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Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition that is typically diagnosed in childhood but can persist into adulthood. Its symptoms include inattention, hyperactivity, and impulsivity, and it can significantly affect daily life, academic achievement, and professional success. As scientific understanding of the condition continues to evolve, new research is revealing more insights into the prevalence, comorbidity, treatment, and physiological aspects of ADHD in adults. Here's a roundup of some recent findings:

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Location of Mental Healthcare and ADHD Treatment Prevalence

A recent study assessing the prevalence of treatment for ADHD among US college students found that the location of mental health care significantly affects treatment outcomes. Specifically, students receiving mental healthcare on campus were less likely to receive any medication or therapy for ADHD, suggesting the need to evaluate the quality of mental health services available on college campuses and their effectiveness in treating ADHD.

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 Oxidative Stress and l-Arginine/Nitric Oxide Pathway in ADHD 

Another study found a correlation between ADHD and the l-Arginine/Nitric oxide (Arg/NO) pathway, a physiological process linked to dopamine release and cardiovascular functioning. The study found that adults with ADHD who were not treated with methylphenidate (a common ADHD medication) showed variations in the Arg/NO pathway. This could have implications for monitoring potential cardiovascular side effects of ADHD medications, as well as for understanding the biochemical changes that occur in ADHD. 

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Chronic Pain in ADHD

ADHD and chronic pain appear to be related, according to a comparative study of clinical and general population samples. Particularly in females with ADHD, the prevalence of chronic and multisite pain was found to be high. This calls for longitudinal studies to understand the complex sex differences of comorbid chronic pain and ADHD in adolescents and the potential impacts of stimulant use on pain.

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ADHD and Violent Behavior

Finally, a study investigated the comorbidity of ADHD and bipolar disorder (BD) and its potential link to violent behavior. The research revealed a positive effect of ADHD symptoms on violence tendency and aggression scores. Moreover, male gender and young age were also found to have significant positive effects on violence and aggression scores, suggesting an association between these disorders and violent behavior.

Noting that the degree of comorbidity (co-occurrence) between epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that. 

Their systematic search of the peer-reviewed medical literature yielded 17 studies examining the prevalence of epilepsy among persons with ADHD, and 49 studies measuring the prevalence of ADHD among persons with epilepsy.

According to the Apple dictionary app, epilepsy is “a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain.” Its lifetime prevalence in the general population is about 0.76%, or about one in every 130 persons.

Meta-analysis of 17 studies with a combined total of over 900,000 participants spread over twelve countries on five continents yielded an epilepsy prevalence estimate of 3.4% among individuals with ADHD, or well over four times the prevalence in the general population. There was no sign of publication bias, but variability (heterogeneity) among studies was extremely high.

The worldwide prevalence of ADHD in children, on the other hand, is about 7.2%, affecting roughly one in fourteen.

Meta-analysis of 49 studies with a combined total of 172,206 persons from 16 countries on five continents reported an ADHD prevalence of just over 22% among persons with epilepsy. However, heterogeneity among studies was extremely high, and there was very strong evidence of publication bias. 

Using the trim-and-fill correction for publication bias yielded a reduced estimate of 16%, which is still over twice the prevalence in the general population.

Furthermore, the authors noted, “Given that the large sample studies in this study are basically population-based studies and the small sample studies are hospital-based studies, there is also the possibility of Berkson’s bias. Specifically, patients with comorbidities are more likely to need help or seek medical advice. This possibility would yield a higher comorbidity rate in hospital-based studies.”

And that is exactly what emerged from subgroup analysis. The prevalence of ADHD in epilepsy among the hospital-based studies was 27.1%, over twice the 13.2% prevalence reported from the 13 population-based studies. The largest population-based study, a U.S. study with over 114,000 participants, yielded a prevalence of only 3.5%.

The authors cautioned that the very high degree of heterogeneity between studies indicates “it is inappropriate to consider the summary effect as representative of the real effect.”

ADHD often includes a problem called disinhibition. This means that the brain struggles to control attention, thoughts, emotions, and behavior, which can lead to negative outcomes. Normally, inhibition helps people stay focused and avoid distractions, but when it fails, it's called disinhibition.

Children with ADHD who have problems with inhibition may face issues like substance abuse, self-harm, and antisocial behavior. Improving their inhibition can help them better manage themselves, do well in school, and have better relationships.

A team of researchers from China and South Korea explored whether physical activity could improve inhibition in children with ADHD. They reviewed studies and excluded those without control groups, those with poor quality assessments, and those involving other interventions like cognitive training or supplements. Their final analysis included 11 studies with 713 participants.

Key Findings on Physical Activity

1. Frequency and Duration: Physical activity had to be done at least twice a week to show significant improvement in inhibition. Sessions needed to last between 45 minutes to an hour for noticeable benefits, with sessions over an hour showing even greater improvements.
2. Consistency: Regular, long-term physical activity was more effective than single sessions.
3. Intensity: Moderate-to-vigorous activities were better than moderate activities alone.
4. Type of Activity:some text
   • Open-skilled sports (like ping-pong or taekwondo) which involve reacting to changing environments, showed the most significant improvements.
   • Closed-skill sports (like running or swimming) showed smaller improvements.
   • Exergaming (exercise using video games) had moderate benefits.
5. Specific Improvements:some text
   • Improvements in response inhibition (the ability to control impulsive responses) were small to medium.
   • Improvements in interference suppression (preventing distractions from affecting working memory) were large.

Conclusion

The research concluded that physical activity can significantly improve the inhibition in children with ADHD, especially with regular, moderate-to-vigorous, open-skilled exercise done at least twice a week for an hour or more. Future studies should continue to explore this with high-quality methods to confirm these findings.

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Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.

CCT programs target one or more cognitive processes such as motor inhibition, interference inhibition, sustained attention, and working memory. They ramp up task difficulty as performance improves. The goal is to harness the brain’s inherent adaptability (neuroplasticity) to boost performance. 

A European study team that previously probed the efficacy of CCT through meta-analysis had been unable to provide a robust estimate of effect size due to an insufficient number of high-quality trials with probably blinded outcomes. Noting that “there have been a considerable number of new RCTs [randomized controlled trials] published, many with larger samples, well-controlled designs and blinded outcomes,” the team performed an updated systematic review and meta-analysis.

They included RCTs with participants of any age who either had a clinical diagnosis of ADHD or were above cut-off on validated ADHD rating scales. RCTs had to have been peer-reviewed and published in an academic journal, and to have reported a validated outcome measure of ADHD symptoms, neuropsychological processes, and/or academic outcomes.

Fourteen RCTs with a combined total of 631 participants had probably blinded outcomes. Meta-analysis of these studies yielded no significant effect on either overall ADHD symptoms or hyperactivity/impulsivity symptoms. There was a marginally significant reduction in inattention symptoms, but the effect size was small. Between-study variation (heterogeneity) was negligible and there was no sign of publication bias.

Regarding academic outcomes, meta-analyses revealed no gain in arithmetic ability or reading fluency. There was a small but not statistically significant improvement in reading comprehension. Heterogeneity was minimal, with no indication of publication bias.

With two related exceptions, meta-analyses of RCTs measuring executive functions likewise reported no significant improvements in attention, interference inhibition (initial stage in controlling impulsive behavior), motor inhibition (follow-up stage in controlling impulsive behavior), non-verbal reasoning, processing speed, and set shifting (the ability to unconsciously shift attention between one task and another).

The exceptions were for working memory tasks. Meta-analysis of 15 RCTs with a combined 753 participants reported a highly significant small-to-medium effect size improvement in verbal working memory. A separate meta-analysis of nine RCTs with a total of 441 participants similarly reported a highly significant improvement in visuospatial working memory, this time with medium effect size.

The team concluded, “There was no empirical support for the use of CCT as a stand-alone intervention for ADHD symptoms based on the largest and most comprehensive meta-analysis of RCTs conducted to date. Small effects, of likely limited clinical importance, on inattention symptoms were found – but these were limited to the setting in which the intervention was delivered. Robust evidence of small- to-moderate improvements in visual-spatial and verbal STM/WM tasks did not transfer to other domains of executive functions or academic outcomes.”

Norway has a single-payer health insurance system that covers virtually the entire population and is linked to a series of national registries tracking all sorts of data including criminal records.

Using this data, a study team identified all 5,624 persons aged 10 to 18 diagnosed with ADHD between 2009 and 2011. It tracked their use of ADHD medication, and subsequent criminal charges. 

Filled prescriptions were primarily for stimulant methylphenidate (90%) and the nonstimulant atomoxetine (9.5%). They tracked the cumulative number of daily defined doses (DDD) filled for any ADHD prescriptions following ADHD diagnosis. 

They also compared this group with a general population sample of persons aged 10 to 18 without contact with mental health services, matched on age, sex, and geography.

They adjusted for the following confounders: age, sex, year of contact with clinic, psychiatric comorbidity at time of diagnosis, country of birth, charges before ADHD diagnosis, parents’ marital status, parent’s highest education when the child was 6 years, and parent’s labor income when the child was 6 years. 

They further adjusted for municipality-level population size and high school dropout rates, and the following aggregated measures from the random sample of the general population: municipality-level labor income of parents and clinic-level percent of youth crime, youth immigrants, mothers’ marriage rate, and parents’ education level.

Comparing persons with ADHD to the matched general population over eight years follow-up, those with ADHD had considerably higher rates of criminal charges:

• 2.7 times more likely to be charged with any crime.
• 6 times more likely to be charged with a violent crime.
• 7 times more likely to be charged with a sexual offense (though only among males)
• 4 times more likely to be charged with property crimes.

Next the team examined outcomes of pharmaceutical treatment.

Comparing persons with ADHD undergoing pharmacological treatment with those not receiving such treatment, those undergoing treatment had lower rates of certain criminal charges. At two years follow-up, those treated had 7.3% less violence-related charges. This corresponds to a number needed to treat (NNT) estimate of 14, indicating that on average treating 14 patients for two years avoids one violence-related criminal charge. Pharmacological treatment reduces public-order charges by at four years follow-up by 15.4% (NNT = 7), and any crime at three years follow-up by 18.5% (NNT = 5).

The authors noted, “Violence and public-order crimes are often caused by reactive-impulsive behavior which is more common in ADHD,” and concluded, “this is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment, while no effects were found in crimes requiring criminal intent, conspiracy, and planning.”

Perfluoroalkylated substances (PFASs), commonly known as "forever chemicals" in the media, are pollutants that do not break down in the environment. Their chemical structure includes fluorine atoms bonded to carbon, which makes them effective at repelling water. This property has led to their use in water-repellent clothing, stain-resistant carpets and furniture, and nonstick cookware.

However, the same chemical structure that makes PFASs useful also makes them a concern for human and animal health, as there are no natural biological processes to remove them from the body. Once ingested, they accumulate and become more concentrated at each level of the food chain. PFASs can also cross the placental barrier, raising concerns about potential harm to developing embryos and fetuses.

A Chinese research team conducted a systematic review of the medical literature to examine if there is a link between maternal exposure to PFASs and an increased risk of ADHD in children. They analyzed data from several studies:

- A meta-analysis of five studies involving 2,513 mother-child pairs found no increase in ADHD risk from exposure to PFOA (perfluorooctanoate) or PFOS (perfluorooctane sulfonate). The consistency across these studies was high, with little variation and no evidence of publication bias.

- Another meta-analysis of three studies with 995 mother-child pairs also showed no increase in ADHD risk from exposure to PFNA (perfluorononanoate) or PFHxS (perfluorohexane sulfonate), with similarly negligible variation between studies and no publication bias.

- In an analysis comparing the highest and lowest quartiles of maternal exposure, a slight increase in ADHD risk was observed with PFOA exposure, while a slight decrease was noted with PFOS exposure. Both findings were marginally significant and may be due to the small sample sizes. 

The researchers concluded that more studies are needed to confirm these findings due to the limited evidence available.

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Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be sub-optimal in ADHD.

Most treatment guidelines recommend stimulants as the preferred treatment for ADHD, because they respond faster, and studies show they have higher efficacy in reducing symptoms. But for individuals for whom treatment with stimulants is subpar, guidelines recommend non-stimulants as second-line treatment.

Previous meta-analyses have focused on efficacy among children and adolescents with ADHD. This meta-analysis, by a Chinese study team, expanded its reach to not only update the former, but also include studies of adults.

The team’s systematic search of the medical literature for double-blind randomized controlled trials (RCTs) identified eleven that could be combined for meta-analysis. With only a single study of efficacy for adults, however, no meta-analysis could be performed specific to persons 18 and older.

Meta-analysis of all eleven studies with a combined total of 2,623 participants found guanfacine to be roughly 75% more effective than placebo for reducing ADHD symptoms. Variation between studies (heterogeneity) was low. There was no sign of publication bias.

Breaking that down by length of time on guanfacine found no evidence of a dose-response effect, however. In fact, participants with less than ten weeks of treatment (seven RCTs, 1,771 participants) outperformed those with longer periods of treatment (four RCTs, 852 participants) with a narrow overlap in the 95% confidence limits.

The outcomes were also sensitive to the ADHD symptom scale used. Meta-analysis of RCTs using the Clinical Global Impression of Improvement treatment response score (four studies, 850 participants) reported no significant improvement, while RCTs relying on ADHD-Rating-Scale-IV (six studies, 1,128 participants) reported a significant improvement, but without providing a standardized effect size.

Finally, a meta-analysis of ten RCTs with a combined total of 2,273 persons found a 23% increase in treatment-emergent adverse events for guanfacine relative to placebo. The three most common such events in the guanfacine group were somnolence (38.6%), headache (20.5%), and fatigue (15.2%).

Are attention-deficit/hyperactivity disorder (ADHD) medications associated with risk of cardiovascular disease (CVD)?

An international study team has just explored this question with a meta-analysis of nineteen studies with a total of almost four million participants of all ages. It included 3,931,532 participants from six countries or regions: United States, South Korea, Canada, Denmark, Spain, and Hong Kong. 

Overall, using the entire data set, it found no significant association between any ADHD medication use and any cardiovascular event. 

The same held true when breaking this down by children and adolescents (twelve studies with over 1.7 million participants), young and middle-aged adults (seven studies with over 850,000 participants), and older adults (six studies with over a quarter million participants).

The team then compared the data for stimulant medications with data for non-stimulant medications. A meta-analysis of 17 studies with over 3.8 million participants found no significant association between stimulant medications and cardiovascular risk. Similarly, a meta-analysis of three studies with over 670,000 participants found no significant association between non-stimulant medications and cardiovascular risk.

Distinguishing between types of cardiovascular risk made no difference. For instance, a meta-analysis of nine studies with over 900,000 participants found no effect of stimulant medications on risk of myocardial infarction (heart attack), and a meta-analysis of six studies, also with over 900,000 participants, found no effect of stimulant medications on risk of cerebrovascular disease, including stroke, brain aneurysm, brain bleed, and carotid artery disease. A meta-analysis of eight studies with over 1.1 million participants did find an increase in the occurrence of cardiac arrest and tachyarrhythmias (racing heart rate accompanied by arrhythmias), but it was not statistically significant.

A meta-analysis of eleven studies with over 3.1 million persons with no prior history of cardiovascular disease found absolutely no effect of ADHD medications on subsequent risk for any cardiovascular event. Another meta-analysis, of eight studies encompassing over 1.8 million individuals with a prior history of cardiovascular disease, reported a higher rate of subsequent occurrence, but it was not considered statistically significant.

The team concluded, “Overall, our meta-analysis provides reassuring data on the putative cardiovascular risk with ADHD medications.” An international team of researchers recently investigated whether medications for attention-deficit/hyperactivity disorder (ADHD) are linked to an increased risk of cardiovascular disease (CVD). They conducted a comprehensive review, known as a meta-analysis, which included 19 studies with nearly four million participants from six countries or regions: the United States, South Korea, Canada, Denmark, Spain, and Hong Kong.

The findings from the entire data set showed no significant link between the use of any ADHD medications and the occurrence of cardiovascular events. This lack of association was consistent across all age groups: children and adolescents (12 studies with over 1.7 million participants), young and middle-aged adults (7 studies with over 850,000 participants), and older adults (6 studies with over 250,000 participants).

The researchers also compared the effects of stimulant medications against non-stimulant medications on cardiovascular risk. Both categories showed no significant risks in a meta-analysis of 17 studies with more than 3.8 million participants for stimulants, and three studies with over 670,000 participants for non-stimulants.

Further analysis differentiated between types of cardiovascular risks, such as myocardial infarction (heart attack) and cerebrovascular diseases (like stroke, brain aneurysm, and carotid artery disease). Again, stimulant medications showed no significant impact on these conditions in studies involving over 900,000 participants each. However, a review of eight studies with over 1.1 million participants suggested a slight increase in incidents of cardiac arrest and tachyarrhythmias (a racing heart rate with irregular rhythms), but these findings were not statistically significant.

Additionally, an analysis of 11 studies involving more than 3.1 million people without a prior history of cardiovascular disease found no effect of ADHD medications on the risk of developing cardiovascular events. Likewise, an analysis of eight studies with over 1.8 million individuals who had a history of cardiovascular disease showed a higher occurrence rate of events, but this increase was also not statistically significant.

Conclusion:

The conclusion of the research team was clear: the data is reassuring and does not suggest a substantial cardiovascular risk associated with ADHD medications. Keep in  mind that this reflects current standards of care.  Most guidelines call for monitoring of pulse and blood pressure during treatment so that adverse cardiovascular outcomes can be avoided.

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Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.

Further noting that previous meta-analyses have suggested a link between maternal obesity and increased risk of ADHD in offspring, they set out to also look at paternal obesity.

Only two studies, however, probed the relationship between paternal overweight and obesity and offspring ADHD, making that meta-analysis impractical. A meta-analysis of six studies with a combined total of over a hundred thousand participants found no significant association between overweight or obsess fathers and offspring mental disease of any kind (with all such disorders lumped together). There was no indication of publication bias and little variability (heterogeneity) between studies.

Ten studies with a combined total of over 800,000 participants, however, examined the relationship between overweight and obese mothers and offspring ADHD. Overweight mothers were twenty percent more likely to have offspring with ADHD. Obese mothers were more than fifty percent more likely to have offspring with ADHD. There was absolutely no sign of publication bias in either case. Inter-study heterogeneity was negligible for overweight, and moderate for obesity.

The team concluded, “We found that the most recent evidence indicates the detrimental connections between parental pre-pregnancy overweight/obesity and offspring mental health.” That is perhaps a bit overstated, as the only clear sign was with maternal overweight or obesity.

ADHD is associated with impaired executive functions. These functions, associated with the prefrontal cortex, control thoughts and goal-oriented behaviors, including inhibition, cognitive flexibility, and working memory.

To what extent can meditation-based mind-body interventions (MBIs) such as yoga, Tai Chi, Qigong, and Mindfulness improve symptoms and executive functioning in persons with ADHD?

To explore this question a Chinese study team performed a systematic search of the peer-reviewed medical literature for randomized controlled trials (RCTs) in either Chinese or English that could be subjected to meta-analysis.

Nineteen RCTS, all but one in English, met criteria for inclusion. Nine involved children and adolescents, and ten involved adults. Fifteen of the studies looked at mindfulness, two at yoga, and two at Tai Chi.

Eight studies were rated as high quality, and the other eleven moderate quality. However, “none of the studies succeeded in blinding participants and therapists due to the challenges of performing double-blind procedures in non-pharmacological studies.”

A meta-analysis of fourteen RCTs totaling 832 participants found small but significant improvements for inattention symptoms. Longer trainings (over 16 hours total) increased the effect size to small-to-medium. Trainings were more successful with adults (small-to-medium effect size) than with children and adolescents (improvements not significant). 

Another meta-analysis, of fifteen RCTs combining 868 participants, likewise reported small but significant improvements for hyperactivity/impulsivity symptoms. In this case the trainings were more successful with children and adolescents than with adults, where outcomes lost significance. Longer trainings (over 16 hours total) did not improve outcomes, and in fact made gains insignificant.

A third meta-analysis, of ten RCTs with a combined 558 participants, found small-to-medium effect size improvements in executive functioning. Trainings were effective for all ages. Longer trainings (over 16 hours total) increased the effect size to medium. Direct measurement of behavioral tasks, as opposed to relying on questionnaires, likewise increased the effect size to medium. 

For all three meta-analyses, there was virtually no between-study variation (heterogeneity), meaning these outcomes were consistent across studies. There were also no signs of publication bias.

Overall, MBIs improved ADHD symptoms with small effect size, but executive functioning – arguably the more important of the two criteria for ultimate well-being – with medium effect size when measured directly after over 16 hours of training. 

The authors concluded, “This meta-analysis confirmed that MBIs, such as mindfulness, Tai Chi, and yoga, had small to medium intervention effects on ADHD symptoms and EF [executive function] compared with the control condition. Although the results of the subgroup analysis suggest that age, interventions, and total time may be important moderators affecting MBIs intervention on the symptoms (inattention, hyperactivity/ impulsivity) of ADHD, while interventions and total time may be moderators affecting EF, more research needs to be conducted to support these findings.”