What have we learned about ADHD comorbidities?

After 5.5 years, the CoCA project has come to an end. In this large-scale European research project, an interdisciplinary group of researchers investigated comorbid conditions of ADHD. They particularly focussed on depression, anxiety, substance use disorder and obesity, as these conditions frequently co-occur with ADHD in adulthood.

What has this extensive study brought us? Experts dr. Catharina Hartman (University Medical Center Groningen, The Netherlands) and prof. dr. Andreas Reif (University Hospital Frankfurt, Germany) were invited by Jonathan Marx for an interview on the online radio program Go To Health Media. In this program they talk about several aspects of the CoCA project: How often do comorbid conditions co-occur with ADHD? What do the genetics of ADHD comorbidities tell us? What should clinicians do to prevent or reduce these comorbidities in ADHD?

As professor Andreas Reif summarizes at the end of the interview, the main things that we learned from the CoCA project are:

  1. Comorbidity in ADHD is a very big problem. Adults with ADHD frequently have co-occuring conditions such as depression, anxiety, obesity and to a bit lesser extent substance use disorder.
  2. The type and prevalence of comorbidities differ between men and women.
  3. There is considerable genetic overlap between ADHD and comorbid conditions. We think that at least part of the overlap between comorbidities is caused by genetic effects (next to environmental effects that also play a role).
  4. The dopamine system plays an important role in comorbidity, through influencing brain processes.
  5. Disturbances in the circadian system (i.e. sleep cycle) are unlikely to play a causal role in these comorbidities, but they might be a consequence.
  6. Clinicans should look out for comorbidities when they treat ADHD patients, and inform their patients about their increased risk to develop comorbidities so that they can take preventive measures (i.e. be careful with alcohol to avoid substance use disorder). Secondly, clinicians should actively look out for ADHD symptoms when treating conditions such as depression, anxiety, substance use disorder or obesity.

Watch the full interview with both experts by clicking on the image below:

More information about the CoCA project: www.coca-project.eu

Just-in-time-adaptive-interventions

Aid for ADHD individuals personal needs, right when it is needed

You might know the tenet of “just in time” from economics. It means bringing goods to a recipient at the right time, exactly when it is needed. But what if we could apply this also to treatments or interventions for mental health problems? Can we provide small interventions at exactly the time when a person needs it? And can this provide us with more insights into what triggers ADHD symptoms?

Just in time economics is possible and required because of dynamic processes in economical markets. Dynamic processes are also present in mental disorders. Attention-deficit/hyperactivity disorder (ADHD) is a condition that is dynamic by nature. Core symptoms of ADHD are hyperactivity, inattention and impulsivity, and many individuals also experience emotion dysregulation. In the past, research focused mainly on how patients with ADHD differ from healthy individuals or other disorders. But what about ADHD individuals’ context or other dynamics, that may trigger symptoms? For this we need to look much more closely at the dynamics of an individual’s life.

Ambulatory Assessment: collecting data in real time and in real life

The Ambulatory Assessment method makes use of smartphones, accelerometers, GPS-tracking and geolocation approaches to track how you feel, what you do, where you go, who you meet, what you eat, and how you’re body is doing (i.e. your heartrate) (1).  This method has improved a lot over years and technical progress makes it more and more feasible to investigate associations between variables over time and how these variables interact in everyday life. This provides researchers with new insights into many different factors that can influence a person’s symptoms and mental health.

The importance of context

The Ambulatory Assessment method also enables to better differentiate between real and deceptive associations. Imagine, a person is asked for hyperactivity in the morning at 9:00 am, noon and evening and it turns out that the person is very hyperactive in the morning. Your conclusion may be that this individual is more hyperactive in the morning, but you don’t know why. If you know more about this person’s context, it may turn out that every day at 08:30 am the person drinks two cups of coffee which causes the measured hyperactivity at 9:00 am. This gives you much more insight into what triggers his or her symptoms.

Another example: imagine that a symptom always occurs in a special situation, at a special place or with a special person (e.g., after trying to catch the connecting train every morning at the same time). If you always ask for symptoms at the same time of day, you may miss this special occasion because it always occurs at another time. This way, you may miss out on important associations between symptoms and situations, places or persons. It is therefore very important to measure symptoms at random time points, or when they are triggered by certain events. This gives you much more informative data.

Cause or consequence?

However, the Ambulatory Assessment method is not yet perfect. The main limitation is that it’s difficult to determine what causes what (2). For example, do fluctuations in mood in patients with ADHD lead to impulsivity or hyperactivity? Or does mood change as a consequence of impulsivity? Another example: Do I feel better after exercising or do I move more because I feel good? Researchers recently found evidence for both directions (3,4).

Towards developing just in time treatment

Let’s think about the next step. A better understanding of causes and consequences and associations between symptoms and environmental triggers in an individual’s real world, creates the basis for just-in-time interventions (6). The idea is to react on dynamics in how symptoms are experienced or triggered, by timing the interventions exactly when it is needed. This could be realized by smartphones or wearables, which are already implemented in Ambulatory Assessment research. These devices are then not only used to collect data in real-time, but also to give feedback and provide interventions to reduce or prevent symptoms.

Exercise intervention through a smartphone app

The antecedent of just-in-time-adaptive-interventions are ecological momentary interventions (EMIs). One example of such an EMI or electronic diary intervention with a smartphone and an accelerometer for individuals with ADHD is the PROUD trial of the European funded project CoCA (5). In this trial, individuals with ADHD received a smartphone and a kind of sports watch (that measures your movement) that together measured their behavior, activity, daylight exposure, mood and symptoms during the day. The smartphone also provided an intervention, either in the form of sports exercises or in the form of bright light therapy. During the exercise intervention, participants are given instructions to perform exercises via a smartphone app by which they are guided through their training by weekly goals, motivational reminders, and training videos. Every evening, they get feedback on performed intervention parameters from that day in real time. This system was not yet so developed that it also changed the type or timing of the intervention to the data that was collected during the day, but that would be the next step to create a just-in-time intervention.

In conclusion, it is important to investigate the associations between ADHD individuals’ symptoms and their personal everyday lives. This helps researchers to understand the dynamic processes behind ADHD and to create tailor-made interventions that can easily be integrated in the everyday life of these individuals. A physician cannot support a patient throughout every step he/she takes, but there are already devices that can be supportive around the clock and technical innovations will surely pave the way to improve personal just-in-time interventions in the near future. 

This blog was written by Elena Koch. She is a PhD student at Karlsruhe Institute for Technology in Germany.

  References

1.        Reichert M, Giurgiu M, Koch ED, Wieland LM, Lautenbach S, Neubauer AB, Haaren-Mack B v., Schilling R, Timm I, Notthoff N, Marzi I, Hill H, Brüßler S, Eckert T, Fiedler J, Burchartz A, Anedda B, Wunsch K, Gerber M, Jekauc D, Woll A, Dunton GF, Kanning M, Nigg CR, Ebner-Priemer U, Liao Y. Ambulatory assessment for physical activity research: State of the science, best practices and future directions. Psychology of Sport and Exercise. 2020;50101742. doi:10.1016/j.psychsport.2020.101742

2.        Reichert M, Schlegel S, Jagau F, Timm I, Wieland L, Ebner-Priemer UW, Hartmann A, Zeeck A. Mood and Dysfunctional Cognitions Constitute Within-Subject Antecedents and Consequences of Exercise in Eating Disorders. Psychother Psychosom. 2020;89(2):119–21. doi:10.1159/000504061

3.        Koch ED, Tost H, Braun U, Gan G, Giurgiu M, Reinhard I, Zipf A, Meyer-Lindenberg A, Ebner-Priemer UW, Reichert M. Relationships between incidental physical activity, exercise, and sports with subsequent mood in adolescents. Scand J Med Sci Sports. 2020;30(11):2234–50.

4.        Koch ED, Tost H, Braun U, Gan G, Giurgiu M, Reinhard I, Zipf A, Meyer-Lindenberg A, Ebner-Priemer UW, Reichert M. Mood Dimensions Show Distinct Within-Subject Associations With Non-exercise Activity in Adolescents: An Ambulatory Assessment Study. Front Psychol. 2018;9268. doi:10.3389/fpsyg.2018.00268

5.        Mayer JS, Hees K, Medda J, Grimm O, Asherson P, Bellina M, Colla M, Ibáñez P, Koch E, Martinez-Nicolas A, Muntaner-Mas A, Rommel A, Rommelse N, Ruiter S de, Ebner-Priemer UW, Kieser M, Ortega FB, Thome J, Buitelaar JK, Kuntsi J, Ramos-Quiroga JA, Reif A, Freitag CM. Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit / hyperactivity disorder: study protocol for a randomized controlled trial. Trials. 2018;19(1):140. doi:10.1186/s13063-017-2426-1

6. Koch, ED, Moukhtarian, TR, Skirrow, C, Bozhilova, N, Ashersn, P, Ebner-Priemer, UW. Using e-diaries to investigate ADHD – State-of-the-art and the promising feature of just-in-time-adaptive interventions. Neuroscience & Biobehavioral Reviews. 2021. https://doi.org/10.1016/j.neubiorev.2021.06.002

The genetic architecture of the brain

Genes play a big role in determining the architecture of our brain: the way it’s folded, the thickness of the outer layer, and the way different brain areas are connected. By combining data from all over the world, a large collaboration of researchers from the ENIGMA consortium has now identified almost 200 genetic variants that are involved in this brain architecture. These findings can help us to further understand the genetics of brain disorders. 

Our genes contain the blueprint of our bodies. They contain information about how our cells function, and they determine for instance the colour of our eyes and hair, or whether we like cilantro (coriander) and bitter tastes. For some traits we know very well how they are influenced by genes. Eye color for instance is coded by only a few genes. But for many other traits such as height and personality, many different genes are involved. In addition, other (non-genetic) factors also influence these traits, such as malnutrition that can cause stunted growth.

The architecture of the brain is influenced by a large numer of genes, of which we still know very little. To investigate this, researchers combined genetic data of over 50.000 individuals with MRI-data. MRI-scans can show in detail the thickness of the outer layer of the brain, where all the brain cells are (also called the grey matter). They can also be used to measure how much this layer is folded, which gives information about the total surface of this outerlayer. This brain architecture is unique to every individual. The extent of the folds and the thickness of the outer layer have previously (in other research studies) been linked to cognitive abilities and various neurological and psychiatric disorders, such as Alzheimer’s disease, schizophrenia, depression, autism, and ADHD. It is therefore helpful to understand the genetics of this architecture, because it will help us to better understand the genetic mechanisms of these conditions.

The findings from this research study are also explained in this video:

This important research can only be done by combining a lot of data and collaborating with a large number of scientists and institutes. The ENIGMA consortium has been set upt to facilitate this kind of world-wide collaboration. The research that has now been published is the combined effort of more than 360 scientists from 296 departments across 184 different institutions and universities. They also made their results downloadable so that everyone who is interested can have a closer look.

The full publication can be found here: https://science.sciencemag.org/content/367/6484/eaay6690

See also our previous blogposts about these topics:

 

 

 

These are the world’s most high ranking experts on ADHD

Who are the most knowledgeable people about ADHD in the world? According to the website expertscape.com, these are professors Stephen Faraone (SUNY upstate University), Samuel Cortese (University of Southampton) and Jan Buitelaar (Radboud University Nijmegen).

What’s more, several scientists who are involved in our research consortia that investigate ADHD (i.e. Aggressotype, CoCA, IMpACT, Eat2beNICE) are top-ranked in this list of more than 30.000 possible experts in the field. These include Stephen Faraone, Jan Buitelaar, Philip Asherson, Barbara Franke, Joseph Antoni Ramos-Quiroga, Henrik Larsson, Catharina Hartman and Pieter Hoekstra. What this means is that the ADHD research that we do, and that is often reported on in this blog, is lead by the world’s top ADHD experts.

adhdexperts_pic
‘Our’ top-ranked ADHD experts. From left-to-right: Stephen Faraone, Jan Buitelaar, Philip Asheron, Barbara Franke, Joseph Antoni Ramos-Quiroga, Henrik Larsson, Catharina Hartman, Pieter Hoekstra.

How is an expert defined?

The website expertscape was started by John Sotos when he was looking for an expert on Parkinson’s disease to treat his uncle. This turned out to be more difficult than he thought. As John Sotos was a doctor himself, he luckily had a large network of doctors that he could contact about this. But this made him realise that people who don’t have such a network, would not be able to find out who the most knowledgeable persons are on a particular topic. He therefore created this website expertscape.com

The way the website works is quite simple: it searches for academic, peer-reviewed publications by a certain person on a certain topic. The more someone has published on a topic, the higher this person is ranked. Thus,  “[a]n expert is not just someone who knows a lot about a particular topic. We additionally require that the expert write about the topic, and be involved at the leading edge of investigation of the topic.”

This means that the site is actually not a very good tool to find a good doctor. As the website acknowledges “a great doctor has many important qualities beyond expert knowledge of your very specific medical condition.” However, it does mean that the website is pretty good at providing a simple overview of who has a lot of scientific knowledge about a specific topic.

So are they really experts?

In the past years I have met with most people in the top of this list, and I dare say that they are very knowledgeable indeed. Each of them has been working in the ADHD field for a considerable amount of time and has added important new insights into ADHD through research and publications. What I find most striking from this list however, is that most of these experts work together in consortia and international networks. And that is how the field really moves forward: by combining the knowledge of all these experts.

Several of these experts have also written for this blog:

 

Source: http://expertscape.com/ex/attention+deficit+disorder+with+hyperactivity

 

This blog was written by Jeanette Mostert. Jeanette studied brain connectivity in adult ADHD during her PhD. She is now dissemination manager of the international consortia CoCA and Eat2beNICE. 

 

It’s ADHD Awareness Month – know the facts and bust the myths!

It’s October, and that means that it’s ADHD Awareness Month again. Throughout this month people all across the globe will be raising awareness about Attention Deficit Hyperactivity Disorder (ADHD). As ADHD researchers, we of course contribute to this by sharing with you what we know – and what we yet don’t know – about ADHD.

To start off, let’s re-watch the beautiful mini-documentary that was created last year: Shine a light – understanding ADHD. In this video we see several people with ADHD as well as ADHD researchers, who all explain how they see, experience and investigate ADHD.

This year’s ADHD Awareness Month is about myths and facts. On this website you can find some very nice articles that clearly explain the facts: for instance why ADHD is not an excuse for laziness, and why about half of the children with ADHD do not grow out of it when they reach adolescence and adulthood. For this last reason, many of us are studying ADHD in adulthood. For instance in the IMpACT research consortium.

In a few weeks we will be releasing a series of videos in which some more myths about ADHD are being debunked. These videos are being created by researchers from the CoCA-consortium. The research done in this consortium is aimed to stop the spiral from ADHD into depression and obesity, as was written in this nice article by the European Commission.

Another intersting new research theme is whether lifestyle choices such as diet and exercise can influence how we behave and feel. If you want to learn more about this, I refer you the website New Brain Nutrition, which has several very interesting learning modules, as well as a nice blog.

We hope that through these websites we inspire you to learn more about ADHD. Know the facts, and bust the myths!

 

More information:

http://www.adhdeurope.eu

http://www.adhdawarenessmonth.org

http://www.coca-project.eu

http://www.newbrainnutrition.com

http://www.impactadhdgenomics.com

https://ec.europa.eu/research/infocentre/article_en.cfm?artid=50905

 

10 Years of progress in Adult ADHD

This year will celebrate 10 years of the UK Adult ADHD Network. During that time we have seen a rapid advance in our understanding of ADHD across the lifespan, the availability of diagnostic services and access to effective treatments. Advances seen in the UK are also seen in many other countries across the EU and worldwide.  The meeting will highlight key advances in our understanding of course and outcome; genetic, environmental, and neuroscience of ADHD; and topics relevant to the diagnosis and treatment of ADHD from adolescence to early and late adulthood.

Aims of the Conference

This meeting aims to raise the level of knowledge and expertise among health care professionals about adults with ADHD and provide a better understanding of the persistence of the disorder, the development of comorbid mental health problems and the delivery of effective treatments. The program will be delivered by prominent opinion leaders, clinical experts and internationally recognised investigators.

Speakers

The selection of speakers is important so that the audience can hear directly from the most experienced professionals working in this rapidly developing area of clinical psychiatry.

Speakers will include : David Nutt, Eric tayor, Anita Thapar, Alexandra Philipsen, Ian Wong, Samuele Cortese,  Philip Shaw, Jessica Agnew-Blais and Pravina Rudra.

Welcome Reception – Art with Heart

There will be a welcome reception hosted by UKAAN on the evening of Thursday 12th September. This will be preceded by a Performance of ‘Declaration’ by Art with Heart. Developed in consultation with medical professionals, ADHD and mental health support groups, ‘Declaration’ examines when we want, need or are forced to declare our differences, and the faces we wear to fit in. Numbers are limited, so early booking is advised! 

Click here to register and for further details.

 

 

Pay Attention to ADHD – Podcast with prof. Stephen Faraone

Professor Stephen Faraone – professor in Psychiatry at SUNY Upstate University and expert on ADHD – was interviewed by dr. Therese Markow for the podcast series ‘Critically Speaking’. In this podcast they discuss myths about ADHD and the scientific evidence that debunks these myths. Stephen Faraone explains why it is so important to diagnose and treat ADHD early. He also explains why ADHD is often undiagnosed in girls, and why sometimes adults are diagnosed with ADHD who have not sought treatment earlier in their life.

Critically Speaking is a podcasts series hosted by dr. Therese Markow who interviews experts to discuss in plain language complex issues that concern our health, society and planet.

You can listen to the podcast here: http://criticallyspeaking.libsyn.com/002-pay-attention-adhd-with-dr-stephen-faraone

 

ADHD and autism – similar or different disorders?

Have you ever thought that ADHD and autism could perhaps be the same disorder? – Or have you thought that they are way too different, two different planets in the psychiatric universe? Researchers do not agree on this. We know that both ADHD and autism are neurodevelopmental conditions with onset in childhood and that they share some common genetic factors, however, they appear with quite different phenotypical characteristics. We also know that people with ADHD or autism have an increased risk of getting other psychiatric disorders, so-called comorbidities, and smaller studies have shown that individuals with ADHD or autism get different psychiatric disorders, and at a different degree.

How can we utilize this knowledge about different psychiatric comorbidities between ADHD and autism? How can we get closer to an answer to this question; are ADHD and autism similar or different conditions? By using large datasets; unique population-based registries in Norway, we wanted to compare the pattern of psychiatric comorbidities in adults diagnosed with ADHD, autism or both disorders. In addition, we wanted to compare the pattern of genetic correlations between ADHD and autism for the same psychiatric traits, and for this, we exploited summary statistics from relevant genome-wide association studies.

In the registries, we identified 39,000 adults with ADHD, 7,500 adults with autism and 1,500 with both ADHD and autism. We compared these three groups with the remaining population of 1.6 million Norwegian adult inhabitants without either ADHD or autism. The psychiatric disorders we studied were anxiety, bipolar, depression, personality disorder, schizophrenia spectrum (schizophrenia) and substance use disorders (SUD).

Interestingly, we found different patterns of psychiatric comorbidities between ADHD and autism, overall and when stratified by sex (Fig.1). These patterns were also reflected in the genetic correlations, however, only two of the six traits showed a significant difference between ADHD and autism (Fig.2).

Figure 1 - Solberg et al. 2019
Figure 1. Prevalence ratios of psychiatric disorders in adults with ADHD, autism or both ADHD and autism, relative to the remaining population, by sex. As can be seen in the figure, schizophrenia is more frequent in autism or ADHD+autism than ADHD alone, while the reverse is true for substance use disorder. There are also significant differences in prevalence between men and women. Figure from Solberg et al. 2019, CC-BY-NC-ND.

Figure 2. Left: The pattern of prevalence ratios of psychiatric comorbidity in adults with ADHD or autism observed in this study (ADHD; n=38,636, autism; n=7,528). Right: genetic correlations (rg) calculated from genome wide association studies. Psychiatric conditions are highly prevalent in both ADHD and ASD, with schizophrenia being most prevalent in ASD and antisocial personality disorders in ADHD. Genetic correlations are also high with both disorders, with especially high correlations between ADHD and alcohol dependence, smoking behavior and anti-social behavoiur. Major depressive disorder has high genetic correlations with both ADHD and autism. Figure from Solberg et al. 2019, CC-BY-NC-ND.

The most marked differences were found for schizophrenia and SUD. Schizophrenia was more common in adults with autism, and SUD more common in adults with ADHD. Associations with anxiety, bipolar and personality disorders were strongest in adults with both ADHD and autism, indicating that this group of adults suffers from more severe impairments than those with ADHD or autism only. The sex differences in risk of psychiatric comorbidities were also different among adults with ADHD and ASD.

In conclusion, our study provides robust and representative estimates of differences in psychiatric comorbidities between adults diagnosed with ADHD, autism or both ADHD and autism. With the results from analyses of genetic correlations, this finding contributes to our understanding of these disorders as being distinct neurodevelopmental disorders with partly shared common genetic factors.

Clinicians should be aware of the overall high level of comorbidity in adults with ADHD, autism or both ADHD and autism, and the distinct patterns of psychiatric comorbidities to detect these conditions and offer early treatment. It is also important to take into account the observed sex differences. The distinct comorbidity patterns may further provide information to etiologic research on biological mechanisms underlying the pathophysiology of these neurodevelopmental disorders.

This study was done at Stiftelsen Kristian Gerhard Jebsen Centre for Neuropsychiatric disorders, University of Bergen, Norway, and published OnlineOpen in Biological Psychiatry, April 2019, with the title:

“Patterns of psychiatric comorbidity and genetic correlations provide new insights into differences between attention-deficit/hyperactivity disorder and autism spectrum disorder”. https://doi.org/10.1016/j.biopsych.2019.04.021

Figure 1 and 2 are re-printed by permission https://creativecommons.org/licenses/by-nc-nd/4.0/

Berit Skretting Solberg is a PhD-candidate at the Department of Biomedicine/Department of Global Health and Primary Care, University of Bergen, Norway. She is also a child- and adolescent psychiatrist/adult psychiatrist. She is affiliated with the CoCa-project, studying psychiatric comorbidities in adults with ADHD or autism, using unique population-based registries in Norway.

 

Who is the average patient with ADHD?

Is there an ‘average ADHD brain’? Our research group (from the Radboudumc in Nijmegen) shows that the average patient with ADHD does not exist biologically. These findings were recently published in the journal. Psychological Medicine.

Most biological psychiatry research heavily relies on so-called case-control comparisons. In this approach a group of patients with for instance ADHD is compared against a group of healthy individuals on a number of biological variables. If significant group effects are observed those are related to for instance the diagnosis ADHD. This often results in statements such as individuals with ADHD show differences in certain brain structures. While our results are in line with those earlier detected group effects, we clearly show that a simple comparison of these effects disguises individual differences between patients with the same mental disorder.

Modelling individual brains

In order to show this, we developed a technique called ‘normative modelling’ which allows us to map the brain of each individual patient against typical development. In this way we can see that individual differences in brain structure across individuals with ADHD are far greater than previously anticipated. In future, we hope that this approach provides important insights and sound evidence for an individualized approach to mental healthcare for ADHD and other mental disorders.

Individual differences in ADHD

When we studied the brain scans of individual patients, the differences between those were substantial. Only a few identical abnormalities in the brain occurred in more than two percent of patients. Marquand: “The brains of individuals with ADHD deviate so much from the average that the average has little to say about what might be occurring in the brain of an individual.”

Personalized diagnosis of ADHD

The research shows that almost every patient with ADHD has her or his own biological profile. The current method of making a diagnosis of psychiatric disorders based on symptoms is therefore not sufficient, the authors say: “Variation between patients is reflected in the brain, but despite this enormous variation all these people get the same diagnosis. Thus, we cannot achieve a better understanding of the biology behind ADHD by studying the average patient. We need to understand for each individual what the causes of a disorder may be. Insights based on research at group level say little about the individual patient.”

Re-conceptualize mental disorders

The researchers want to make a fingerprint of individual brains on the basis of differences in relation to the healthy range. Wolfers: “Psychiatrists and psychologists know very well that each patient is an individual with her or his own tale, history and biology. Nevertheless, we use diagnostic models that largely ignore these differences. Here, we raise this issue by showing that the average patient has limited informative value and by including biological, symptomatic and demographic information into our models. In future we hope that this kinds of models will help us to re-conceptualize mental disorders such as ADHD.”

Further reading

Wolfers, T., Beckmann, C.F., Hoogman, M., Buitelaar, J.K., Franke, B., Marquand, A.F. (2019). Individual differences v. the average patient: mapping the heterogeneity in ADHD using normative models. Psychological Medicine, https://doi.org/10.1017/S0033291719000084 .

This blog was written by Thomas Wolfers and Andre Marquand from the Radboudumc and Donders Institute for Brain, Cognition and Behaviour in Nijmegen, The Netherlands. On 15 March 2019 Thomas Wolfers will defend his doctoral thesis entitled ‘Towards precision medicine in psychiatry’ at the Radboud university in Nijmegen. You can find his thesis at http://www.thomaswolfers.com

Researchers have found the first risk genes for ADHD

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 iPSYCH 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 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.

We study used genomewide 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 ADHD vs. 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:

  1. 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.
  2. B) we found a significant polygenic etiology in our data, which means that there must be many loci (perhaps thousands) having variants that increase 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 tell us that many of the genetic variants which increase the risk for ADHD also make it more likely that persons 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.

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.