July 4, 2021
Our genes are very important for the development of mental disorders-including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results. In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component. Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH. We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish psych group, which had access to many samples.
The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it - finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant. The results of the study have just been published in the scientific journal Nature Genetics, https://www.nature.com/articles/s41588-018-0269-7.
These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.
Our study used the genome-wide association study (GWAS)methodology because it allowed us to discover genetic loci anywhere on the genome. The method assays DNA variants throughout the genome and determines which variants are more common among ADHDvs. control participants. It also allowed for the discovery of loci having very small effects. That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.
The main findings are:
A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD. None of these loci were traditional candidate genes' for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications. Instead, these genes seem to be involved in the development of brain circuits.
B) we found a significant polygenic etiology in our data, which means that there must be many loci(perhaps thousands) having variants that increase the risk for ADHD. We will need to collect a much larger sample to find out which specific loci are involved;
We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population. This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population. These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants
The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions: Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders. These analyses found a strong negative genetic correlation between ADHD and education. This tells us that many of the genetic variants which increase the risk for ADHD also make it more likely that a person will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI, and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population. This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD. When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.
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.
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.
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.
In open-ended taped interviews of up to an hour in length, each was asked three questions:
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.”
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.”
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/.
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.
China is the outstanding economic growth story of the early twenty-first century. According to the World Bank, China has “experienced the fastest sustained expansion by a major economy in history – and has lifted more than 800 million people out of poverty.”
That expansion has been accompanied by major investments in medical research, and medical treatment capability, especially in the major urban centers that have spearheaded the boom. Life expectancy has risen from 71 in 2000 to 77 in 2019, nearing the U.S. level of 79.
Yet when it comes to pharmaceutical treatment of ADHD, China is an outlier, as revealed by a new study exploring the data in the two main medical insurance programs for its urban population.
The Urban Employee Basic Medical Insurance(UEBMI) covers both employers and employees in public and private workplaces, while the Urban Residents Basic Medical Insurance (BMI) covers the unemployed. As of 2014, these programs cover over 97% of urban residents. The China Health Insurance Research Association (CHIRA) database is a random sampling database from the UEBMI and UBMI databases.
The study population consisted of residents of the 63 cities in the CHIRA database from 2013 through 2017. Prescription prevalence was calculated by dividing the total number of patients prescribed ADHD medications in the CH IRA database by the urban population of the included cities, which was two hundred million as of 2017.
Other studies have found the prevalence of ADHD among Chinese children and adolescents to be about 6.5%, comparable to North American and European countries. Yet, the prescription prevalence of ADHD medications was 0.036% among those aged 0–14 years in 2017 in China. In other words, only about one in every two hundred youths with ADHD were being prescribed pharmaceutical treatments.
For further context, among other economically prosperous countries in Asia, Australia, North America, and Europe, the lowest prescription prevalence of ADHD medications is 0.27% in France, which is still over seven times higher than the Chinese level.
Among Chinese urban dwellers from 15 through 64 years of age, ADHD prescription prevalence in 2017 dropped by a further order of magnitude (over tenfold) to 0.003%, and among those 65 and older, to a scant 0.001%.
The Chinese study team suggested several likely contributing factors:
