The first risk genes for ADHD has been identified

A major international collaboration headed by researchers from the Danish iPSYCH project, the Broad Institute of Harvard and MIT, Massachusetts General Hospital, SUNY Upstate Medical University, and the Psychiatric Genomics Consortium has for the first time identified genetic variants which increase the risk of ADHD. The new findings provide a completely new insight into the biology behind ADHD.

 

Risk variants for  ADHD
Our genes are very important for the development of ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for locations in the genome with genetic variation that is involved in ADHD has not delivered clear results. A large genetic study performed by researchers from the Psychiatric Genomics Consortium have compared genetic variation across the entire genome for over 20,000 people with ADHD and 35,000 who do not suffer from it – finding twelve locations where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant.

The special about the new study is the large amount of data. The search for genetic risk variants for ADHD has spanned decades but without obtaining robust results. This time the study really expanded the number of study subjects substantially, increasing the power to obtain conclusive results.

The results of the study have just been published in the scientific journal Nature Genetics.

The new genetic discoveries provide new insights into the biology behind developing ADHD. For example, some of the genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning. Overall, the results show that the risk variants typically regulate how much a gene is expressed, and that the genes affected are primarily expressed in the brain.

The same genes affect impulsivity in healthy people
In the study, the researchers have also compared the new results with those from a genetic study of continuous measures of ADHD behaviours in the general population. The researchers discovered that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population. This result tells us, that the risk variants are  widespread in the population. The more risk variants a person has, the greater the tendency to have ADHD-like characteristics will be as well as the risk of developing ADHD.
The study also evaluated the genetic overlap with other diseases and traits, and a strong negative genetic correlation between ADHD and education was identified. This means that on average genetic variants which increase the risk of ADHD also influence performance in the education system negatively for people in the general population who carry these variants without having ADHD.

Conversely, the study 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.

What´s next?
The new findings mean that the scientists now – after many years of research – finally have robust genetic findings that can inform about the underlying biology and what role genetics plays in the diseases and traits that are often cooccurring with ADHD. In addition, the study is an important foundation for further research into ADHD. Studies can now be targeted, to focus on the genes and biological mechanisms identified in the new study in order to achieve a deeper understanding of how the genetic risk variants affect the development of ADHD with the aim of ultimately providing better help for people with ADHD.


References:

Demontis and Walters et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 2018. https://doi.org/10.1038/s41588-018-0269-7

https://www.nature.com/articles/s41588-018-0269-7

Beneficial effects of high-intensity exercise on the attentive brain

Physical exercise and the brain

Emerging evidence from research studies suggests that physical activity can improve attention, brain function and well-being. In an attempt to understand more about the beneficial effects of high-intensity exercise, we recently conducted a study on the effect of PHysical Activity on Brain function (PHAB study). We examined whether cycling at a high intensity for 20 minutes would improve brain-activity (electroencephalography; EEG) measures of attention and focus during computerised tasks. We also aimed to investigate whether some individuals, for example those who are physically fit, would benefit more or less from exercise.

PHAb setup2

Does high-intensity exercise improve attention?

Participants (young adult men) were invited to our research centre, where they completed computer tasks while we recorded their brain activity. In the first task, they were asked to respond to letter ‘X’ following an ‘O’, but not to respond if another letter was presented after an ‘O’. Participants performed the task both before and after exercise and rest, and so we were able to test if their brain activity changed after exercise.

Task

We found that an attention measure called the “P3” was enhanced after exercise but not after rest. This suggests that the intense exercise session led to improvements in their attention. These improvements in attention from exercise were equal across participants, regardless of how physically fit they were.

The participants also performed two subsequent computer tasks, but we did not find improvements after exercise in these tasks. We believe that the beneficial effects of exercise may have worn off by the time that they performed these tasks.

These results suggest that intense exercise may improve attention. Exercise may therefore be beneficial for individuals with impairing levels of inattentive and restless behaviours, such as ADHD. This is currently being tested in the clinical trial CoCA (https://mind-the-gap.live/2018/10/09/10-weeks-of-physical-exercise-or-light-therapy/) (https://mind-the-gap.live/2017/02/18/coca-proud-trial-ready-to-roll/).

Read more about our study results at:

https://www.sciencedirect.com/science/article/pii/S0166432818308490

If you have any questions

Please feel free to contact Professor Jonna Kuntsi (jonna.kuntsi@kcl.ac.uk). The project was supported by a Medical Research Council studentship to Ebba Du Rietz.

Phelps

 

Ebba Du Rietz and Jonna Kuntsi

ADHD in ancient Greece?

One often hears that the first written description of ADHD stems from the book of the German physician Melchior Adam Weikard “Der Philosophische Arzt” (translated: “The philosophical doctor”) published in 1775. Other well-known old descriptions include for example George F. Still’s description from 1902 published in the Lancet, and Alexander Crichton’s description from 1798. However, this year a Brazilian research group published a report where they claim that the first know description of ADHD, or at least ADHD-like behavior, might be more than 2000 years old!*

The philosopher Theophrastus was a former pupil of Plato and Aristotle who lived in ancient Greece. In approximately 319 years BC he wrote “The Characters”, which essentially is a collection of texts that describes the behavior of 30 stereotypical characters where each character is devoted 10-15 phrases. One of these characters, “the obtuse man”, is an adult man who is described to have both inattention symptoms (forgets important appointments) and hyperactivity symptoms (tires out his children while playing). In addition, “the obtuse man” also has sleep problems and has problems with planning, which both are more common among individuals with ADHD than among those without.

Despite that it can be argued that the behavior of the “the obtuse man” is not a perfect description of typical ADHD, it is still interesting that the oldest known description of ADHD-like behavior describes these symptoms in an adult, in contrast to the later descriptions of ADHD-like behavior that are about children with these symptoms. Moreover, Theophrastus’ more than 2000-year-old text further supports that ADHD (and other psychiatric disorders) has been a part of human life as long as we have been humans.

*Victor MM, Bruna SdS, Kappel DB, Bau CH, Grevet EH. Attention-deficit hyperactivity disorder in ancient Greece: The Obtuse Man of Theophrastus. Aust N Z J Psychiatry. Jun 2018;52(6):509-513.

Tor-Arne Hegvik is medical doctor who is doing research on ADHD and its co-morbidities as a part of the CoCA project: https://coca-project.eu/

Picture from https://pixabay.com

ADHD Is A Risk Factor For Type Two Diabetes And High Blood Pressure, As Well As Other Psychiatric Disorders

All Swedish residents have their health records tracked through unique personal identity numbers. That makes it possible to identify psychiatric and medical disorders with great accuracy across an entire population, in this case encompassing more than five and a half million adults aged 18 to 64. A subgroup of more than 1.6 million persons between the ages of 50 and 64 enabled a separate examination of disorders in older adults.

Slightly over one percent of the entire population (about 61,000) were diagnosed with ADHD at some point as an adult. Individuals with ADHD were nine times as likely to suffer from depression as were adults not diagnosed with ADHD. They were also more than nine times as likely to suffer from anxiety or a substance use disorder, and twenty times as likely to be diagnosed with bipolar disorder.  These findings are very consistent with reports from clinical samples in the USA and Europe.

Adults with ADHD also had elevated levels of metabolic disorders, being almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes. Persons with ADHD but without psychiatric comorbidities were also almost twice as likely to have high blood pressure, and more than twice as likely to have type 2 diabetes.

Similar patterns were found in men and women with ADHD, although comorbid depression, bipolar disorder, and anxiety were moderately more prevalent in females than in males, whereas substance use disorder, type 2 diabetes, and hypertension were more prevalent in males than in females.

ADHD was less than a third as prevalent in the over-50 population as in the general adult population. Nevertheless, individuals in this older group with ADHD were twelve times as likely to suffer from depression, anxiety, or substance use disorders, and more than 23 times as likely to be diagnosed with bipolar disorder as their non-ADHD peers. They were also 63% more likely to have high blood pressure, and 72% more likely to have type 2 diabetes.

The authors noted, “Although the mechanisms underlying these associations are not well understood, we know from both epidemiologic and molecular genetic studies that a shared genetic predisposition might account for the co­existence of two or more psychiatric conditions. In addition, individuals with ADHD may experience increased difficulties as the demands of life increase, which may contribute to the development of depression and anxiety.” As for associations with hypertension and type 2 diabetes, these “might reflect health ­risk behaviors among adult patients with comorbid ADHD in addition to a shared biological substrate. As others have noted, inattention, disinhibition, and disorganization associated with ADHD could make it difficult for patients to adhere to treatment regimens for metabolic disorders.” They concluded that “Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.”

Stephen Faraone is distinguished Professor of Psychiatry and of Neuroscience and Physiology at SUNY Upstate Medical University and is working on the H2020-funded project CoCA. 

REFERENCES

Qi Chen, Catharina A. Hartman, Jan Haavik, Jaanus Harro, Kari Klungsøyr, Tor­Arne Hegvik, Rob Wanders, Cæcilie Ottosen, Søren Dalsgaard, Stephen V. Faraone, Henrik Larsson, “Common psychiatric and metabolic comorbidity of adult attention-deficit/hyperactivity disorder: A population-based cross-sectional study,” PLoS ONE (2018), 13(9): e0204516. https://doi.org/10.1371/journal.pone.0204516.

Living day-to-day with ADHD and experience of the CoCA clinical trial

Below is a recent interview from a patient who took part in the PROUD study in London  I would like to thank him for taking the time to answer my questions, his articulate descriptions provide a fascinating insight into what it is like to live with ADHD on a daily basis and his reflections on the PROUD clinical trial, provide us, as researchers, a valuable insight into what it is like to participate from the perspective of a patient.

  1. What is it like to live with ADHD?

Please describe your main symptoms. Have your symptoms changed since childhood vs. adulthood?

I find myself easily distracted. It is very difficult for me to carry out long tasks that require a lot of attention or very tedious tasks. I have racing thoughts going through my head 24/7 and it is very difficult for me to shut them off and focus on what I am doing. I also find myself experiencing mood swings very often. I have multiple highs and lows throughout the day and it is very difficult for me to maintain a stable mood. Also, when I read it is very difficult for me to retain the information and remember what I have just read. I also have trouble trying to organize my thoughts and speak in fluent sentences because my mind is thinking about so many things and I just want to get all of them out.

I would say my symptoms have gotten worse as I transition into adulthood, but it could be because I am more aware of what is going on and the science behind it. I always had anxiety when I was a kid but never really depression. I notice that as I get older I find I get down into slumps and feel really unmotivated. That is the main difference from my childhood and adulthood experiences.

When were you diagnosed with ADHD? By whom? How did you feel about getting the diagnosis?

I was diagnosed when I was roughly 12 years old. I went to see a Doctor to get tested because my reading comprehension was very low and my test taking ability was terrible as well. They discovered that I had ADHD as well as Performance Anxiety.

As a kid, you never want to be told that there is something wrong with you, but it was good to know why I was having the thoughts I had and what exactly was going on. This led me to do extensive research on these mental illnesses and get a better understanding of what was going on and how to better handle my symptoms.

How have you been treated (medication/ psychotherapy)? What are the effects?

I was treated for my anxiety with Anti-depressants as a kid but came off of them due to them making me emotionally numb. I was never treated for my ADHD as a kid because the doctors thought that Anxiety was the main culprit of my problems, but I have actually discovered that ADHD is the main issue.

I did have a psychiatrist for a while as a kid, but I can’t remember much from the sessions and I don’t think they were very helpful. I did do CBT towards the end of 2017 and that did prove to be quite helpful. I just recently decided to get treated for my ADHD with medication just after I finished the Trial at Kings College because I felt that my symptoms were really beginning to affect my life. So I am currently on 40 mg Elvanse and I am on the waiting list for CBT to try and give psychotherapy another shot.

How does ADHD influence your life? (Work, friends/partnership, hobbies etc.)

I am an Actor, so remembering lines and understanding things thoroughly is absolutely crucial! My ADHD comes in the way a bit because sometimes I zone out and don’t completely listen to instructions or other actors. Also, reading scripts can be a bit difficult in trying to retain the information and focus on what I am reading.

I find that it hinders my relationships because I am a bit all over the place sometimes and do not give my friends or family the time or attention they deserve. I have also found that my ADHD causes regular mood swings so sometimes I am feeling depressed and do not feel like doing anything. This affects my work and relationships as well as my hobbies.

Do your friends/ colleagues know about your illness?

Yes, they do. I find it extremely important that everyone understands why I may act strange sometimes and also, they will understand me better. It is not something that I am ashamed of. It is just the way my brain works.

What is the worst thing about having ADHD?

The biggest issues are not being able to focus or getting easily distracted. Another of the big issues I have is the depression side of things. It also drains all of my energy and I end up not feeling like doing anything.

Do you think ADHD has any positive influences in your life?

One of the big benefits of having ADHD is always planning everything! I have to always be very prepared, but it is also a bad thing because it causes me anxiety sometimes. But then again, I don’t believe I would be the same person I am now if I didn’t have these issues.

  1. Study and Intervention

How did you learn about the study?

I believe I learned about the study from the Clinicaltrials.org website.

What motivated you to participate?

I absolutely love psychology and I am always interested in learning about the things that affect me personally. I am always doing research on mental health because it allows me to get a better understanding of what is happening on a more scientific level. It gives me more insight and allows me to better deal with my symptoms.

What were your expectations about the study before you started?

I expected to get a better understanding of ADHD and even finding a new strategy on coping with my symptoms.

Which intervention did you participate in, when?

Exercise intervention.

What did you like about the intervention? What did you dislike?

I liked the fact that it kept me busy and it also forced me to be proactive and accountable because I couldn’t lose the phone or the wrist band tracker. It made me work on that aspect of my ADHD because I do tend to forget to do things and I am always losing things. I also found that my depression is onset when I am not doing anything so having to be accountable for this exercise and doing what I was supposed to do kept my mind busy.

The only thing I didn’t like was the wrist band and having the wear it all the time because it is quite unattractive, and I do travel a lot so having to keep it while traveling it abroad and charging everything was just a bit overwhelming.

Was the intervention helpful? (Any effects on ADHD core symptoms, mood, sleep, weight, fitness etc.?)  

I am already a very active person, so it didn’t really change anything as far as fitness goes. It helped my sleep patterns because I was more aware of how much I was sleeping because I had to write it down. I feel like it helped my mood a bit because I was focused on phone ringing and answering the questions, so my mind was wandering off and causing me depression.

Was it difficult/easy to use the App?

The app was extremely easy to use but it was a bit tedious when it would go off every hour or so and was a bit annoying when I was busy or working. Not to mention that I couldn’t cover up the tracker with a sleeve or a jacket because of the light sensor.

Would you recommend other people with ADHD to participate in the study? Why?

Yes I would because I feel like it gives people a better understanding of their mental health and gives them some helpful things that they can take away from the study to implement into their life. Having a mental illness does not mean you are less of a person or less capable, but it is just important to understand what is going on. If you understand what is causing the symptoms, then it is easier to find ways to overcome these issues.

 Any suggestions/ways that the researchers could improve the experience for people in this study?

I would recommend updating the technology and having a more advanced wrist band sensor that looks more like a watch like apple watches or fitbits. It is an amazing study and I am very happy with how it was conducted. I wish I could offer more ways that you could improve the study, but my experience has been extremely satisfying.

Adam Pawley is a clinical neuroscientist at King’s College London. He is running the CoCA PROUD trial in London.

ADHD at childhood and the risk of obesity later in life

file

Really?

Having ADHD at childhood could increase the obesity risk later in life? Oddly enough, YES. There is increasing knowledge of scientific evidence about a positive link between this mental disorder and the risk of weight gain throughout life.

Is there any explanation for this relationship?

So, being hyperactive as a child can make that child to accumulate more body fat in the future? this is quite ambiguous. Let’s enlighten this matter. The ADHD is a neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The factors contributing to the comorbidity between ADHD and obesity are supposed to be a genetic influence, fetal programming, executive dysfunctions, psychosocial stress, sleep patterns alterations, and factors directly related to energy balance (Hanć & Cortese, 2018). Among the last ones, it can be hypothesized that four inter-related mechanisms could partly explain why an ADHD brain is hard-wired for weight gain. These are low levels of physical activity, low physical fitness, sedentary behaviors, and overeating. Thus, individuals diagnosed with ADHD are more likely to do a less physical activity, to have a low fitness level, be more sedentary and eat more than they need than people without this disorder.

ADHD at childhood as a predictor of obesity across the life course

ADHD individuals have more complications to lead a healthy lifestyle in comparison with non-ADHD due to psychological dysfunctions. In addition, obesogenic factors are likely to accumulate over the life course of individuals. Collectively, children having ADHD and with an unhealthy lifestyle might become chronic, resulting in the development or maintenance of obesity later in life.

So, what can a child with ADHD do to avoid or reduce the risk of obesity in the future?

Youth aged between 6-17 years old can do a more physical activity, diminish sedentary behavior and eat healthier to avoid obesity later in life. Regarding physical activity guidelines, youth should perform 60 minutes or more of physical activity daily, as part of this they should do moderate-to-vigorous aerobic exercise, muscle strengthening activities and bone strengthening exercises at least 3 days per week. Also, sedentary behavior in youth should be limited <2 hours per day, and fruits and vegetables are recommended daily.

Take home message

Exercise your brain while your body!

References

Hanć, T., & Cortese, S. (2018). Attention deficit/hyperactivity-disorder and obesity: A review and model of current hypotheses explaining their comorbidity. Neuroscience & Biobehavioral Reviews, 92, 16–28.

Adrià Muntaner-Mas, Antonio Martinez-Nicolas and Francisco B. Ortega 

http://profith.ugr.es/

Mini-documentary: “Shine a light – understanding ADHD”

On the last day of the international ADHD Awareness Month, we are releasing a mini-documentary about ADHD. The hope is that this video will help young people and adults diagnosed with ADHD, or who suspect they have ADHD, as well as their family and friends, to understand the condition better.

“I feel like a universe, stuffed within a shoebox” – this is how Bryn Travers describes what it’s like to have Attention Deficit / Hyperactivity Disorder (ADHD). In this short film we have asked people with ADHD and their relatives about living with ADHD: what are the challenges and what are the things they like about ADHD? We have also asked clinicians and researchers working with ADHD to explain more about the origins of the disorder, what they have learnt from their experience working with patients, but also what are the main questions that research is trying to answer about ADHD.

Many children, adolescents and adults suffer from ADHD. ADHD is a complex disorder that affects people differently. Generally people experience problems in daily life, especially with respect to controlling attention, impulses and emotions. At the same time, people with ADHD enjoy their creativity and positive energy. Medication is effective for many people with ADHD, but not for all. That is why many people are interested in other types of (additional) treatment, such as meditation or diets. These types of treatment should therefore be better investigated. Knowing more about ADHD and spreading awareness will help people to understand what causes their behaviour. This will reduce stigma and (self)blame.

The video features four of the most well-known researchers in the field of ADHD: dr. Eric Taylor is emeritus professor of Child and Adolescent Psychiatry at King’s College London, dr. Philip Asherson is professor of Molecular Psychiatry at King’s College London, dr. Barbara Franke is professor of Molecular Psychiatry at Radboud university medical center Nijmegen (The Netherlands), and dr. Corina Greven is psychologist and behavioural geneticist at Radboud university medical center Nijmegen. Next to these scientists and psychiatrists, we see three people with ADHD (Bryn Travers, Evie Travers and Aziz), Andrea Bilbow, president of patient organisation ‘ADHD Europe’ and mother of two children with ADHD, and dr. Kai Syng Tan, researcher and artist at King’s College London, who also has an ADHD diagnosis.

This film was created through the MiND research consortium, in collaboration with the consortia Aggressotype, CoCA and Eat2beNICE. These consortia are all funded by the European Commission through the FP-7 and horizon2020 programs. Young researchers dr. Nicoletta Adamo and Laura Ghirardi are the brains behind this film, with the help of the MiND training program and 4QuarterFilms.

Do you want to help us spreading awareness about ADHD? Then share this video with everyone you know! The video also contains subtitles in English, Dutch, German, Spanish, Italian, Swedish and Hungarian (and more languages may follow).

You can watch the video here: