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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.
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:
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.”
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.
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.
Methylphenidate is an effective treatment for ADHD in adults who also have bipolar disorder (BD), but it carries a potential risk of triggering manic episodes. Current guidelines therefore recommend using it only alongside mood-stabilizing medication. A new study using French nationwide claims data sought to test and extend those recommendations with greater statistical power than previous research.
The study built on findings by Viktorin et al. (2017), who observed that adults with BD not taking mood stabilizers had more than a sixfold higher risk of manic events (defined as hospitalization for mania or a new antimanic prescription) within six months of starting methylphenidate. Patients on mood-stabilizing treatment, by contrast, showed nearly half the baseline risk in the first three months. Those findings were limited, however, by small event counts (fewer than 61 manic episodes) and an effect that did not persist beyond the initial three-month window.
To build on this, researchers drew on the French National Health Data System (which is a claims database covering more than 60 million people) spanning 2008 to 2024. The final sample included 6,022 adults with BD (56% women) who had started methylphenidate. Using a self-controlled design, the study compared each patient's rate of manic events in the six months before their first methylphenidate prescription with the rate in the six months after, effectively eliminating stable individual differences as a confound.
Patients were classified as receiving continuous mood-stabilizing treatment if they had been dispensed at least two courses of specific antipsychotics (aripiprazole, olanzapine, or quetiapine) or mood stabilizers (lithium or valproate) in the nine months before starting methylphenidate, including at least one dispensation in the final six months of that window.
The results largely confirmed the earlier findings. Among the 2,745 patients not on mood stabilizers, the rate of inpatient mania diagnosis was 5.1 times higher in the first three months after starting methylphenidate, though this elevation fell to a non-significant level over the subsequent three months. Patients receiving continuous mood-stabilizing treatment showed no statistically significant change in mania risk across the full six-month post-initiation period. A formulation-specific pattern also emerged: patients without mood-stabilizing treatment had a 2.5-fold higher risk associated with extended-release methylphenidate, while no significant risk increase was seen with the immediate-release formulation or in treated patients regardless of formulation.
The authors conclude that methylphenidate at doses below 30 mg does not appear to elevate manic relapse risk when prescribed alongside mood stabilizers. The elevated risk seen in untreated patients, particularly with extended-release formulations, must be interpreted cautiously, given limited statistical power and the likelihood that it partly reflects the natural fluctuation of manic relapse over time. The authors flag this as an inherent limitation of self-controlled survival analyses when studying drug-induced mania, where temporal trends in the underlying condition can be difficult to disentangle from treatment effects.
The FDA has approved a new once-daily pill called centanafadine (trade name SIMTRIYO®). Approved for adults and kids aged 6 and older (weighing at least 44 lbs / 20 kg), centanafadine is a new category of ADHD treatment that aims to give fast results with fewer of the downsides of traditional stimulants.
To understand why centanafadine is unique among medications for ADHD, it helps to look at how ADHD brain chemistry works:
Stimulants like Ritalin and Adderall work mainly in the dopamine system. Nonstimulants like atomoxetine, viloxazine, clonidine and guanfacine work mainly on the norepinephrine system. Centanafadine is the first drug in a new class called NDSRIs (Norepinephrine, Dopamine, and Serotonin Reuptake Inhibitors). We can describe its effects as follows:
What Did Clinical Trials Show?
The FDA approved centanafadine based on studies involving thousands of adults, teens, and children. Here are the key findings:
Centanafadine showed some improvement in ADHD symptoms within the very first week of taking it although a full effect takes about six weeks.
In adult trials, taking 200 mg or 400 mg daily led to significant improvements in real-world skills:
In trials with children (ages 6–12) and teens (ages 13–17), centanafadine significantly reduced core ADHD symptoms like hyperactivity, impulsivity, and lack of focus compared to a placebo.
About 30% to 40% of adults with ADHD also suffer from anxiety. Traditional stimulants can make anxiety worse. In a trial specifically designed for adults dealing with both ADHD and anxiety, centanafadine effectively treated ADHD symptoms without firing up their anxiety, which might be due to its serotonin boost.
Does Centanafadine have Side Effects?
While Centanafadine was well-tolerated by most people in studies, like any prescription medication, it comes with important safety guidelines.
Prescribing Warnings:
Common Side Effects:
Other Warnings:
The Bottom Line
Overall, centanafadine is a new step forward in how we treat ADHD. Because it acts differently in the brain than traditional treatments, patients who struggle with stimulant-related anxiety or side effects may find it useful to explore with their doctor.
A landmark nationwide study from South Korea has uncovered a significant link between prenatal exposure to air pollution — specifically nitrogen dioxide (NO2) — and an increased risk of ADHD in children.
While researchers have long suspected that air pollutants interfere with fetal brain development through inflammation and oxidative stress, this study is one of the largest and most comprehensive of its kind, following nearly 1.5 million births for up to 13 years.
Why South Korea?
South Korea provided a unique countrywide “laboratory” for this research due to two key infrastructure strengths:
Key Findings: The “Smoking Gun” of NO2
While the study looked at several pollutants, nitrogen dioxide — a byproduct of fossil fuel combustion in cars and power plants — emerged as the primary concern.
Pollutant
Association with ADHD Risk
Nitrogen Dioxide (NO2)
Strongest Link: Every 1-ppb (part-per-billion) increase in exposure linked to a 22% rise in risk.
Sulfur Dioxide (SO2)
Minimal Link: Only a slight 4% increase per ppb.
Ozone (O3) carbon monoxide (CO), & particulates
No significant association was found.
The scale of the NO2 risk is particularly striking. Over the typical range of exposure levels found in the study (an interquartile range of 13 ppb), the data suggest a threefold increase in ADHD risk for children in the highest-exposure groups compared to the lowest.
Accounting for Other Factors
To ensure the results weren’t skewed by other variables, the researchers controlled for a wide range of confounders including:
The authors emphasized the strong association between maternal nitrogen dioxide exposure and ADHD, while also noting the small but significant association with sulfur dioxide.
The Take-Away: A New Frontier for Public Health
Historically, air quality laws have been designed to protect our lungs and hearts. However, this study adds to a growing body of evidence suggesting that the brain is likewise vulnerable.
In a commentary on the findings, expert George Ayoub argued that “neurodevelopment should be explicitly considered” when governments perform cost-benefit analyses on air quality regulation. My view is a bit different. The association is intriguing but the study does not establish cause and effect. Many statistically significant environmental risk associations for neurodevelopmental disorders have disappeared after controlling for maternal risk for ADHD. I hope this research team will do those analyses if feasible.
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