,470,658 persons born between 1945 and 2008. They linked this to the Swedish National Patient Register, which includes inpatient hospitalizations from 1975 to 2013, and outpatient specialist diagnoses from 2001 to 2013, to identify diagnoses of sleep disorders. They also linked to the Prescribed Drug Register, covering 2005 to 2013, to identify prescriptions for sleep medications. 

Summary of Findings: 

Overall, persons with ADHD were eight times more likely to be diagnosed with any sleep disorder relative to normally developing peers. Broken down by age, adolescents with ADHD were 16 times more likely to receive such diagnoses, young adults (18-30) twelve times more likely, children and mid-age adults (31-45) eight times more likely, and older adults six times more likely. 

Broken down by specific sleep disorder diagnoses, relative to normally developing peers, persons with ADHD were: 

  • Five times more likely to have sleep terrors and seven times more likely to have nightmares. 
  • Six times more likely to sleepwalk. 
  • Seven times more likely to have restless leg syndrome. 
  • Sixteen times more likely to have insomnia. 
  • Nineteen times more likely to have disorders of sleep/wake schedule (circadian rhythms). 
  • Twenty times more likely to have hypersomnia (excessive sleeping). 
  • Over seventy times more likely to exhibit narcolepsy (daytime sleepiness) and cataplexy (sudden loss of muscle tone leading to collapse). 

As for sleep medication, relative to normally developing peers, persons with ADHD were: 

  • Seven times more likely to be prescribed the hypnotic zolpidem (Ambien). 
  • Eight times more likely to be prescribed the hypnotic zopiclone or the antihistamine propriomazine. 
  • Ten times more likely to be prescribed the sedative and hypnotic zaleplon (Sonata). 
  • Fourteen times more likely to be prescribed any sleep medication. 
  • 37 times more likely to be prescribed melatonin, the body’s natural sleep-inducing hormone, which is a prescription medication in Europe. 

Conclusion: 

The team concluded, “Our findings also suggest that greater clinical attention should be directed towards addressing sleep problems in individuals with ADHD. This entails implementing proactive measures through sleep education programmes and providing both pharmacological and non-pharmacological approaches such as cognitive behavioural therapy and parental sleep training.” 

December 12, 2024

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