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August 1, 2021
The ENIGMA-ADHD Working Group published a second large study on the brains of people with ADHD in the American Journal of Psychiatry this month. In this second study, the focus was on the cerebral cortex, which is the outer layer of the brain.
ADHD symptoms include inattention and/or hyperactivity and acting impulsively. The disorder affects more than one in twenty (5.3%) children, and two-thirds of those diagnosed continue to experience symptoms as adults.
In this study, researchers found subtle differences in the brain's cortex when they combined brain imaging data on almost 4,000 participants from 37 research groups worldwide. The differences were only significant for children and did not hold for adolescents or adults. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found in the thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.
These subtle differences in the brain's cortex were not limited to people with the clinical diagnosis of ADHD: they were also present - in a less marked form - in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation Study from Rotterdam, which has brain images of, 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. Furthermore, siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.
This is the largest study to date to look at the cortex of people with ADHD. It included 2246 people with a diagnosis of ADHD and 1713 people without, aged between 4 and 63 years old. This is the second study published by the ENIGMA-ADHD Working Group; the first examined structures that are deep in the brain. The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations.
The authors say the findings could help improve understanding of the disorder. 'We identify cortical differences that are consistently associated with ADHD, by combining data from many research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioral and genetic studies.'. In the future, the ADHD Working Group hopes to look at additional key features in the brain - such as the structural connections between brain areas - and to increase the representation of adults affected by ADHD, on whom limited research has been performed to date.
Many news outlets have reported an increase – or surge – in attention-deficit/hyperactivity disorder, or ADHD, diagnoses in both children and adults. At the same time, health care providers, teachers and school systems have reported an uptick in requests for ADHD assessments.
These reports have led some experts and parents to wonder whether ADHD is being overdiagnosed and overtreated.
As researchers who have spent our careers studying neurodevelopmental disorders like ADHD, we are concerned that fears about widespread overdiagnosis are misplaced, perhaps based on a fundamental misunderstanding of the condition.
Discussions about overdiagnosis of ADHD imply that you either have it or you don’t.
However, when epidemiologists ask people in the general population about their symptoms of ADHD, some have a few symptoms, some have a moderate level, and a few have lots of symptoms. But there is no clear dividing line between those who are diagnosed with ADHD and those who are not, since ADHD – much like blood pressure – occurs on a spectrum.
Treating mild ADHD is similar to treating mild high blood pressure – it depends on the situation. Care can be helpful when a doctor considers the details of a person’s daily life and how much the symptoms are affecting them.
Not only can ADHD symptoms be very different from person to person, but research shows that ADHD symptoms can change within an individual. For example, symptoms become more severe when the challenges of life increase.
ADHD symptoms fluctuate depending on many factors, including whether the person is at school or home, whether they have had enough sleep, if they are under a great deal of stress or if they are taking medications or other substances. Someone who has mild ADHD may not experience many symptoms while they are on vacation and well rested, for example, but they may have impairing symptoms if they have a demanding job or school schedule and have not gotten enough sleep. These people may need treatment for ADHD in certain situations but may do just fine without treatment in other situations.
This is similar to what is seen in conditions like high blood pressure, which can change from day to day or from month to month, depending on a person’s diet, stress level and many other factors.
ADHD symptoms start in early childhood and typically are at their worst in mid-to late childhood. Thus, the average age of diagnosis is between 9 and 12 years old. This age is also the time when children are transitioning from elementary school to middle school and may also be experiencing changes in their environment that make their symptoms worse.
Classes can be more challenging beginning around fifth grade than in earlier grades. In addition, the transition to middle school typically means that children move from having all their subjects taught by one teacher in a single classroom to having to change classrooms with a different teacher for each class. These changes can exacerbate symptoms that were previously well-controlled. Symptoms can also wax and wane throughout life.
Psychiatric problems that often co-occur with ADHD, such as anxiety or depression, can worsen ADHD symptoms that are already present. These conditions can also mimic ADHD symptoms, making it difficult to know which to treat. High levels of stress leading to poorer sleep, and increased demands at work or school, can also exacerbate or cause ADHD-like symptoms.
Finally, the use of some substances, such as marijuana or sedatives, can worsen, or even cause, ADHD symptoms. In addition to making symptoms worse in someone who already has an ADHD diagnosis, these factors can also push someone who has mild symptoms into full-blown ADHD, at least for a short time.
The reverse is also true: Symptoms of ADHD can be minimized or reversed in people who do not meet full diagnostic criteria once the external cause is removed.
Clinicians diagnose ADHD based on symptoms of inattention, hyperactivity and impulsivity. To make an ADHD diagnosis in children, six or more symptoms in at least one of these three categories must be present. For adults, five or more symptoms are required, but they must begin in childhood. For all ages, the symptoms must cause serious problems in at least two areas of life, such as home, school or work.
Current estimates show that the strict prevalence of ADHD is about 5% in children. In young adults, the figure drops to 3%, and it is less than 1% after age 60. Researchers use the term “strict prevalence” to mean the percentage of people who meet all of the criteria for ADHD based on epidemiological studies. It is an important number because it provides clinicians and scientists with an estimate on how many people are expected to have ADHD in a given group of people.
In contrast, the “diagnosed prevalence” is the percentage of people who have been diagnosed with ADHD based on real-world assessments by health care professionals. The diagnosed prevalence in the U.S. and Canada ranges from 7.5% to 11.1% in children under age 18. These rates are quite a bit higher than the strict prevalence of 5%.
Some researchers claim that the difference between the diagnosed prevalence and the strict prevalence means that ADHD is overdiagnosed.
We disagree. In clinical practice, the diagnostic rules allow a patient to be diagnosed with ADHD if they have most of the symptoms that cause distress, impairment or both, even when they don’t meet the full criteria. And much evidence shows that increases in the diagnostic prevalence can be attributed to diagnosing milder cases that may have been missed previously. The validity of these mild diagnoses is well-documented.
Consider children who have five inattentive symptoms and five hyperactive-impulsive symptoms. These children would not meet strict diagnostic criteria for ADHD even though they clearly have a lot of ADHD symptoms. But in clinical practice, these children would be diagnosed with ADHD if they had marked distress, disability or both because of their symptoms – in other words, if the symptoms were interfering substantially with their everyday lives.
So it makes sense that the diagnosed prevalence of ADHD is substantially higher than the strict prevalence.
People who are concerned about overdiagnosis commonly worry that people are taking medications they don’t need or that they are diverting resources away from those who need it more. Other concerns are that people may experience side effects from the medications, or that they may be stigmatized by a diagnosis.
Those concerns are important. However, there is strong evidence that underdiagnosis and undertreatment of ADHD lead to serious negative outcomes in school, work, mental health and quality of life.
In other words, the risks of not treating ADHD are well-established. In contrast, the potential harms of overdiagnosis remain largely unproven.
It is important to consider how to manage the growing number of milder cases, however. Research suggests that children and adults with less severe ADHD symptoms may benefit less from medication than those with more severe symptoms.
This raises an important question: How much benefit is enough to justify treatment? These are decisions best made in conversations between clinicians, patients and caregivers.
Because ADHD symptoms can shift with age, stress, environment and other life circumstances, treatment needs to be flexible. For some, simple adjustments like classroom seating changes, better sleep or reduced stress may be enough. For others, medication, behavior therapy, or a combination of these interventions may be necessary. The key is a personalized approach that adapts as patients’ needs evolve over time.
Executive function impairment is a key feature of ADHD, with its severity linked to the intensity of ADHD symptoms. Executive function involves managing complex cognitive tasks for organized behavior and includes three main areas: inhibitory control (suppressing impulsive actions), working memory (holding information briefly), and cognitive flexibility (switching between different mental tasks). Improving executive functions is a critical objective in the management of ADHD.
Recent studies show that exercise interventions can enhance executive function in individuals with ADHD. Unlike traditional medications, which are costly and may cause side effects such as headaches, nausea, or growth issues, exercise can be incorporated into daily routines of children and adolescents without negative reactions.
Some studies report that aerobic exercise does not significantly improve executive function. However, most past reviews of aerobic exercise effects on executive function have focused on people without ADHD, with few examining interventions for children or adolescents with ADHD.
The Study:
A Chinese and South Korean study team conducted a systematic search of the peer-reviewed published literature to perform meta-analyses on randomized controlled trials (RCTs) specifically focused on aerobic exercise interventions for children and adolescents with ADHD.
All studies included were randomized controlled trials involving participants aged 6 to 18 years who had been clinically diagnosed with ADHD. The interventions consisted of various forms of aerobic exercise, while the control groups engaged in either non-exercise activities or daily routines. Each study was required to report at least one outcome measure with usable data for calculating the effect size on executive functioning.
The Results:
Meta-analysis of fifteen RCTs combining 653 children and adolescents with ADHD reported a medium to large effect size improvement in inhibitory control. There was no sign of publication bias, but wide heterogeneity (variation) in outcomes among studies.
Six to eight weeks of aerobic exercise produced modest improvements, with much greater gains seen after twelve weeks. Hour-long sessions were as effective as longer ones. Moderate intensity exercise proved more beneficial than vigorous intensity.
Meta-analysis of eight RCTs combining 399 children and adolescents with ADHD produced a medium effect size improvement in working memory. There was no sign of publication bias, and heterogeneity was moderate.
Once again, six to eight weeks of aerobic exercise produced modest improvements, with much greater gains seen after twelve weeks. Hour-long sessions were as effective as longer ones. But in this case moderate-to-vigorous intensity yielded the best results.
Meta-analysis of ten RCTs combining 443 children and adolescents with ADHD was associated with a medium to large effect size improvement in cognitive flexibility. There was no sign of either publication bias or heterogeneity. Neither the length of treatment, session time, or intensity affected the outcome.
The Take-Away:
The team concluded, “Our study indicates that aerobic exercise interventions have a positive impact with a moderate effect size on inhibitory control, working memory, and cognitive flexibility in children and adolescents with ADHD. However, the effectiveness of the intervention is influenced by factors such as the intervention period, frequency, session durations, intensity, and the choice between acute or chronic exercise. Specifically, chronic aerobic exercise interventions lasting 12 weeks or longer, with a frequency of 3 to 5 sessions per week, session durations of 60 min or more, and intensities that are moderate or moderate-to-vigorous, have the greatest overall effect… caution should be exercised when interpreting these findings due to the significant heterogeneity in inhibitory control and working memory.”
Vitamins play important roles in metabolism, immune regulation, and neurodevelopment. Recent studies show that deficiencies in vitamins like D, B6, B12, and folate are common in people with ADHD and ASD (autism spectrum disorder), and are associated with behavioral, cognitive, and brain development issues.
The Study:
A study team based in China has just performed a systematic search of the peer-reviewed medical literature to perform meta-analyses of clinical trials exploring vitamin interventions in the treatment of ADHD and ASD.
ADHD trials included participants with an official diagnosis. The primary intervention was vitamin supplements, while other treatments, including medications, remained unchanged or were excluded during the study period. ADHD outcomes included measurable changes in ADHD symptoms using validated rating scales and executive function measures.
Eligible studies included standard or sham control groups, crossover, parallel, or other clinical trial designs. In crossover studies, only first-phase data were analyzed to prevent carryover effects.
Ten trials with 852 participants met the standards, but meta-analysis showed no significant results. The outcomes varied widely, suggesting a need to distinguish among vitamins.
Results:
Of the five trials involving 347 participants that specifically evaluated vitamin D supplementation, results indicated a large effect size improvement in ADHD symptoms and executive function measures. The other five studies did not show any observable improvement.
Key limitations include:
The team concluded, “This meta-analysis supports the use of vitamin supplementation as a promising adjunctive treatment for ASD and ADHD. Vitamin B showed greater benefits in improving symptoms of ASD, while vitamin D was more effective in managing ADHD-related behaviors. These findings suggest that specific vitamins may target disorder-specific symptoms. Despite limitations such as the lack of trials on other vitamins and limited understanding of underlying mechanisms, vitamin therapy remains a low-cost, accessible option.”
An important limitation of this work is that the positive results for vitamin D were due to two studies from Iran. So far, no positive study has emerged from a non-Iranian study.
Interpretation:
The vitamin D findings are intriguing and could be important if replicated outside of Iran. Since supplementation is already widely recommended to those with limited sunlight exposure, clinicians may want to consider monitoring their patients’ vitamin D intake, especially in the winter months. It should be noted, however, that due to the limitations of this study, the results are by no means conclusive, and vitamin D should not be taken as a stand-alone treatment for ADHD.
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