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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.”

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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.”

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OptumLabs Data Warehouse maintains a very large database of enrollment records for U.S. commercial health insurers, as well as medical and pharmacy claims related to those clients.

A team of Mayo Clinic researchers accessed that database to examine a nationwide cohort of children born from 2006 through 2012, and who had continuous insurance coverage for at least four years from birth. In the analysis of psychiatric comorbidities and ADHD treatment in the first year after initial diagnosis, only children with at least a year of insurance coverage beyond the ADHD diagnosis were included.

The resulting cohort comprised almost a quarter-million (238,011) children, 49% of whom were girls. The racial/ethnic composition was 72.7% White, 9.8% Hispanic, 6.7% Asian, 6.2% Black, and 4.6% other or unknown.

About 5% of the children who had a diagnosis of ADHD have been made by pediatricians, with the remainder primarily by psychologists, family practice providers, psychiatrists, and neurologists. ADHD diagnoses conformed to standards set in the ninth or tenth revisions of the International Classification of Diseases (ICD-9, ICD-10).

Rates of diagnosis in the U.S. Midwest and West significantly trailed rates in the Northeast and South. Rates also rose steadily with lower household incomes, with children in households with under $40,000 annual incomes being 57% more likely to be diagnosed with ADHD than those with household incomes over $200,000.

After adjusting for sex, region, and household income, Black children were 17% less likely to be diagnosed with ADHD, relative to White children. Hispanic children were 23% less likely to be diagnosed, other/unknown children 27% less likely, and Asian children a staggering 52% less likely.

Both before and after diagnosis of ADHD, Asian children were between two and three times as likely as any other children to be diagnosed with an autism spectrum disorder. White children were more likely to be diagnosed with anxiety disorders. There were no significant differences in the frequency of depressive disorders, disruptive disorders, or oppositional defiant disorder.

After adjusting for sex, census region, and annual household income, White children were also significantly more likely to receive treatment within the first year following diagnosis of ADHD. Black children were 21% less likely to receive treatment, other/unknown children 31% less likely, and Hispanic and Asian children just over half as likely.

The authors noted, “The cause of the disparities in ADHD diagnosis according to race and ethnicity is not fully understood.” They thought it “likely that patients’ concerns about racism play some role in influencing their willingness to approach the healthcare system.” Furthermore, “Health care professionals may also contribute to the racial disparities in diagnosis and treatment. Stereotypes and bias, both explicit and implicit, have been increasingly recognized as factors potentially contributing to physicians’ clinical decision-making. It is possible, for example, that identical behavior displayed by Black and non-Hispanic White children may be interpreted differently based on race-based expectations for the behavior of children, and thus, behavior that is identified as disordered in White children might be inappropriately interpreted as normal in Black children.”

They concluded, “Future study is needed to elucidate the mechanism behind these disparities. Clinicians should provide racially and culturally sensitive care in the evaluation and treatment of ADHD to ensure all children receive appropriate care.”

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Inhibitory control is an essential cognitive control function whereby the prefrontal cortex blocks planned motor actions or interrupts motor actions already initiated by other parts of the brain. For example, someone might instinctually reach for a candy bar but then put it back upon thinking that eating it would conflict with a higher-level goal of cutting down on sugar consumption. Impairment of inhibitory control is a known characteristic of several psychiatric disorders, including ADHD.

Any generally safe treatment with the ability to at least partially reverse such impairment would therefore be useful. Researchers are currently experimenting with transcranial direct current stimulation, a non-invasive brain stimulation technique that uses a weak electrical current to stimulate specific regions of the brain.

What, then, do we know so far about its potential effectiveness for improving inhibitory control?

A team of experts at the University of Tübingen in Germany conducted a comprehensive search of the peer-reviewed medical literature to find out. They then performed a meta-analysis of 45 studies with a combined total of over 1,600 participants. All but four of the studies used sham or other active controls.

The overall meta-analysis found a significant but small improvement in response inhibition. But it also found evidence of publication bias. Adjusting for publication bias reduced the effect size in half, to a tiny but still significant improvement.

The meta-analysis relied on two behavioral tasks that require inhibitory control to measure response inhibition: the go-/no-task, and the stop-signal task. Separating these, there was no significant improvement in the go/no-go task performance. All the improvement was concentrated on the stop-signal task.

The authors noted, “A potential limitation of this meta-analysis is that we could not exhaustively model-dependent relationships between moderator variables (e.g., tDCS polarity and electrode placement),” and “Further high-quality studies are needed to investigate potential interactions between technical and functional parameters in tDCS research.”

Noting that to date, no study investigated potential behavioral and neural markers in adults with subthreshold ADHD as compared to adults with full syndrome ADHD and healthy controls, the Garmin team of researchers at the University of Tübingen out to do just that, recruiting volunteers through flyers and advertisements.

Their ADHD sample consisted of113 adults between 18 and 60 years of age (mean age 38) who fulfilled the DSM-IV-TR criteria of ADHD and were either not on medication or a steady dose of medication over the prior two months.

Another 46 participants (also mean age 38), whose symptoms did not reach the DSM-IV-TR criteria, were assigned to the group with subthreshold ADHD.

The control sample was comprised of 42 healthy participants (mean age 37).

Individuals with schizophrenia, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury were excluded from the sample, as were those with current substance abuse or dependence.

All participants were German-speaking Caucasians. There were no significant differences in gender, age, education, or verbal/nonverbal intelligence among the three groups.

Participants first completed an online pre-screening, which was followed up with an interview to confirm the ADHD diagnosis.

ADHD impairs executive functions, “defined as the ‘top-down’ cognitive abilities for maintaining problem-solving skills to achieve future goals.” The researchers explored three categories of executive functioning: 1) capacity for inhibition, “the ability to inhibit dominant, automatic, or prepotent responses when necessary”; 2) ability to shift, enabling smooth switching between tasks or mental sets; and 3) ability to update, “updating and monitoring of working memory representations.” Participants took a battery of neuropsychological tests to assess performance in each category.

Significant differences emerged between the group with ADHD and healthy controls in all measures except one: the STROOP Reading test. But there were no significant differences between participants suffering from subthreshold and full-syndrome ADHD. Nor were there any significant differences between those with subthreshold ADHD and healthy controls.

The researchers also recorded electroencephalograms(EEGs) for each participant. In healthy individuals, there is little to no association between resting-state EEG spectral power measures and executive functions. In individuals with ADHD, some studies have indicated increased theta-to-beta ratios, while others have found no significant differences. This study found no significant differences between the three groups.

The authors concluded, “The main results of the study can be summarized as follows: First, increased executive function deficits (in updating, inhibition, and shifting functions) could be observed in the full syndrome ADHD as compared to the healthy control group while, on the electrophysiological level, no differences in the theta to the beta ratio between these groups were found. Second, we observed only slightly impaired neuropsychological functions and no abnormal electrophysiological activity in the subthreshold ADHD sample. Taken together, our data suggest some practical uses of the assessment of objective cognitive markers but no additional value of examining electrophysiological characteristics in the diagnosis of subthreshold and full syndrome ADHD in adulthood.”

They added, “These findings deeply question the value of including resting EEG markers into the diagnostic procedure and also have implications for standard neurofeedback protocols frequently used in the treatment of ADHD, where patients are trained to reduce their theta power while simultaneously increasing beta activity.”