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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.
Vitamins play important roles in metabolism, immune regulation, and neurodevelopment. Recent studies show that deficiencies in vitamins like D, B6, B12, and folate are common in people with ADHD and ASD (autism spectrum disorder), and are associated with behavioral, cognitive, and brain development issues.
The Study:
A study team based in China has just performed a systematic search of the peer-reviewed medical literature to perform meta-analyses of clinical trials exploring vitamin interventions in the treatment of ADHD and ASD.
ADHD trials included participants with an official diagnosis. The primary intervention was vitamin supplements, while other treatments, including medications, remained unchanged or were excluded during the study period. ADHD outcomes included measurable changes in ADHD symptoms using validated rating scales and executive function measures.
Eligible studies included standard or sham control groups, crossover, parallel, or other clinical trial designs. In crossover studies, only first-phase data were analyzed to prevent carryover effects.
Ten trials with 852 participants met the standards, but meta-analysis showed no significant results. The outcomes varied widely, suggesting a need to distinguish among vitamins.
Results:
Of the five trials involving 347 participants that specifically evaluated vitamin D supplementation, results indicated a large effect size improvement in ADHD symptoms and executive function measures. The other five studies did not show any observable improvement.
Key limitations include:
The team concluded, “This meta-analysis supports the use of vitamin supplementation as a promising adjunctive treatment for ASD and ADHD. Vitamin B showed greater benefits in improving symptoms of ASD, while vitamin D was more effective in managing ADHD-related behaviors. These findings suggest that specific vitamins may target disorder-specific symptoms. Despite limitations such as the lack of trials on other vitamins and limited understanding of underlying mechanisms, vitamin therapy remains a low-cost, accessible option.”
An important limitation of this work is that the positive results for vitamin D were due to two studies from Iran. So far, no positive study has emerged from a non-Iranian study.
Interpretation:
The vitamin D findings are intriguing and could be important if replicated outside of Iran. Since supplementation is already widely recommended to those with limited sunlight exposure, clinicians may want to consider monitoring their patients’ vitamin D intake, especially in the winter months. It should be noted, however, that due to the limitations of this study, the results are by no means conclusive, and vitamin D should not be taken as a stand-alone treatment for ADHD.
Claims-based real-world data can reveal population-level trends in health among people with neurodevelopmental disorders. This new study examined the prevalence, demographics, and chronic comorbidities of adults and of children and adolescents with ADHD in a large national health plan. It also compared healthcare use and costs between those with and without ADHD.
A research team in the United States conducted an observational cohort study using claims data from more than 1.9 million adults and nearly 500,000 children and adolescents, comparing individuals diagnosed with ADHD to those without the diagnosis.
ADHD was diagnosed in 4% of adults and in 5% of children and adolescents.
Comorbidities By The Numbers:
Disruptive childhood disorders are behavioral problems marked by ongoing defiance, uncooperativeness, and aggression that affect a child's daily life and relationships. The main types, oppositional defiant disorder (ODD) and conduct disorder (CD), involve persistent anger and argumentativeness in ODD, and more severe actions like aggression, cruelty, and criminal behavior in CD. Without treatment, these common childhood disorders can continue into adulthood and raise the risks of substance use, violence, incarceration, and early death.
Disruptive childhood disorders were twenty times more frequent among children and adolescents with ADHD than among those without ADHD diagnosis, and fifteen times more frequent among adults with ADHD.
Bipolar disorder was twelve times more common among children and adolescents with ADHD than those without ADHD, and seven times more common among adults with ADHD.
Schizophrenia was eleven times more prevalent among children and adolescents with ADHD than those without ADHD, and three-and-a-half times more common among adults with ADHD.
Anxiety was nine times more frequent among children and adolescents with ADHD than among those without ADHD diagnosis, and more than five times more frequent among adults with ADHD.
Depression was eight times more common among children and adolescents with ADHD than those without ADHD, and more than five times more common among adults with ADHD.
Suicidal ideation was eight times more prevalent, and suicide attempt seven times more prevalent, among children and adolescents with ADHD than those without ADHD. Both suicidal ideation and suicide attempt were five times more common among adults with ADHD.
Gender dysphoria was almost six times more frequent among children and adolescents with ADHD than among those without ADHD diagnosis, and five times more frequent among adults with ADHD.
Eating disorders were over four times more common among children and adolescents with ADHD than those without ADHD, and five times more common among adults with ADHD.
Substance-related disorders were over six times more prevalent, and alcohol use disorder was six times more prevalent among children and adolescents with ADHD than those without ADHD, and four and three times more prevalent among adults with ADHD.
Increased Costs of Medical Care:
These comorbidities and ADHD led to higher medical costs. Children and adolescents with ADHD spent $610 more annually on healthcare than those without, while adults with ADHD had $1,684 higher average yearly expenditures than non-ADHD adults.
The Take-Away:
This large claims-based analysis of a national commercial insurer found ADHD diagnoses in roughly 4% of adults and 5% of children. It documented substantially higher rates of co-occurring behavioral-health conditions and markedly greater healthcare utilization and expenditures among those with ADHD. The authors report increased odds for several co-occurring diagnoses, as well as higher per-member-per-month (PMPM) spending and per-thousand-per-month (PTPM) utilization, largely driven by greater use of behavioral health services.
Importantly, these results come from cross-sectional, claims data within a commercially insured population: they describe associations, not causal relationships, and may not generalize to uninsured, publicly insured, or otherwise different populations. These findings, therefore, warrant cautious interpretation and highlight the need for longitudinal and more representative studies to clarify drivers of the increased burden and to inform care and policy.
Background:
Since the first in vitro fertilization (IVF) in 1978, assisted reproductive technology (ART) has led to over 10 million births worldwide.
There are four types of embryo transfers, depending on whether they are fresh or frozen, and on their developmental stage.
Fresh cleavage stage embryos are transferred on day 2 or 3 following fertilization and typically contain four to eight relatively large, undifferentiated cells. Fresh blastocyst embryos are transferred on day 5 or 6 after fertilization. At this point, they have developed over a hundred cells and have differentiated into two types: the inner cell mass, which develops into the fetus, and the outer cell layer, which forms the placenta.
Globally, more children are now born through assisted reproductive technology using frozen-thawed embryo transfer than fresh embryo transfer.
Research suggests that ART-conceived offspring may face increased risks of cardiovascular, musculoskeletal, chromosomal, urogenital diseases, and cancers. Might they also be at increased risk for ADHD?
Study:
Taiwan’s single-payer health insurance covers over 99% of people and records all their healthcare activity. Since 1998, it has kept an ART database for all couples registered for IVF treatment.
A Taiwanese research team reviewed all records for the five-year period from 2013 through 2017, ultimately analyzing 3,125 live singleton births from fresh cleavage stages, 1,332 from fresh blastocysts, 1,465 from frozen cleavage stages, and 4,708 from frozen blastocysts, alongside 878,643 naturally conceived singleton births.
The team controlled for the following potential confounders: pregnancy-induced hypertension, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, unhealthy lifestyle, placenta previa, placenta abruption, preterm premature rupture of membrane, and postpartum hemorrhage.
Results:
With these adjustments, cleavage stage embryo transfers, whether fresh or frozen, were associated with a seven-fold higher rate of ADHD diagnosis in offspring than natural conception.
Frozen blastocyst embryo transfers were likewise linked to a seven-fold increase in ADHD diagnoses in offspring compared to natural conception. Notably, fresh blastocyst transfers showed a 19-fold increase, likely due to the smaller number of cases in this category.
The team concluded, “Compared to natural conception, ART is associated with higher risks, particularly for preterm birth, ADHD, and developmental delay.”
Conclusion:
This large national cohort suggests that ART-conceived singletons face higher rates of several adverse outcomes, including preterm birth, ADHD, and developmental delay. Clinicians and prospective parents should therefore weigh these potential associations when counseling and planning care, prioritize optimized ART protocols and perinatal management, and ensure early developmental surveillance for ART-conceived children so concerns can be identified and addressed promptly.
It is important to note that the findings also point to the likely contribution of underlying parental infertility in these developmental outcomes. Future research should aim to disentangle parental- versus procedure-related risks to clarify absolute risk magnitudes. As always, associations of this time should not be interpreted as causal due to the inability of observational studies to rule out all possible confounding factors.
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