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Noting that "despite a lack of solid evidence for their use, rTMS [repetitive transcranial magnetic stimulation]and tDCS [transcranial direct current stimulation] are already offered clinically and commercially in ADHD," and that a recent meta-analysis of ten tDCS studies found small but significant improvements in outcomes, but had several methodological shortcomings and did not include two studies reporting mostly null effects, a team of British neurologists performed a meta-analysis of all twelve sham-controlled, non-open-label, studies found in a comprehensive search of the peer-reviewed literature.

Ten of the twelve randomized-controlled trials used anodal stimulation of the dorsolateral prefrontal cortex, while the other two used anodal stimulation of the right inferior frontal cortex.

The trials explored several measures of cognition. The research team carried out a meta-analysis of all twelve trials, with a total of 232 participants, and found no significant improvement in attention scores from CDC, relative to sham stimulation. A second meta-analysis, of eleven trials with a total of 220 participants, assessed the efficacy of tDCS on improving inhibition scores, and again found no significant effect. A third meta-analysis, encompassing eight trials with a total of 124 participants, evaluated the efficacy of tDCS on improving processing speed scores, once again finding no significant effect.

The latter two meta-analyses approached the border of significance, prompting the authors to speculate that larger sample sizes could bring the results just over the threshold of significance. Even so, effect sizes would be small.

It is also possible that the trials focused on regions of the brain suboptimal for this objective, and thus the authors "cannot rule out the possibility that stimulation of other prefrontal regions (such as the right hemispheric inferior frontal cortex or dorsolateral prefrontal cortex or parietal regions), multiple session tDCS or tDCS in combination with cognitive training could improve clinically or cognitive functions in ADHD."

As to concerns about safety, on the other hand, "stimulation was well-tolerated overall."

The authors concluded that based on current evidence, tDCS of the dorsolateral prefrontal cortex cannot yet be recommended as an alternative Neurotherapy for ADHD.

Spontaneous abortion is the medical term used for what is more commonly known as miscarriage. It means the unintended loss of an embryo or fetus before the 20th week of pregnancy. This must not be confused in any way with induced abortion, which is a deliberate and intentional act to terminate a pregnancy.

Most miscarriages occur when the fetus is not developing properly. Among the major causes of miscarriage are chromosomal abnormalities, birth defects, abnormal hormonal imbalances, infections, and exposure to toxins.

A team of Chinese researchers used the Danish national registers to explore a nationwide cohort for associations between previous miscarriage and ADHD in subsequent offspring. They included all 1.1 million births in Denmark over the 17 years from 1995 through 2012. They excluded all children with chromosomal abnormalities, those born either extremely early (after less than 22 weeks gestation) or extremely late (greater than 45 weeks), and those for whom this information was missing. That left over one million children in the study cohort.

The team classified children as having ADHD either based on a recorded hospital diagnosis or after receiving ADHD medication prescriptions at least twice after the age of 3 years. A total of 25,747 children were identified as ADHD individuals (554 mothers having at least two miscarriages, 3,087 mothers having one miscarriage, and 22,106 mothers without miscarriage). The average age of the first ADHD diagnosis was 10 years.

Just over 130,000 children (12.2%) were born to mothers who had at least one miscarriage. Of these, just under 113,000 (10.6%) were born to mothers with a single miscarriage before birth, and just over 17,000 to mothers with more than one prior miscarriage.

Based on previous research, the team identified potential confounders, including sex, preterm birth (less than 37 weeks), low birth weight, small for gestational age, low Agar score (performed right after birth to assess the risk of infant mortality), maternal and paternal ages at birth, maternal diabetes, maternal hypothyroidism, maternal smoking during pregnancy, maternal education level, maternal and paternal psychiatric disorders before birth.

After adjusting for these possible confounders, children of mothers with a single prior miscarriage were 9% more likely to develop ADHD than those of mothers without any miscarriage. Children of mothers with two or more prior miscarriages were 22% more likely to be diagnosed with ADHD. This upward exposure-response trend was statistically significant.

Preterm birth was found to be the strongest confounding mediator of this trend but accounted for under 4% of the association. The authors concluded, "the observed associations were independent of several factors, such as maternal socioeconomic status, type of spontaneous abortion, parental history of psychiatric disorders, pregnancy characteristics (maternal smoking status, infection, diabetes and hypothyroidism status during pregnancy)and birth outcomes (low birth weight, preterm birth, low Agar score, and small for gestational age)."

They also noted that given the frequency of miscarriages, affecting more than one in eight women, "a small increase of neurodevelopmental problems in offspring could have major public health implications."

A key aspect of ADHD is greater difficulty controlling urges, so it is no surprise that there is a strong association between ADHD and substance use disorders, and opioid addiction in particular. It's also known that stimulants are effective in reducing ADHD symptoms. That would suggest that ADHD patients being treated for opioid addiction should also be treated for ADHD.

How extensive is such complementary treatment? A Norwegian research team used national register data from the Norwegian Prescription Database to find out. They began by identifying all 9,235 individuals who were dispensed at least one opioid agonist prescription from 2015 through 2017.

Opioid agonists, such as methadone and buprenorphine (Suboxone), while opioids have properties that prevent withdrawal and reduce cravings. They can do this precisely by substituting a less dangerous slow-acting opioid for a more dangerous rapid-acting one. They are also less addictive because they do not generate the intense highs of fast-acting opioids. That greatly reduces the risk of overdose, and risk of relapse to more hazardous opioid use, and promotes connections with the professional healthcare sector.

About 7,500 Norwegians are undergoing opioid agonist therapy at any given time. During the three-year study period, roughly three out of four were dispensed buprenorphine and the remainder methadone.

Although somewhere around one in five patients on opioid agonist therapy have ADHD (estimates range from11 to 33%), the team found that less than one in twenty were also dispensed ADHD medication. In 2015, only 3.5 percent received ADHD medication, rising slightly to 4.6 percent in 2017. In 2017, 62 percent received methylphenidate, 42 percent received various amphetamines, and only five percent received non-stimulant atomoxetine (there was some overlap).

Patients on buprenorphine were 60 percent more likely to be dispensed ADHD medications than those on methadone.

The authors concluded, "Co-prescribing of CAS [centrally acting stimulant] and atomoxetine was low in the OAT [opioid agonist therapy] population in Norway, relative to the expected prevalence of ADHD in this patient group. Considering that up to a third of the OAT population is estimated to have ADHD, only 3.5 to 4.6% of patients received both ADHD medication and OAT opioids in Norway in the period from 2015 to 2017. Randomized-controlled trials evaluating ADHD medication in different doses are needed to improve the treatment of ADHD in the OAT population."

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."