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Enteroviruses (EV) are a class of RNA viruses. This group of viruses includes some no-longer endemic forms such as polio and some serious but rare forms that cause encephalitis and meningitis. The most common virus in this population and period (1999-2003) was EV71, which can have complications, sometimes fatal, especially for children under five years old. It has also been linked to various chronic diseases, many of them neurological.

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Is it associated with the subsequent diagnosis of ADHD and, if so, to what extent?

Taiwan offers an excellent opportunity to study this in an entire population. This is because of its single-payer health care system. Its database "the National Health Insurance research database" covers 99.5 percent of the population.

The Taiwanese study team used a sub-database, the Longitudinal Health Insurance Database 2000, containing claims data from a million persons randomly sampled from the parent database.
From this database, the researchers identified over 49,000 EV patients. They excluded all who were 18 and older, were missing essential data or had been diagnosed with ADHD, epilepsy, topic diseases, coronary artery disease, stroke, rheumatoid arthritis, or systemic lupus erythematosus before being diagnosed with enterovirus. That left an EV cohort of 14,168,  who were matched with an equal number of non-EV individuals matched by age and sex.

After adjusting for age, sex, paternal occupation, and urbanization level of the residence, the EV cohort group was found to have a 25 percent greater risk for ADHD than the control group.

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Executive function(EF) is associated with the prefrontal cortex. It includes three core components: inhibitory control, cognitive flexibility, and working memory. Inhibitory control is the ability to avoid distractions, inhibit or control impulsive responses, and change to more thoughtful responses. Cognitive flexibility involves switching mental tasks or strategies, seeing problems from multiple perspectives, and identifying different ways of solving them. Working memory involves holding information in the mind ready for an ongoing processing.

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Persons with neurodevelopmental disorders, including ADHD, are known to have EF deficits relative to their normally-developing counterparts.

An international research team conducted a comprehensive search of the peer-reviewed medical literature to identify studies that have explored how physical activity affects those deficits in persons with neurodevelopmental disorders, specifically ADHD.

They identified 34 studies with 1,058 participants, of which 13 with 400 looked specifically at ADHD. There was substantial geographic diversity in the ADHD studies, spanning the globe: the United States, Canada, Switzerland, Taiwan, South Korea, Iran, Israel, and Tunisia.

Among the ADHD studies, a meta-analysis found physical activity improved executive functions overall, with a large effect size. More specifically, it included twelve tests of inhibitory control, four for working memory, three for cognitive flexibility, and one each for switching and planning (there was often more than one tester in the study).

There was no sign of publication bias. There was, however, substantial heterogeneity between studies. A further breakdown indicated substantial divergence by type of physical activity, with a large effect size for sports, medium effect sizes for aerobic exercise and motor skills training, and small effect size for exergaming (video games that are also a form of exercise).

Session time also made a big difference. Sessions at least an hour long had large effect sizes, those between 45 minutes and an hour had medium effect sizes, and shorter sessions had smaller effect sizes.
Improvements in inhibitory control had large effect sizes, those in cognitive flexibility had medium-to-large effect sizes, and those in working memory had small-to-medium effect sizes. All of which suggest ADHD patients can substantially improve executive functions through persistent and protracted physical exercise.

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Taiwan's National Health Insurance program is a single-payer system that covers 99.6% of the island's 23 million residents. It includes family relationships.

This enabled a Taiwanese study team to examine the comorbidity of psychiatric disorders among close relatives in the entire population over eleven years, beginning at the start of 2001 and concluding at the end of2011.

For greater certainty of diagnosis, only persons twice diagnosed with the same psychiatric disorder were included as index individuals. There were 431,887 index patients, 152,443 of whom were ADHD index patients.

These index patients were then compared with all of their first-degree relatives (FDRs): parents, children, siblings, and twins. This produced 1,017,430 patient-FDR pairs, of which 401,301 were ADHD patient-FDR pairs.

Next, four controls were matched by age, gender, and type relative to each case, resulting in 4,069,720 control pairs.

After adjusting for age, gender, urbanization, and income level, ADHD patients were seven times more likely than controls to have first-degree relatives with ADHD. They were also seven times more likely to have FDRs with major depressive disorder, four times more likely to have FDRs with autism spectrum disorder, twice as likely to have FDRs with bipolar disorder, and 80%more likely to have FDRs with schizophrenia.

An international team of researchers conducted a comprehensive search of the peer-reviewed literature to perform a meta-analysis, with three aims:

1) assess the global prevalence of adult ADHD

2) explore possible associated factors

3) estimate the 2020 global population of persons with adult ADHD.

In doing so, they distinguished between studies requiring childhood-onset of ADHD to validate adult ADHD (persistent adult ADHD) and studies that make no such requirement and examine ADHD symptoms in adults regardless of previous childhood diagnosis (symptomatic adult ADHD).

The search yielded forty articles covering thirty countries. Twenty reported prevalence data on symptomatic adult ADHD, 19 on persistent adult ADHD, and one on both. Thirty-five studies were published in the last decade (2010-2019). Thirty-one included both urban and rural populations. Thirty-five had a quality score of six or above (out of ten). Twenty-five had sample sizes greater than a thousand.

Because the prevalence of ADHD is age-dependent, and different countries vary widely in the age structure of their populations, the authors adjusted country results for their structures. This allowed for meaningful global estimates of the prevalence of adult ADHD.

Twenty studies covering a total of 107,282 participants reported the prevalence of persistent adult ADHD. The pooled prevalence was 4.6%. After adjustment for the global population structure, the pooled prevalence was 2.6%, equivalent to roughly 140 million cases globally.

Twenty-one studies covering 50,098 participants reported on the prevalence of symptomatic adult ADHD. The pooled prevalence was 8.8%. After adjustment for the global population structure, the pooled prevalence was 6.7%, equivalent to roughly 366 million cases globally.

For persistent adult ADHD, adjusted prevalence declined steeply from 5% among 18- to 24-year-olds to 0.8% among those 60 and older.

For symptomatic adult ADHD, adjusted prevalence declined less steeply from 9% among 18- to 24-year-olds to 4.5% among that 60 and older.

In each case, subgroup analyses found no significant differences based on sex, urban or rural setting, diagnostic tool, DSM version, or investigation period, although pooled prevalence estimates of persistent adult ADHD from 2010 onward were almost twice the previous pooled prevalence estimates. For symptomatic adult ADHD, however, differences between WHO (World Health Organization) regions were highly significant, although the outliers(Southeast Asia at 25% and Eastern Mediterranean at 16%) were based on small samples(304 and 748 respectively).

In both cases, between-study heterogeneity was very high (over 97%). The authors noted, "the age of interviewed participants in the included studies was not unified, ranging from young adults to the elderly. Given the fact that the prevalence of adult ADHD decreases with advancing age, as revealed in previous investigations and our meta-regression, it is not surprising to observe such a diversity in the reported prevalence, and the considerable heterogeneity across included studies could not be fully ruled out by a priori selected variables, including diagnostic tool, DSM version, sex, setting, investigation period, WHO region, and WB [World Bank] region. The effects of other potential correlates of adult ADHD, such as ethnicity, were not able to be addressed due to the lack of sufficient information."

In both cases, there was also evidence of publication bias. The authors stated, "we did not try to eliminate publication bias in our analyses, because we deemed that an observed prevalence of adult ADHD that substantially differed from previous estimates was likely to have been published."

The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for the first six months of infancy and continuation of breastfeeding for at least a year thereafter. Yet less than a third of U.S. mothers are still breastfeeding their infants at 12 months.

Previous studies have suggested that breastfeeding is associated with a lower risk of ADHD. But sample sizes have been small, and have not sufficiently explored confounding factors.

Using the Centers for Disease Control and Prevention's 2011-2012 National Survey of Children's Health, a research team analyzed data from a representative U.S. sample of 12,793 three- to five-year-old children.

The team excluded children with autism, developmental delays, speech problems, Tourette syndrome, epilepsy or seizure disorder, hearing problems, non-correctable vision problems, bone/joint/muscle problems, brain injury/concussion, or any current behavioral/conduct problems other than ADHD.

The team also adjusted for potential confounders. Some were demographic: sex, age, race, household income, the number of adults older than 18 years of age living in the home, and the number of children younger than the age of 18 years living in the home. Other variables related to health care access and delivery: insurance type, consistency of health insurance in the past 12 months, and a composite variable reflecting having a primary care provider, getting needed referrals, and effective care coordination. Exposure to secondhand smoke and preterm births were other key variables.

In the fully adjusted results, children who had been breastfed for at least six months were 62% less likely to be diagnosed with ADHD than those who had not (p = .0483). Moreover, each month of breastfeeding duration was associated with a significant additional 8% reduction in the odds of an ADHD diagnosis (95% confidence interval from 1% to 14%).

The authors concluded, "Preschool children who were never breastfed as infants were much more likely to have a medical diagnosis of ADHD than were children who were exclusively breastfed. Moreover, there seems to be a continuum of neuroprotective benefits associated with breastfeeding duration. Although these analyses cannot establish a causal relationship, our findings add to a growing body of literature-including several longitudinal studies and a meta-analysis-that suggests breastfeeding may reduce the likelihood of a child having later problems with inattention and/or hyperactivity. Although follow-up studies are needed to further examine the relationship between infant feeding and ADHD, these findings provide evidence to support the neurodevelopmental benefits of breastfeeding."

This systematic review of the literature identified seven studies addressing ADHD and sexuality.

Sexual function

A Dutch study compared 136 persons with ADHD with two large surveys of the general Dutch population. They used both a self-report questionnaire, the Questionnaire for screening Sexual Dysfunction and a non-validated questionnaire especially constructed for the study. They found that males with ADHD reported a 50 percent higher rate of frequent masturbation than males in the general population. Both males and females were less than half as likely to be satisfied with their sex life. That was almost certainly linked to the fact that ADHD participants in the sample were less likely to be in a relationship.

A second study compared 79 ADHD participants with controls. Using a validated questionnaire, the Diagnostic Interview Schedule, to assess sexual function, they found a significant positive correlation between ADHD and the items "sex drive more than the average" and "recurrent thoughts about sex' by comparison with the control group.

A third study used two validated inventories “ the Derogates Sexual Functioning Inventory and the Social Sexual Orientation Inventory“ to assess sexual function among 27 young adult males. They found their sex drive to be higher than in the control group. 

Another study, also with 27 ADHD patients, compared them with two other groups, one with fiber mitosis (benign connective tissue cancers), and the other with both ADHD and fibromatosis. They used the validated Life Satisfaction Questionnaire to assess sexual function and found that those with ADHD reported lower sex life satisfaction.

On the other hand, the only large study, with over 14,000 participants, using a non-validated questionnaire to assess sexual function, found negligible associations between ADHD and the number of sexual partners, the frequency of having sex with one's partner, and the frequency of masturbation.

Sexual dysfunctions

The Dutch study mentioned above, comparing 136 ADHD outpatients with two large surveys of the general Dutch population, used a validated self-report questionnaire, the Questionnaire for screening Sexual Dysfunctions, and a non-validated questionnaire, specially designed for the study, the Questionnaire for screening Sexual Problems. It found the rate of sexual dysfunction among both males and females with ADHD to be over twice the level in the general population. Men were four times as likely to report problems with orgasm, 50 percent more likely to report premature ejaculation, and over ten times as likely to report sexual aversion. Women were over three times as likely to report sexual excitement problems, over twice as likely to report problems with orgasm, and over three times as likely to report sexual aversion. No significant differences existed between patients treated with psychostimulants and those without such treatment.

A second study, which used a validated questionnaire to compare 79 ADHD participants with controls, found significant correlations between ADHD and aversion to sex for men but none for women.

On the other hand, a third study, comparing 32 subjects with ADHD with 293 controls, found no significant difference in the prevalence of sexual dysfunctions. It used clinical interviews to assess ADHD, and a non-validated questionnaire to assess sexual dysfunctions.

A fourth study took a very different approach. It compared 38 individuals with premature ejaculation to 27 controls. It found more than ten times the rate of ADHD symptoms among those with premature ejaculation than in the control group. Significantly, it measures premature ejaculation directly, with a stopwatch.

Conclusion

The authors concluded, "This article provides the first systematic review of sexual health among subjects with ADHD and shows that the quality of sexual health among subjects with ADHD seems poor," but acknowledged "several limitations to our review. There are only a few studies for the topics we reviewed. For many studies, the sample size was small. The methodology and measurement instruments differed, which created a potential bias."

Indeed, the study with the largest sample size found negligible associations between ADHD and sexual function, contradicting studies with small sample sizes.

Only four of the studies, all with small sample sizes, examined sexual dysfunctions. Two found strong associations with ADHD, one found none, and the fourth had mixed results.

This points to a compelling need for further research on ADHD and sexuality, with larger sample sizes.

Proper development of the gut biota is important for the health of the brain and nervous system. It has been hypothesized that disturbances of gut bacteria by antibiotics could contribute to the development of neurodevelopmental disorders, including ADHD.

In the case of ADHD, studies to date have produced conflicting results. To tease out any familial confounding reflecting shared environment and genetics, a joint Dutch-Swedish team of researchers further tested the hypothesis through 7- to 12-year-old twins in the Netherlands Twin Register (25,781 twins) and 9-year-old twins in the Swedish Twin Registry (7,946 twins).

ADHD symptoms in the Netherlands cohort were derived from mothers' answers to the short Conners' Parental Rating Scale-Revised. For the Swedish cohort, ADHD was determined through the International Classification of Diseases codes for ADHD in the cross-linked National Patient Register.

Exposure to antibiotics during the first two years of childhood was determined by parent reports for the Netherlands twin cohort, and by prescription claims for antibiotics in the Swedish twin cohort.

Covariates were explored in both twin cohorts including educational attainment of parents, gender of the infant, birth weight, delivery mode, and asthma. Breastfeeding was also explored in the Dutch cohort.

In the unmatched analysis, comparing children with ADHD with non-related children without ADHD, early-life antibiotic use was associated with a significant 8% greater odds of ADHD in the Netherlands cohort and a significant 14% greater odds of ADHD in the Swedish cohort.

However, when limiting the analysis to matched monozygotic twins, the association disappeared altogether in both the Dutch and Swedish cohorts. Pooling both cohorts resulted in the same outcome. In all three cases, the odds flipped into a mildly negative association, but with no statistical significance.

Using higher cutoff values for ADHD symptoms made no difference.

The authors concluded, "In this large co-twin study performed in two countries, early-life antibiotic use was associated with increased risk of ADHD and ASD, but the results suggest that the association disappeared when controlled for shared familial environment and genetics, indicating that this association may be susceptible to confounding. Our results indicate that there is no association between ADHD and ASD diagnoses and early antibiotic use when environmental and genetic family factors are taken into account."

Taiwan's National Birth Registration database tracks every birth. Using all entries from 2005, random sampling was used to create the Taiwan Birth Cohort Study of 24,200 mother-infant pairs, which were geographically distributed and represented 12 percent of all births.

As this was an eight-year longitudinal study, there were dropouts, and 17,256 pairs completed the study. After excluding cases with fetal distress, smoking or alcohol use during pregnancy, and missing information on covariates, the final study population was 16,376.

Participants' addresses during gestation were geocoded to the township level, and local air pollution data was retrieved for the years 2004 to 2006 from air quality monitoring stations administered by Taiwan's Environmental Protection Administration. Every hour, each station records levels of nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulfur dioxide (SO2), carbon monoxide (CO), and particulate matter of diameter 10 μm or less (PM10).

The Taiwanese research team addressed several potential confounding factors: sex, maternal age, delivery method (cesarean section or not), birth in summer (June-August), urban or rural residence, and annual household income.

Because ADHD is primarily observable as hyperactivity rather than inattention among young children, the team focused on relating symptoms of hyperactivity to levels of air pollutants.

After adjusting for covariates, the team found no significant association between PM10 and SO2 levels and hyperactivity disorder. Nitrogen oxide levels, on the other hand, were associated with more than 25 percent higher odds of hyperactivity.

Breaking that down further, they found no significant association with NO2, and that the 25 percent higher odds were exclusive with nitric oxide (NO), a pollutant emitted by internal combustion engines in cars, trucks, and busses. NO is a free radical, meaning it has an unpaired electron that can damage the body because of its strong chemical reactivity.

The authors noted, "Our study has some limitations. First, hyperactivity was diagnosed based on a parent-reported physician or specialist diagnosis. Although we did not inquire which specialists made these diagnoses, they must have been a pediatrician, psychiatrist, or special education teacher. ... Second, the calculated exposure to ambient air pollutants was not an accurate personal exposure because it did not take indoor air pollutant levels and time-activity patterns into consideration. Applying personal environmental monitoring in such a large sample is impractical, especially when the subjects are pregnant."

Nevertheless, they emphasized, "this is the first study attempting to discover which component of NOx is more critical to the development of hyperactivity in offspring."