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.” 

Rebecca Kristine Kappel, Tania Hviid Bisgaard, Gry Poulsen, and Tine Jess, “Risk of Anxiety, Depression, and Attention-Deficit/ Hyperactivity Disorder in Pediatric Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study,” Clinical and Translational Gastroenterology (2024), 15:e00657, https://doi.org/10.14309/ctg.0000000000000657

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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

ADHD from Childhood to Adulthood

ADHD from Childhood to Adulthood

Although ADHD was conceived as a childhood disorder, we now know that many cases persist into adulthood. My colleagues and I charted the progression of ADHD through childhood, adolescence, and adulthood in our "Primer" about ADHD,http://rdcu.be/gYyV.  Although the lifetime course of ADHD varies among adults with the disorder, there are many consistent themes, which we described in the accompanying infographic.  Most cases of ADHD startin uterobefore 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, 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 along with 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 has increased, including obesity, which likely has effects on future medical outcomes.

The ADHD adult tends to be very inattentive by showing fewer symptoms of hyperactivity and impulsivity. They remain at risk for substance abuse, low self-esteem, occupational failure, and social disability, especially if they are not treated for the disorder.  Fortunately, there are several classes of medications available to treat ADHD that are safe and effective. And the effects of these medications are enhanced by cognitive behavior therapy, as I've written about in prior blogs.

March 30, 2021

Children with ADHD At Greater Risk 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

Transcranial Direct Current Stimulation for ADHD Symptoms and Executive Function

Meta-analysis finds benefits of transcranial direct current stimulation for ADHD symptoms and executive function—but evidence remains weak

Background

A meta-analysis examined whether noninvasive brain stimulation (NIBS) techniques could help reduce core symptoms of ADHD and improve cognitive function. NIBS refers to techniques that stimulate brain activity using low electrical or magnetic currents applied from outside the head. They studied transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), while newer methods like tRNS (random noise) and tACS (alternating current) lacked enough studies to be included in the analysis.

Methods

Only randomized controlled trials (RCTs)—considered the gold standard in clinical research—were included in the review. For tDCS, the results were promising:

-A meta-analysis of 12 studies (582 participants) showed small but statistically significant improvements in inhibitory control (the ability to stop or delay responses).

-Nine studies (390 participants) showed small-to-medium improvements in working memory.

-Two smaller studies (94 participants) hinted at improvement in cognitive flexibility, but the results were not strong enough to be considered reliable.

-Seven studies (277 participants) found medium-to-large improvements in linattention, though results varied significantly between studies.

 Hyperactivity and impulsivity showed some improvement, but again, the number of studies was too small to draw firm conclusions.

 For rTMS, however, the results were not as encouraging. A meta-analysis of three studies (137 participants) found no significant improvement in ADHD symptoms.

Conclusion

While the results suggest that tDCS may offer some benefit for executive functions and attention in people with ADHD—especially when targeting specific brain areas like the F3/F4 regions (roughly over the dorsolateral prefrontal cortex)—the authors emphasize the need for further research. Most studies didn’t include long-term follow-up, and there’s still a lack of consistency in how stimulation is applied across studies.  Moreover, even when positive findings emerged for executive functions is not clear how these translate into changes that are meaningful for the patient.

Importantly, this study doesn’t suggest that NIBS should replace standard treatments. Although the paper highlights challenges with medication adherence and side effects, ADHD medications and behavior therapies remain the most well-established and effective treatments for most patients. The improvements seen with NIBS so far are relatively small and preliminary in comparison.

Instead, the findings support the idea that NIBS could one day serve as a complementary tool—especially for individuals who don’t respond well to existing treatments. But until more rigorous and long-term studies are done, NIBS should be viewed as an experimental approach, not a substitute.

 

 

 

May 22, 2025

Seven New Meta-analyses Suggest Wide Range of Benefits from Exercise for Persons with ADHD

Seven New Meta-analyses Suggest Wide Range of Benefits from Exercise for Persons with ADHD

ADHD is associated with deficits in executive functions. These are mental processes that enable individuals to plan, focus attention, manage tasks, and regulate emotions. These skills encompass working memory, cognitive flexibility, and inhibitory control, which are crucial for goal-directed behavior and decision-making. 

Working memory, which temporarily stores and processes information, contributes to language development by helping individuals make sense of what they read or hear.  

Cognitive flexibility refers to the ability to change perspectives, adapt thinking strategies, adjust to changing needs and priorities, recognize errors, and grasp opportunities.  

Inhibition switching involves intentional control of attention and emotions, suppressing automatic responses when necessary to prevent inappropriate behavior.  

These elements are critical to academic, social, and professional success. 

An international study team (Li et al.) conducted a meta-analysis of randomized controlled trials (RCTs) to explore the efficacy of physical activity for improving executive functions among children with ADHD aged 6 to 12. 

Meta-analysis of eleven RCTs encompassing 388 children reported a medium-to-large effect size improvement in cognitive flexibility. However, it found no benefit from aerobic exercise (such as running, jumping). When limited to the nine studies with 301 children that focused on cognitively engaging exercise (such as soccer and water sports that require constant monitoring of other players and strategizing), it found a large effect size improvement. Correcting for possible publication bias had no effect on the outcome. 

Meta-analysis of nine RCTs totaling 398 children reported a large effect size improvement in working memory. Once again, it found no benefit from aerobic exercise. Focusing on the seven RCTs with 288 children that used cognitively engaging exercise, it found a very large effect size improvement. There was no sign of publication bias. 

Meta-analysis of fourteen RCTs combining 579 children reported a small-to-medium effect size improvement in inhibition switching. But whereas it found a medium effect size improvement for shorter interventions of less than an hour (eight RCTs, 334 children), it found no benefit from interventions lasting an hour or more (six RCTs, 245 children. Again, there was no sign of publication bias. 

The team concluded, “Our study shows that physical activity interventions have a positive effect on improving executive function in school-age children with ADHD, with cognitive-engaging exercises showing greater benefits across three executive function measures.” 

A Chinese study team (Yang et al.) performed a related meta-analysis on the effect of exercise on inhibitory control in adults. Combining eight RCTs with a total of 372 participants, it reported a very large effect size improvement in inhibitory control, primarily from regular exercise. However, the effects were heavily influenced by a couple of outliers. The team claimed to have performed a sensitivity analysis but offered no evidence. Likewise, they noted signs of publication bias but did not use the standard trim-and-fill analysis to correct for it. 

Another Chinese study team (Xiangqin Song et al.) examined the effect of exercise on working memory in children and adolescents.  

Meta-analysis of 17 RCTs encompassing 419 participants found a medium effect size improvement in working memory. The large effect size improvement for cognitive aerobic exercise (4 RCTs, 233 participants) was twice the effect size for simple aerobic exercise (8 RCTs, 397 participants), though this meta-analysis still found a small-to-medium effect size gain from the latter. There was no sign of publication bias.  

The team concluded, “The results indicate that cognitive-aerobic exercise and ball sports are significantly more effective than other types of exercise interventions in improving working memory. This difference may be attributed to the varying cognitive load, task complexity, and the degree of activation of executive functions across different exercise types. The findings suggest that when designing exercise interventions for children with ADHD, priority should be given to exercise types with higher cognitive load in order to more effectively enhance working memory.” 

A joint Australian-U.S. team (Singh et al.) conducted a meta-meta-analysis on the effect of exercise on executive functions, that is, a meta-analysis of previous meta-analyses of RCTs.  

Combining ten separate meta-analyses with well over 2,800 children and adolescents with ADHD, it reported large effect size improvements in executive functions overall. There was no further breakdown by type of executive function and type of physical activity.  

The team concluded, “While exercise was seen to have a moderate and similar positive impact across all populations with respect to general cognition and memory, benefits for executive function were particularly marked in individuals with ADHD. This subgroup was unique in demonstrating a large effect size. This could be attributed to the task selection and the fact that many ADHD studies involved children. While the exact reason for this finding is unclear, there is evidence to suggest that impairments in executive function are common among individuals with ADHD. As such, it is plausible that this population may have a greater capacity for improvement due to starting from a lower baseline, compared with those with ‘normal’ executive function.” 

Another Chinese study team (Yagang Song et al.) performed a meta-analysis of RCTs examining the effects of physical exercise on anxiety, depression, and emotion regulation among children and adolescents with ADHD.  

Meta-analysis of eleven studies with a combined total of 384 participants reported a medium effect size reduction in symptoms of anxiety, with a dose-effect response. Physical exercise once a week had no significant effect, while twice a week was associated with a medium effect size reduction, and three or more times a week with a very large effect size improvement. Moderate intensity exercise was three times more effective than low intensity exercise.  

Meta-analysis of seven studies encompassing 187 individuals similarly reported a medium effect size reduction in symptoms of depression. Once again, moderate intensity was far more effective than low intensity exercise. 

Meta-analysis of seven studies totaling 429 children and adolescents reported a very large effect size improvement in emotion regulation, especially for physical exercise conducted at least twice a week

There was no sign of publication bias in the anxiety, depression, or emotion regulation findings. 

The team concluded, “Physical exercise demonstrated a substantial overall impact on enhancing anxiety, depression, and emotional regulation in children with ADHD, exhibiting a dose-response effect correlated with the period, frequency, duration, and intensity of the exercise. This investigation ... presents an additional evidence-based therapeutic approach for the considerable number of children with ADHD who are not appropriate candidates for pharmacological intervention.” 

A joint U.S.-Hong Kong study team (Liu et al.) performed a meta-analysis exploring the effect of physical exercise on motor proficiency. Motor proficiency includes both gross motor skills (like walking and running) and fine motor skills (like writing and buttoning).  

Meta-analysis of ten studies encompassing 413 children and adolescents with ADHD reported a very large effect size improvement in motor proficiency from physical exercise. The gains for object control, fine manual control, and manual coordination were roughly twice the gains for body coordination. There was no sign of publication bias. 

Finally, a Spanish research team (González-Devesa et al.) conducted a meta-analysis examining the effect of exercise on objectively measured sleep status among persons with ADHD. 

Meta-analysis of three RCTs with a combined total of 131 individuals that used accelerometers to measure sleep duration reported no significant effect one way or the other from exercise

The team concluded, “The existing evidence regarding the use of exercise to manage sleep problems in individuals with ADHD remains inconclusive. Preliminary findings from this review suggest a potential positive effect of exercise on self-reported sleep quality; however, its efficacy in improving sleep duration could not be confirmed.” 

The Take-Away:

An ideal exercise regimen for children with ADHD should focus on cognitively engaging physical activities rather than simple aerobic exercise. Sports and activities that require strategic thinking, attention to others’ actions, and rapid decision-making—such as soccer, martial arts, or water-based team sports—gave the best results, especially for working memory and cognitive flexibility. These types of exercise also show strong benefits for emotional regulation, reducing anxiety and depression, and enhancing motor proficiency.

To maximize benefits, the regimen should include moderate-intensity sessions at least two to three times per week, each lasting less than an hour, as longer durations appear less effective for improving inhibitory control. This structured, cognitively demanding approach offers an evidence-based, non-pharmacologic treatment option for children with ADHD, particularly for those who cannot or prefer not to use medication.  We need, however, more work to determine if exercise will provide the same symptom reduction and protection from adverse outcomes as has been shown for medications.

May 16, 2025

How Early Parent–Child Interactions May Shape the Expression of ADHD Traits: A Longitudinal Study

We know that Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with strong biological and genetic underpinnings; However, emerging research suggests that early environmental influences—particularly parent–child interactions—may shape how ADHD traits, such as impulsivity and delay aversion, are expressed during development.

This longitudinal study explored whether negative parental reactions during moments of delay contribute to the intensification of ADHD-related behaviors in preschool-aged children. A total of 112 mother–child pairs from the UK and Hong Kong participated. Children were screened for ADHD traits using the Strengths and Difficulties Questionnaire, ensuring a range of symptom severity. 

The experimental task—the Parent–Child Delay Frustration Task (PC-DeFT)—was designed to assess how children responded to brief, unpredictable waiting periods during a game-like activity, and how parents reacted in turn. During the task, children operated a button to change a red light to green, allowing their parent to retrieve a toy item. While most trials had no delay, six included unexpected 5–10 second pauses, creating mild frustration. Trained observers recorded children’s behavioral responses and parents' emotional reactions.

At follow-up (12–18 months later), teacher ratings revealed that children whose parents showed more negative reactions during delay trials (e.g., impatience, criticism) were more likely to exhibit increases in ADHD traits—especially impulsivity and difficulty waiting. Importantly, this link was mediated by increases in delay aversion, a motivational style where the child seeks to avoid frustrating waiting experiences. No such associations were found in free play or non-delay tasks, underscoring the specificity of this interaction.

The study’s findings suggest that, while these interactions do not cause ADHD, early social environments can influence how and when symptoms manifest. Interventions aimed at supporting positive parent–child interactions—particularly in challenging contexts like waiting—may help shape the developmental trajectory of children predisposed to ADHD.

May 15, 2025