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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.”

A transcontinental study team (California, Texas, Florida) used a nationally representative sample – the 2018 National Survey of Children’s Health – to query 26,205 caregivers of youth aged 3 to 17 years old to explore inequities in ADHD diagnosis.  

With increasing accessibility of the internet in the U.S., more than 80% of adults now search for health information online. Recognizing that search engine data could help clarify patterns of inequity, the team also consulted Google Trends.

The team noted at the outset that “[d]ocumenting the true prevalence of ADHD remains challenging in light of problems of overdiagnosis (e.g., following quick screening rather than full evaluation incorporating multi-informant and multi-method data given limited resources) and underdiagnosis (e.g., reflecting inequities in healthcare and education systems).” Underdiagnosis is known to be influenced by lack or inadequacy of health insurance, inadequate public health funding, stigma, sociocultural expectations in some ethnic groups, and structural racism, among other factors.

After controlling for poverty status, highest education in household, child’s sex, and child’s age, the team reported that Black youth were a quarter (22%) less likely to receive ADHD diagnoses than their white peers. Latino/Hispanic youth were a third (32%) less likely and Asian youth three-quarters (73%) less likely to receive ADHD diagnoses than their white peers.

The team also found that state-level online search interest in ADHD was positively associated with ADHD diagnoses, after controlling for race/ethnicity, poverty status, highest education in household, child’s sex, and child’s age. However, the odds ratio was low (1.01), “suggesting the need for additional evaluation.” Furthermore, “There was no interaction between individual-level racial/ethnic background and state-level information-seeking patterns. … the state-level online information-seeking variation did not affect the odds that youth of color would have a current ADHD diagnosis over and above other included characteristics.” 

That could be due in part to the gap in high-speed broadband access between Black and Hispanic in contrast to white populations, but that would not explain the even larger gaps in diagnosis for Asian youth, who tend to come from more prosperous backgrounds.

The team concluded, “Persistent racial/ethnic inequities warrant systematic changes in policy and clinical care that can attend to the needs of underserved communities. The digital divide adds complexity to persistent racial/ethnic and socioeconomic inequities in ADHD diagnosis …”

Parkinson’s disease is a chronic, progressive neurological disease, characterized by the drastic reduction of dopamine transporters and the dopaminergic neurons upon which they are expressed. The resulting symptoms include bradykinesia (slowness of initiation of voluntary movements), tremors, rigidity, and postural instability.

Taiwan’s National Health Service covers about 99 percent of its 24 million inhabitants and maintains complete records in its National Health Insurance Research Database. The Longitudinal Health Insurance Database2000 (LHID 2000) is a nationally representative subset of the latter.

Using the LHID 2000, a Taiwanese research team identified 10,726 patients with Parkinson’s disease. It paired them with an identical number of randomly selected non-Parkinson’s controls, matched by age, gender, and index date (first date of diagnosis of Parkinson’s disease).

The team then looked retroactively through the database to determine which of the 21,452 individuals had previously been diagnosed with ADHD. Fourteen of the 10,726 Parkinson’s patients had been diagnosed with ADHD, versus five of the 10,726 in the control group.

Parkinson’s patients were thus 2.8 times as likely to have had a previous diagnosis of ADHD as the controls. When adjusted for age, gender, and Carlson Comorbidity Index scores, they were 3.6 times as likely to have had a previous ADHD diagnosis.

The authors cautioned that this association between prior ADHD diagnosis and subsequent Parkinson’s diagnosis is not causal.

Only one in 766 of Parkinson’s patients (a seventh of one percent) had previously been diagnosed with ADHD. So even if there were any causal relationship, it would be extremely weak.

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What are we to make of adults who exhibit the diagnostic criteria for ADHD, but are nevertheless high-functioning and successful? A trio of British investigators has just published six case studies that explore this question.  It would have been better for them to have conducted a much larger, controlled research study but, in the absence of such data in the area, these case studies are intriguing and may help guide more informative research.

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The authors recruited six successful men between the ages of 30 and 65 from a National Health Service tertiary service in London. Four were in long-term relationships, with children. All had good jobs.
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In open-ended taped interviews of up to an hour in length, each was asked three questions:

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1.     What do you think are the advantages and disadvantages of having ADHD?
2.     Please describe a time when you felt that your ADHD helped you to achieve something?
3.     What aspects of your ADHD would you miss if it went away?

Hyper-focus in ADHD is generally considered a deficit, inset-shifting, and task-switching. But the authors report that participants associated it with productivity. One said, “I think the energy that the ADHD brain seems to have....it’s unfocused, quite scattered, chaotic and a bit random...but give that brain something that you can tune into, and it’s your interest, then all that random stuff just goes boom... I get this incredible intense concentration and that’s great for work.”
Participants also saw advantages in divergent thinking, with one stating, “I’m an artist.... a creative type... a Bohemian.... you are most likely to be a creative person if you are a divergent thinker....and not convergent... I am very creative and that’s through and through... I’m a fine art graduate, a musician, a published poet, an entrepreneur, a performer.”

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All the participants reported being seen as nonconformists. Depending on a viewpoint, that can be seen as either detrimental or advantageous.
Impulsivity is a core symptom of ADHD. Participants however related it to bravery, and more specifically adventurousness, spontaneity, and thrill-seeking. One said, “thrill-seeking is an ADHD thing... I can list in my life have done white water rafting, bungee jumping, hand-glider pilot … I have done a lot in my life and achieved a lot and experienced a lot... Furthermore, I would see a lot of that as being quite positive, and a lot of that is ADHD drive.”
Another common theme was high energy and “spirit.” One participant said, “I’ve got all this energy.... a lot of energy... whatever it's to do with... nature/nurture/spiritual stuff.”

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These testimonials are useful as a check on the usual narrative of impairment. ADHD does not predestine all it afflicts to an unfulfilling life. Many, often assisted by medication, still lead exciting, successful, rewarding lives.   Yet, we must be cautious in concluding that these individuals were successful because of their ADHD.  It is possible, even likely, that they had other strengths such as high intelligence that compensated for their ADHD symptoms.  We can not know from this report if their lives had been even more fulfilling or successful in the absence of ADHD.   See, for example, my blog about highly intelligent people with ADHD:  https://www.linkedin.com/pulse/20141126141502-65669938-smart-people-can-have-adhd-too/.

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While the authors concede that “generalizing the findings of this study is not easy to do,” they inexplicably “also argue that the positive aspects we found are relevant to other adults with ADHD regardless of sample size, age, gender or ethnicity.”   It is not possible to draw such a definitive conclusion without a much larger sample.
On a hopeful note, they conclude, “This is a study that reaches out to people with lived experience of ADHD: service users, patients, family members, carers, partners, to say that not all symptoms of ADHD are maleficent. Recovery, high functionality, and flourishing with ADHD are possible. Too often people with lived experience hear about ADHD deficits, functional impairments, and associations with substance misuse, criminality, or other disadvantages on almost every level of life (school, work, relationships). … This study affirms the positive human qualities, assets, and attributes in ADHD that can promote and sustain high functioning and flourishing.” I fully endorse the idea that those with ADHD can have wonderful lives, especially if they receive appropriate treatment, both medical and psychological.

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