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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 German team of researchers at the University of Tübingen out to do just that, recruiting volunteers through flyers and advertisements.

Their ADHD sample consisted of 113 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."

Cortisol is a steroid hormone produced by the adrenal glands situated above the kidneys. Its release is boosted by low blood sugar, which it counteracts, and also in response to stress.

Previous studies on children with ADHD have pointed to lower basal cortisol concentrations in the morning and a significantly lower incidence of typical diurnal fluctuation in cortisol levels.

To better assess the comorbidity of ADHD and adrenal gland disorders, a Taiwan research team affiliated with Chang Gung University College of Medicine used the National Health Insurance database to conduct a nationwide population study. Taiwan has a single-payer national health insurance system that encompasses almost the entire population, and its extensive database facilitates such studies.

Looking at the thirteen years from 1999 through 2011, the team identified 75,247 youths (manage ten years) newly diagnosed with ADHD and matched them by age and sex to another 75, 247 youths not diagnosed with ADHD.

To guard against confounding variables, they also identified psychiatric conditions that are comorbid with ADHD, including oppositional defiant disorder, conduct disorder, autism spectrum disorder, tic disorder, and intellectual disability.

After adjusting for age, sex, and psychiatric comorbidities, youths with ADHD were still 2.4 times more likely to have adrenal gland abnormalities than their normally developing peers. To place this in context, adrenal gland dysfunctions are very uncommon, in this instance occurring in roughly one in a thousand controls, and two in a thousand youths with ADHD.

The team also explored whether the two ADHD medications approved for use in Taiwan had any effect on the outcome. Methylphenidate, a stimulant, is the preferred treatment, with atomoxetine, a non-stimulant, used as an alternative where methylphenidate is inadvisable or found to be suboptimal. Neither methylphenidate nor atomoxetine had any significant effect on the risk of adrenal gland dysfunction.

The authors concluded, "Patients with ADHD had greater comorbid rates with adrenal gland dysfunction than the control subjects. Nevertheless, receiving pharmacotherapy (MPH or ATX) did not significantly influence the risk of developing adrenal gland dysfunction among ADHD patients. Therefore, continuous efforts are needed to promote public awareness of potential adrenal gland dysfunction among ADHD patients."

A German team of researchers performed a comprehensive search of the medical literature and identified 35randomized controlled trials (RCTs) published in English that explored this question. Participating children were between three and six years old. Children with intellectual disabilities, sensory disabilities, or specific neurological disorders such as epilepsy were excluded.

The total number of participating preschoolers was over three thousand, drawn almost exclusively from the general population, meaning these studies were not specifically evaluating effects on children with ADHD. But given that ADHD results in poorer executive functioning, evidence of the effectiveness of cognitive training would suggest it could help partially reverse such deficits.

RCTs assign participants randomly to a treatment group and a group not receiving treatment but often receiving a placebo. But RCTs themselves vary in risk of bias, depending on:

• whether the control condition was passive (i.e. waiting list or no treatment) or active/sham (an activity of similar duration and intensity to the treatment condition)
• whether the outcome was measured by subjective rating (e.g. by questionnaires, susceptible to reporting biases) or more objective neuropsychological testing;
• whether the assessment of outcome was by blinded assessors unaware of participants' treatment conditions;
• whether there was a risk of bias from participants dropping out of the trial.

After evaluating the RCTs by these criteria, the team performed a series of meta-analyses.

Combining the 23 RCTs with over 2,000 children that measured working memory, they found that cognitive training led to robust moderate improvements. Looking only at the eleven most rigorously controlled studies strengthened the effect, with moderate-to-large gains.

Twenty-six RCTs with over 2,200 children assessed inhibitory control. When pooled, they indicated a small-to-moderate improvement from cognitive training. Including only the seven most rigorously controlled studies again strengthened the effect, boosting it into the moderate effect zone.

Twelve RCTs with over 1,500 participants tested the effects of cognitive training on flexibility. When combined, they pointed to moderate gains. Looking at only the four well-controlled studies boosted the effect to strong gains. Yet here there was evidence of publication bias, so no firm conclusion can be drawn.

Only four studies with a combined total of 119 preschoolers tested the effects on ADHD ratings. The meta-analysis found a small but non-significant improvement, very likely due to insufficient sampling. As the authors noted, "some findings of the meta-analysis are limited by the insufficient number of eligible studies. Specifically, more studies are needed which use blinded assessments of subjective ratings of ADHD ... symptoms ..."

The authors concluded that their meta-analyses revealed significant, mostly medium-sized effects of the preschool interventions on core EFs [executive functions] in studies showing the low risk of bias."

Certain air pollutants can produce free radicals and inflammatory cytokines that can penetrate the central nervous system and affect behavior. Long-term exposure to air pollution has been associated with a higher risk of developing ADHD.

There has, however, been little focus on the short-term effects of exposure. Might there be any correlation between levels of air contaminants and subsequent healthcare visits of adolescents for severe spikes in ADHD symptoms (frequently but not always associated with comorbid conduct disorder, oppositional defiance disorder, or mood disorder), such as extreme hyperactivity, serious rule violations, theft, or aggression to people or animals?

A South Korean (Republic of Korea) research team explored this question through a nationwide cohort study using the database of the National Health Insurance Service, a single-payer system, that covers the entire population.

Using a time-series approach, they compared measured levels of three airborne pollutants - particulate matter with a diameter ≤ 10 μm (PM10), nitrogen oxide (NO2), produced by vehicular traffic, and sulfur dioxide (SO2), produced by manufacturing industries- with healthcare visits with a principal diagnosis of ADHD. They chose these three contaminants because they have been associated with ADHD in long-term studies. What made this approach feasible is that healthcare visits are typically unscheduled in Korea, making it possible to get quick medical attention.

The team divided the country into sixteen regions, looked at boys and girls separately, and also split adolescents into two age groups (10 to 14 years and 15 to 19 years). They estimated region-specific daily concentrations of the three pollutants from 318 government-run monitoring sites, located according to population density and distribution.

The researchers next calculated zero(same day) to five-day lag figures for ADHD-related healthcare visits in each region and ran meta-analyses on the time-series data.

There were 7,200 ADHD-related healthcare visits in the 2013-2015 study period. Major increases in PM10 levels were associated with increased ADHD-related healthcare visits from the day of the spike to three days later, peaking the day after the upturn. Major increases in SO2 levels were associated with increased ADHD-related healthcare visits from one to four days later, peaking the day following the upturn. Major increases in NO2 levels were associated with increased ADHD-related healthcare visits from one to four days later, peaking three days after the spike.

There were no significant differences between male and female adolescents, and between younger and older adolescents.

The strongest increased risk for ADHD-related healthcare visits was for NO2 spikes (up 47 percent), followed by SO2 spikes (up 27 percent), with PM10 spikes coming in last (up 12 percent).

Among the limitations, the authors were unable to evaluate the most hazardous types of particulate emissions, because the smaller-diameter PM2.5 particles (≤2.5 μm) have only been measured partially in South Korea since 2015. On the other hand, they pointed out that this was the first study to investigate associations between short-term air pollution exposure and ADHD-related healthcare visits, and that it included all ADHD-related healthcare visits in South Korea, making the possibility of selection bias negligible. They recommended conducting similar studies on other national populations.

There is strong evidence of the effectiveness of a variety of ADHD medicines in reducing ADHD symptoms. While some are more effective than others, another factor in deciding on a course of treatment is minimizing noxious side effects.

One of those side effects is a headache.

An international team of researchers from Sweden, Germany, the Netherlands, the United Kingdom, the United States, and Australia conducted a systematic review of the peer-reviewed medical literature about ADHD and headaches on the one hand, and ADHD medications and headaches on the other.

As a baseline, they performed a meta-analysis of twelve studies with a combined total of over 2.7 million participants that compared headache rates between youths with and without ADHD. Those with ADHD were twice as likely to suffer from headaches. This held even after limiting the meta-analysis to the four studies that adjusted for confounders.

Breaking down the results by type of headache revealed a fascinating distinction. There was no significant difference in rates of tension headaches, but migraines were 2.2 times as frequent among youths with ADHD.

This strong association between ADHD and migraines suggests looking for medications that are both effective and unlikely to further contribute to the odds of migraine.

Accordingly, the team examined associations between specific ADHD medications and headaches.

Stimulant medications are generally considered the most effective medications for treating ADHD. A meta-analysis of ten studies with 2,672 participants found no association between amphetamines and headaches. On the other hand, a meta-analysis of 17 studies with 3,371 participants found that methylphenidate increased the odds of headache by one-third (33%).

The non-stimulant atomoxetine is usually considered a second-tier treatment for those among whom stimulants are contraindicated. A meta-analysis of 22 studies encompassing 3,857 participants found it increased the odds of headache by 29%.

Guanfacine fared worst of the bunch. A meta-analysis of eight studies combining 1,956 participants found it increased the odds of headache by 43%.

Finally, a meta-analysis of six studies with a combined total of 818 participants found no association with headaches.

There was no indication of publication bias in any of the meta-analyses.