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A commonly reported risk associated with ADHD medication is reduced growth in height. But studies to date have generally not adequately described or measured possible confounders, such as genetic factors, prenatal factors, or socioeconomic factors. What if ADHD were associated with reduced height even in the absence of medications? 

An international study team explored this question by performing a nationwide population study comparing data from before (1968-1991) and after (1992-2020) the adoption of stimulant therapy for ADHD in Sweden. 

The country’s single-payer health insurance system that connects patient records with all other national registers through unique personal identification numbers makes such analysis possible. Sweden also has military service conscription, which records the heights of 18-year-old males.

The participants were all 14,268 Swedish males with a diagnosis of ADHD who were drafted into military service at any time from 1968 through 2020. 

Up to five non-ADHD controls were identified for each ADHD case, matched by sex (they had to be male), birth year, and county. The total number of controls was 71,339.

Among 34,586 participants in the period before adoption of stimulant medications (1968-1991), those diagnosed with ADHD had roughly 30% greater odds of being shorter than normal (166-172 vs. 173-185 cm) than typically developing controls. That dropped to 20% greater odds among the 34,714 participants in the cohort following adoption of stimulant medications.

The odds of those diagnosed with ADHD being much shorter than normal (150-165 vs. 173-185 cm) remained identical (about 55% greater) among the almost 30,000 participants in both cohorts.

In other words, there was no increase in the odds of ADHD individuals being shorter than normal after adoption of stimulant therapy in Sweden compared with before such adoption.

Furthermore, after adjusting for known confounders, including birth weight, inflammatory bowel disease, celiac disease, hypothyroidism, anxiety disorders, depression, substance use disorder, and highest parental education, the odds of those diagnosed with ADHD being shorter than normal or much shorter than normal in the 1992-2020 cohort dropped to roughly 10% and 30% greater, respectively.

Could it be the disorder itself rather than stimulant treatment that is associated with reduced height in individuals diagnosed with ADHD?

To address effects of environmental and familial/genetic confounding, the team then compared the entire cohort of males diagnosed with ADHD from 1968 through 2020 with typically developing male relatives, ranging from first cousins to full siblings.

Among full siblings, the odds of those with ADHD diagnoses being shorter (over 90,000 participants) or much shorter (over 77,000 participants) were a statistically significant 14% and 18%, respectively.

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The authors concluded, “Our findings suggest that ADHD is associated with shorter height. On a population level, this association was present both before and after ADHD-medications were available in Sweden. The association between ADHD and height was partly explained by prenatal factors, psychiatric comorbidity, low SES [socioeconomic status] and a shared familial liability for ADHD.”

In the general population, most mothers experience mood disturbances right after childbirth, commonly known as postpartum blues, baby blues, or maternity blues. Yet only about one in six develop symptoms with a duration and magnitude that require treatment for depressive disorder, and one in ten for anxiety disorder.

To what extent does ADHD contribute to the risk of such disorders following childbirth? A Swedish study team used the country’s single-payer health insurance database and other national registers to conduct the first nationwide population study to explore this question.

They used the medical birth register to identify all 420,513 women above 15 years of age who gave birth to their first child, and all 352,534 who gave birth to their second child, between 2005 and 2013. They excluded miscarriages. They then looked for diagnoses of depression and/or anxiety disorders up to a year following childbirth.

In the study population, 3,515 mothers had been diagnosed with ADHD, and the other 769,532 had no such diagnosis. 

Following childbirth, depression disorders were five times more prevalent among mothers with ADHD than among their non-ADHD peers. Excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

Similarly, anxiety disorders were over five times more prevalent among mothers with ADHD than among their non-ADHD peers. Once again, excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

The team cautioned, “There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.”

Nevertheless, they concluded, “ADHD is an important risk factor for both depression and anxiety disorders in the postpartum period and should be considered in the post- pregnancy maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders. Parental education prior to conception, psychological surveillance during, and social support after childbirth should be provided to women diagnosed with ADHD.”

Noting that previous “systematic reviews concluded that currently available data on the clinical effectiveness of acupuncture for treating ADHD are yet to be sufficient to support its routine use,” a South Korean study team conducted an updated systematic search of the medical literature for randomized controlled trials (RCTs) comparing acupuncture with drug treatment for children and adolescents with ADHD. There were no restrictions on language or publication type.

Only two of the meta-analyses involved more than two RCTs. 

One of them, of six RCTs with a combined 541 participants, reported total treatment efficacy of acupuncture to be at least equal to that of conventional treatment with ADHD medicines. 

Another, of five RCTs with a total of 351 participants, reported total treatment efficacy of combined acupuncture and ADHD drugs to be at least equal to that of conventional treatment with ADHD medicines.

Two RCTs with a Noting that previous “systematic reviews concluded that currently available data on the clinical effectiveness of acupuncture for treating ADHD are yet to be sufficient to support its routine use,” a South Korean study team conducted an updated systematic search of the medical literature for randomized controlled trials (RCTs) comparing acupuncture with drug treatment for children and adolescents with ADHD. There were no restrictions on language or publication type.

Only two of the meta-analyses involved more than two RCTs. 

One of them, of six RCTs with a combined 541 participants, reported total treatment efficacy of acupuncture to be at least equal to that of conventional treatment with ADHD medicines. 

Another, of five RCTs with a total of 351 participants, reported total treatment efficacy of combined acupuncture and ADHD drugs to be at least equal to that of conventional treatment with ADHD medicines.

Two RCTs with a combined 152 participants reported a large effect size improvement in hyperactivity/impulsivity symptoms from acupuncture treatment versus conventional drug treatment.

From this one could superficially conclude that acupuncture is at least as effective for treating ADHD as the medicines currently considered to be the standard of care, and that there is no need to combine acupuncture with drug treatment.

However, there were numerous methodological shortcomings:

• No effort was made to look for publication bias.
• There were few RCTs, and the combined number of participants was relatively small.
• Only one of the six RCTs in the first meta-analysis and none of the five RCTs in the second meta-analysis was rated “low risk of bias.”
• Though nowhere stated in the journal article, there may have been cultural bias as well. All studies included in the meta-analyses were conducted in China. As China has emerged as a global superpower, it has been eager to portray its traditional medicine as at least equal if not superior to forms of medicine originating elsewhere.
• The authors noted, “the quality of the studies included in this systematic review was poor. Assessing the blinding of studies is a major aspect in determining the risk of bias of a study, but most of the studies did not provide any relevant information.” 

The authors concluded, “The current evidence on AT [acupuncture treatment] is still too limited to support its routine use in treating ADHD.”

152 participants reported a large effect size improvement in hyperactivity/impulsivity symptoms from acupuncture treatment versus conventional drug treatment.

From this one could superficially conclude that acupuncture is at least as effective for treating ADHD as the medicines currently considered to be the standard of care, and furthermore that there is no need to combine acupuncture with drug treatment.

However, there were numerous methodological shortcomings:

• No effort was made to look for publication bias.
• There were few RCTs, and the combined number of participants was relatively small.
• Only one of the six RCTs in the first meta-analysis and none of the five RCTs in the second meta-analysis was rated “low risk of bias.”
• Though nowhere stated in the journal article, there may have been cultural bias as well. All studies included in the meta-analyses were conducted in China. As China has emerged as a global superpower, it has been eager to portray its traditional medicine as at least equal if not superior to forms of medicine originating elsewhere.
• The authors noted, “the quality of the studies included in this systematic review was poor. Assessing the blinding of studies is a major aspect in determining the risk of bias of a study, but most of the studies did not provide any relevant information.” 

The authors concluded, “The current evidence on AT [acupuncture treatment] is still too limited to support its routine use in treating ADHD.”

Using Statistics New Zealand’s Integrated Data Infrastructure (IDI), a large database of linked de-identified administrative and survey data about people and households, a local study team examined a three-year birth cohort (mid-1992 through mid-1995) totaling 149,076 persons.

The team assessed the presence of ADHD within this cohort through diagnosis codes and inference from medication dispensing, where there was at least one code relating to an ADHD diagnosis in the medication datasets. This subgroup consisted of 3,975 persons.

Next, they related this information to criminal justice system interactions of increasing severity, starting with police proceedings, and continuing with court charges, court convictions, and incarcerations. These interactions were tracked during an eight-year period from participants’ 17th birthday through their 25th birthday.

In this same period the team also tracked types of offenses: against people; against property; against organizations, government, and community; and violent offenses.

In all cases, the study team adjusted for gender, ethnicity, deprivation, and area of residence as potential confounders. 

With these adjustments, young adults with ADHD were over twice as likely as their typically developing peers to be proceeded against by police, to be charged with an offense, and to be convicted. They were almost five times as likely to be incarcerated. 

With the same adjustments, young adults with ADHD were over twice as likely as their typically developing peers to be convicted of offenses against organizations, government, and community. They were almost three times as likely to be convicted of crimes against persons, and over three and a half times more likely to be convicted of either violent offenses or offenses against property.

The authors noted, “The greater effect size for incarceration observed in our study may be due to the lack of control for comorbid conditions such as CD [conduct disorder], which are known criminogenic risk factors.” 

They also noted, “The sharp increase in the risk of incarceration observed may also signal differences in the NZ justice system’s approach to ADHD, which may be less responsive to the condition than other nations, particularly the steps in the justice system between conviction and sentence. This would suggest that the UNCRPD [United Nations Convention on the Rights of Persons with Disabilities] obligations of equal recognition before the law and the elimination of discrimination on the basis of disability are not being met for individuals with ADHD in NZ.”

They concluded, “Our findings revealed that not only were individuals with ADHD overrepresented at all stages of the CJS [criminal justice system] and offense types examined, there was also a pattern of increasing risk for CJS interactions as these individuals moved through the system. These results highlight the importance of early identification and responsivity to ADHD within the CJS and suggest that the NZ justice system may require changes to both of these areas to ensure that young individuals with ADHD receive equitable access to, and treatment within, the CJS.”

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.”

Sex chromosome abnormalities are replication errors that produce an atypical number of sex chromosomes.  Most people have 23 pairs of chromosomes for a total of 46.  One pair is called the sex chromosome pair.  It is either XX (for biological females) or XY (for biological males).  The term 46,XY refers to a typical biological male and the term 46,XX refers to the typical biological female.  

In rare cases a person may have only 45 chromosomes due to having only one sex chromosome, the X chromosome (45,X).  Some people, rarely, have an extra sex chromosome and are designated: 47,XXX, 47,XXY, and 47,XYY.  These rare sex chromosome differences occur in between 0.5 and 1.3 per 1,000 livebirths. 

These differences have physical manifestations. For example, 45,X is associated with shorter height and abnormal development of the ovaries. The other three are associated with greater height. 47,XXX is associated with premature ovarian failure and 47,XXY with low testosterone.

A Danish and U.S. team used data from Denmark’s single-payer universal health insurance system to assess the association of these sex chromosome differences with the prevalence of ADHD.

They performed a case-cohort study. The source population was all 1,657,449 singleton births in Denmark between May 1, 1981, and Dec 31, 2008. The cases consisted of all 93,608 individuals in this population who were diagnosed with any of five psychiatric disorders, including ADHD. These were compared with a cohort consisting of 50,615 individuals randomly selected from the source population.

The combined population prevalence of these four sex chromosome differences was 1.45 per 1,000. 47,XXY was the most common, at 1.23 per 1,000, followed by 47,XYY at .82 per 1,000, then 47,XXX at .66 per 1,000. 45,X was by far the least common, at less than .23 per 1,000.

All four conditions were associated with significantly increased risk of ADHD:

• 47,XXY roughly doubled the risk. 
• 47,XXX increased the risk 2.5-fold.
• 47,XYY more than quadrupled the risk.
• 45,X more than sextupled the risk.

These data are intriguing because we know there  are sex differences in the prevalence of ADHD but the causes of those differences are unknown.  

Given that ADHD is more common in boys than girls, one would have predicted that having an extra Y chromosome would increase risk for ADHD.  That is the case here but we also see that having an extra X chromosome also increases risk, which means that the impact of sex chromosomes on ADHD is not straightforward.

Infants begin to transition from breast or formula milk to solid food at about six months of age, as they gradually develop interest in food and the ability to chew.

The American Academy of Pediatrics recommends breastfeeding for the first six months. The European Society of Pediatric Gastroenterology Hepatology and Nutrition recommends initiation of supplementary food around that time. The World Health Organization (WHO) has set a 2025 goal of getting most mothers worldwide to breastfeed exclusively through the first six months of infancy.

Noting that “inconsistent findings have been reported in previous national survey-based studies,” a South Korean study team conducted a nationwide population study to explore the relationship between breastfeeding and subsequent rates of ADHD.

South Korea has a mandatory single-payer national health insurance system – the National Health Insurance Service (NHIS) – that covers virtually the entire population. Detailed and consistent NHIS records facilitate nationwide population studies. 

One NHIS program is the National Health Screening Program for Infants and Children (NHSPIC), which includes periodic examinations by trained pediatricians up to six years of age.

Using these national records, the team identified a cohort of over 1.1 million infants. These same records show that a little over a third (36%) received nothing but formula milk feeding during their first six months. About a fifth (21%) received a mix of formula and breast feeding. Almost a half (43%) were exclusively breastfed.

ADHD diagnoses were made by physicians during hospital visits.

The team adjusted for a series of confounders that were found to influence outcomes: sex, year of examination, residence, socioeconomic status, preterm birth, birth weight, and body measurements (weight, microcephaly) at examination (4–6 months of age).

With these adjustments, partial breastfeeding was associated with a small but significant (9%) reduction in the odds of infants later being diagnosed with ADHD, relative to infants receiving only formula milk feeding.

Exclusive breastfeeding was associated with a much larger 23% reduction in the odds of infants later being diagnosed with ADHD, relative to exclusive formula feeding.

What’s especially noteworthy is the dose-response pattern that suggests that breastfeeding may have a protective effect. 

A separate analysis comparing infants who began transitioning to supplementary solid food before versus after six months found absolutely no difference in the odds of subsequently being diagnosed with ADHD.

A similar pattern emerged for autism spectrum disorder on all counts, again reflecting a dose-response pattern, pointing to what may be a broader beneficial effect of breastfeeding for healthy neurologic development.

The team concluded, “The risk of ADHD and ASD [autism spectrum disorder] considerably decreased with breastfeeding, and this tendency was more prominent in children who received EBF [exclusive breastfeeding] than in those who received PBF [partial breastfeeding]. Our study strengthens and supports the idea that breastfeeding is beneficial in preventing NDDs [neurodevelopmental disorders] in children. We suggest that breastfeeding be encouraged and recommended to promote good neurodevelopmental outcomes.”

Noting that “The efficacy of surface electroencephalographic neurofeedback (EEG‐NF) for improving attentional performance assessed by laboratory measures in patients with attention‐deficit/hyperactivity disorder (ADHD) remains unclear,” a Taiwanese study team systematically searched seven databases, including the U.S. clinical trials database, for randomized controlled trials (RCTs) through January of 2022.

They identified fourteen RCTs with a combined 718 participants that met criteria for inclusion in meta-analysis. The net outcome was a small-to-medium effect size improvement in attentional performance for participants receiving EEG neurofeedback by contrast with “comparators.” 

The comparators varied widely: waitlist, treatment as usual, physical exercise, behavioral therapy, attention skills training, computer-aided attention training, medications, electromyographic biofeedback, sham EEG neurofeedback. This alone brings into question the meta-analysis outcome.

But there were additional methodological shortcomings. There was strong evidence of publication bias. And though the authors promised, “On encountering funnel plot asymmetry, potentially missing studies were imputed by using the Duval and Tweedie’s trim and fill method,” they never shared the outcome.

Another shortcoming was that only two of the fourteen RCTs blinded the participants, meaning that in twelve RCTs the participants were likely to be aware they were in the EEG neurofeedback group rather than the control group. And that made all the difference. The twelve unblinded RCTs were responsible for all the small-to-medium effect size improvement. There was no sign of improvement in the two blinded RCTs.

The authors tried to give a positive spin to these results, stating “our results supported the use of surface EEG-NF for improving attentional performance through the modulation of basic neurocognitive functioning in patients with ADHD,” while conceding, “However, given the small number of trials and the poor methodological qualities regarding blinding, our findings need to be judiciously interpreted and warrant further investigations for validation.”

A more candid assessment of this meta-analysis would be the one they began with: “The efficacy of surface electroencephalographic neurofeedback (EEG‐NF) for improving attentional performance assessed by laboratory measures in patients with attention‐deficit/hyperactivity disorder (ADHD) remains unclear.”

Virtual reality consists of computer-generated simulated environments. These can be on a flat screen as on a computer or tablet, in which the viewer’s peripheral vision is unimpaired. These types of virtual reality are non-immersive. Where vision of the outward actual environment is blocked, as by goggles, virtual reality becomes immersive.

A Romanian and British trio of researchers embarked on a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore whether immersive virtual reality interventions are effective at improving cognitive deficits in children and adolescents with ADHD, what factors influence effect sizes, and whether such interventions are safe and likely to be adhered to by patients.

They distinguished between RCTs with passive control groups using either no treatment or waiting list, and RCTs using an active comparator group, where participants received an intervention with similar levels of contact with research personnel and a similar number of sessions as the intervention group (e.g., psychotherapy or non-immersive VR). Medication was also classified as an active comparator group.

A meta-analysis of seven RCTs with a combined 321 participants found that across all outcome measures, immersive virtual reality interventions were associated with large effect size improvements in cognitive functioning. Correcting for publication bias maintained the finding of large effect size improvements. Variation (heterogeneity) between studies was moderately high, but the mean outcome in every RCT was likewise positive though not always statistically significant.

A second meta-analysis of six RCTs totaling 273 persons likewise found large effect size improvements on attention measures. Again, heterogeneity was moderately high, but the mean outcome in every RCT was likewise positive though not always statistically significant.

There was no significant difference in outcomes between RCTs with active controls and those with passive controls. Nor did newer vs. older VR technology make any difference. Likewise, formal ADHD diagnosis vs. participants with ADHD-like symptoms but no formal diagnosis had no significant effect on outcomes.

The authors concluded, “immersive VR-based interventions are effective at improving global cognitive functioning, attention, and memory in children with ADHD compared with controls. Moreover, immersive VR is feasible in terms of treatment adherence and a safe cognitive rehabilitation tool.” 

But they noted, “Results should be cautiously interpreted given the poor quality of included studies and small sample.”

Children with disabilities are known to be at heightened risk of violence compared to their non-disabled peers. To what extent does this hold true for ADHD?

Denmark has a single-payer health insurance system through which health data about virtually the entire population can be cross-referenced with population, crime, welfare, and other registers through unique individual person numbers.

A Danish study team accessed national registers to examine the relationship between ADHD and criminal victimhood among nine yearly birth cohorts totaling more than 570,000 children and adolescents. 

Of these, 557,521, among them 12,040 with ADHD, were not reported as being exposed to violence, and 12,830, among which 1,179 with ADHD, were exposed to violence.

From the raw data, children and adolescents with ADHD were more than four times as likely to be exposed to violence than their typically developing peers.

The team then adjusted for other disabilities, family risk factors, gender, birth year, and ethnic background.

With these confounders out of the way, children and adolescents with ADHD remained more than twice as likely to be exposed to violence than their typically developing peers.

To place this outcome in further perspective:

• Brain injuries increased the odds of being exposed to violence by over 75% relative to typically developing peers.
• Physical and speech disabilities raised the odds by a bit over 35%.
• Intellectual and sensory disabilities, dyslexia, and congenital malformations had no effect. 
• Epilepsy reduced the odds of being exposed to violence by just under 20%, and autistic spectrum disorder by just over 25%.

Certain family risk factors further aggravated the odds:

• Violence in the family by more than 2.5-fold.
• Out-of-home care and breakup of parental relationship by more than 75%.

Perhaps surprisingly, substance abuse by family members had no effect whatsoever after adjusting for confounders.