What would you like to find today?

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.

What relationship, if any, might there be between childhood ADHD and subsequent psychotic disorders? Previous epidemiological studies have produced conflicting results.

‍
A French team of physicians conducted a systematic search of the peer-reviewed literature to conduct a meta-analysis to examine this question in greater depth.
They pooled twelve studies with a combined total of 1.85 million participants, consisting of 124,095 with ADHD and just over 1.72 million controls.

The psychotic disorders analyzed included schizophrenia, schizophreniform disorder, schizotypal personality disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, and psychotic disorder not otherwise specified. These disorders had to be diagnosed after the diagnosis of ADHD in children and adolescents under 18 years old.

The meta-analysis found that persons diagnosed in childhood or adolescence with ADHD were well over four times more likely to have subsequent diagnoses of psychotic disorders than those without a diagnosis of ADHD. Limiting the meta-analysis to the six studies that were adjusted for confounders produced an identical result.

There were no statistically significant between-group differences for subgroup analyses comparing psychotic disorder or schizophrenia outcomes, cohort or case-control study design, and adjusted or unadjusted estimates. There were no significant differences between males and females.

Heterogeneity among studies was moderate (43%), and there was no sign of publication bias. Removing one study reduced heterogeneity to low levels (18%), while very slightly raising the odds of subsequent diagnosis of psychotic disorder. Looking only at the more restrictive diagnosis of schizophrenia also made no difference in the odds.

No matter how the data were analyzed, in all instances, the odds of subsequent diagnosis of psychotic disorder rose well over fourfold for those diagnosed with ADHD in their youth.

The authors concluded, "To improve our knowledge, further cohort studies should be conducted. Ideally, these studies would ensure a sufficiently long follow-up to account for the mean age at which P [psychotic disorders] develop. Such studies should consider the use of psychostimulants and the role of SUD [substance use disorder] in the causal path between ADHD and PD."

In the five years from 2006 through 2010, the child falls led to 11,535 head injuries in the United States, costing a billion dollars to treat. Previous studies have shown that persons with ADHD were more prone to accidental falls than normally developing individuals. Just how strong is that association among American youth?

A team of Stanford University researchers examined data for falls among youths under 18 years old from the Nationwide Emergency Department Sample (NEDS), covering 953 hospitals in 36 states between 2010 and 2015. These included falls from stairs, ladders, or scaffolding; falls from buildings or other structures; falls into holes; other falls from one level to another; falls on the same level from collisions, pushing, shoving, slipping, tripping, or stumbling.

Out of almost 49 million injuries involving youths recorded by hospital emergency departments in the NEDS from 2010 to 2015, there were 13,217,237 million falls, 139,642 of which involved youths 5-17 years old with ADHD only. These were compared with almost 7.8 million involving youths 5-17 years old with developmental disabilities.

The team adjusted for the following covariates to reduce confounding: age category, sex, income, payment source, developmental disability status, and mechanism of fall.

Youths with ADHD were found to be roughly 75% more likely than normally developing youths to be admitted for unintentional falls in hospital emergency departments. They were about 60% more likely to be admitted for hospital stays exceeding two days. They were almost twice as likely to require surgery. And they were four times as likely to require intubation through the mouth and into the airway to be placed on a ventilator to assist with breathing.

These outcomes are not surprising, given that a large proportion of youths with ADHD are prone to be more inattentive and/or impulsive on average than their normally developing peers. But they underscore the need for parents and physicians to take preventive action to reduce the chance of harm.

The authors "suggest that practitioners who provide care for children with ADHD spend extra time on educating parents regarding the increased risk of falls, especially among older children, to decrease the odds of worse outcomes from unintentional falls."

Polycystic ovary syndrome (PCOS) is a disorder affecting women of reproductive age, characterized by elevated levels of male hormones (androgens). The name is derived from the presence of cysts surrounding the ovum, which cause enlargement of the ovaries. Its cause remains unknown. There is speculation that high androgen levels could affect brain development in the fetus.

A team of Iranian researchers (Maleki et al.) published a twofold meta-analysis earlier this year exploring the relationship between PCOS and offspring ADHD. A systematic search of the peer-reviewed medical literature came up with six studies, consisting of three cohort studies, and three case-control studies.

A meta-analysis of the three case-control studies with a combined total of 79,978 participants found that children of mothers with PCOS were 42 percent more likely to develop ADHD.

A separate meta-analysis of the three cohort studies with a combined total of 325,435 participants produced essentially identical outcomes: children of mothers with PCOS were 43 percent more likely to develop ADHD.

There was no indication of publication bias in either meta-analysis and virtually no heterogeneity. Except for one case-control study, all studies were considered to be of high quality.

The authors concluded, "Our study showed that maternal PCOS is a risk factor for ADHD. Therefore, Screening for ADHD among children of these women should be considered as part of the comprehensive clinical care for women with PCOS."

More recently, a second-team (Dubey et al.), based in Texas, published a meta-analysis on the same subject. Their systematic search produced the same studies, but classified one study described as case-control by Malekiet al. as a cohort study.

Their meta-analysis of four cohort studies with a combined total of over two million participants (they counted participants differently than Maleki et al.) found that children of mothers with PCOS were 43 percent more likely to develop ADHD. Adjusting for confounders made no difference.

Again, there was no indication of publication bias, and between-study heterogeneity was virtually nil.

Considering they relied on the same studies, the fact that both teams reported identical outcomes is unsurprising, confirming there's a clear association between maternal PCOS and ADHD in offspring.