What have we learned about ADHD comorbidities?

Posted on by Jeanette Mostert

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

Common mental health symptoms in ADHD

Posted on by Jeanette Mostert
Image by Anastasia Gepp from Pixabay
Excessive, uncontrolled mind-wandering is common to ADHD, but also to other mental health conditions. Mobile apps that prompt questions during the day can give more insight into the nature of these symptoms and how they differ between (often comorbid) conditions.

The majority of individuals with ADHD have one or more comorbid disorders. Comorbidity is a technical (and admittedly, not very cheerful) word for ‘co-occuring’, meaning that multiple disorders or conditions are present at the same time. Anxiety and depression are the most prevalent conditions that co-occur with ADHD.

Researchers and clinicians want to better understand this comorbidity in ADHD. Does having ADHD increase your risk of developing other conditions? Is there a biolgical mechanism that underlies both ADHD and other conditions? Or are symptoms of ADHD actually broader than the attentional, hyperactivity and impulsivity problems defined by the DSM/ICD, and therefore also linked to other conditions? Or all of the above?

Going with the third option (which by no means excludes the alternatives), clinicians have noticed that many individuals with ADHD experience symptoms that are not specific to ADHD, but are also often seen in other psychiatric conditions. You could call these symptoms ‘mainstream’, or ‘common’ mental health problems. Some examples that are often experienced by those with ADHD are emotional instability, sleep problems, low self-esteem, distractibility and concentration problems, and mental restlesnesss or excessive mind wandering.

Understanding these comorbidities better is important, because often one condition can hide the ‘true’ underlying condition. For instance, a person with ADHD who experiences many symptoms that are also characteristic of anxiety (i.e. low self-esteem, excessive mind-wandering, sleep problems, avoiding difficult situations). In such a case, the person could receive treatment for anxiety problems, while he or she is actually needing treatment for ADHD.

To distinguish between these conditions better, we need to find out more about these common symptoms. Being distracted can have many different causes and can happen in many different situations. For instance: are you distracted due to pervasive negative thoughts, because the task you’re doing is boring, or because you’re thinking of many related things and drift off to new ideas?

To learn more about the nature of these symptoms, researchers have given mobile apps or smartwatches to participants with ADHD. Several times a day, the watch buzzes and the app prompts a question that the person has to give answer to immediately. Questions can for instance be: How are you feeling right now? Have good/bad things happend to you in the last hour? How much has this affectd you? Were you concentrating on a task or where you distracted? Where you tinking about something (un)pleasant? etc. This method called ‘experience sampling’ can give very valuable information about someone’s symptoms. When combining the information from a lot of individuals, this can also identify differences between different disorders, that were not really known before.

If you want to learn more about this topic, you can watch this webinar by professor Philip Asherson from King’s College London. He explains the common mental health symptoms of ADHD in more detail, and gives examples from his research, also using experience sampling.

This blog is based on the webinar by Philip Asherson “ADHD in the mainstream” that was created as part of the CoCA project. The CoCA project investigates comorbid conditons of ADHD: .

Webinar: Does physical activity improve ADHD symptoms?

Posted on by Jeanette Mostert

There is a lot of anecdotal evidence that physical activity reduces ADHD symptoms. Some athletes, like Michael Phelps and Louis Smith, have said that their intenstive training helped them loose excessive energy and gain structure in their lives. But what is the scientific evidence for this?

Researcher dr. Jonna Kuntsi and her team from King’s College London have done a lot of reserach on this topic. They have reviewed the available literature on physical activitiy and ADHD, conducted analyses on twin-data and are conducting several experiments to test this. In this webinar she explains what’s known and what’s not yet known about whether physcial activity can improve ADHD symptoms

We previously wrote blogs about this topic as well:

Beneficial effects of high-intensity exercise on the attentive brain

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

CoCA-PROUD trial ready to roll

How psychiatric genetics can help to guide diagnostic practice and therapy

Posted on by Jeanette Mostert

Recently, professor Stephen Faraone from SUNY Upstate University in the USA gave a webinar about genetic research in psychiatry (especially ADHD) and how this can help to better understand diagnosis and provide better treatment. In this blog I will share with you some highlights from this webinar.

  1. ADHD is a continuous trait in the population

ADHD is not something that you either have or don’t have. Rather, symptoms or characteristics of ADHD are present in the entire population, in varying severity. The system for psychiatric diagnoses is however based on categorical definitions that determine when a certain combination of symptoms and severity can be classified as a particular disorder. Although these categories can be of great help to provide public health data or determine insurance coverage, they often don’t really match individual cases. Hence there arise problems with heterogeneity, subtypes, subthreshold cases and comorbidity.

Genetic research has shown that psychiatric conditions such as ADHD are not caused by a few single genes, but rather by thousands or tens of thousands genetic variants that each contribute slightly to the ADHD risk. These so-called polygenic risk scores form a normal distribution across the entire population, with the majority of people having low polygenic risk scores (so a low to average risk of ADHD), while a small portion of individuals have a very low or very high risk. This adds to our understanding that ADHD is a continuous trait in the population.

Image from the webinar by prof. Stephen Faraone. The higher the number on the x-axis, the higher the genetic risk of having ADHD. Negative numbers mean reduced genetic risk of ADHD.

2. Comorbidity in psychiatry is the norm, rather than the exception

In the webinar, Stephen Faraone explains that in 90’s it was thought impossible that an individual can have both ADHD and depression. Now, we know better than that. There are substantial genetic correlations between different psychiatric disorders, meaning that the genes that increase the risk of for instance ADHD, also increase the risk of schizophrenia, depression, bipolar disorder, autism and tic disorder. This is further evidence that psychiatric conditions are not separate, categorial entities but rather arise from similar biological mechanisms.

3. Personalised medicine and pharmacogenetics are not yet sufficiently established to adopt widely and replace current medication on a broad scale

The second part of the webinar was about pharmacogenetic testing. This means that an individual’s genetic profile is used to determine whether a drug will be effective, and in what dose. Although this sounds promising, there is still a lot of discussion about the validity of such tests. This is due to varying results, differing protocols and large heterogeneity between studies. In some cases, pharmacogenetic testing can help to find the right treatment for an individual, for instance when this person is not responding well to regular treatment, but it is definitely not a fool-proof method yet. Better randomized controlled clinical trials are needed to improve reliability of these tests.

You can watch the full webinar here: https://www.youtube.com/watch?v=DLgqdJWZKIo

The genetics of having multiple mental health conditions

Posted on by Jeanette Mostert

We know that psychiatric conditions have a strong genetic component. This means that genes play an important role in determining an individual’s risk or vulnerability to develop a psychiatric condition. However, there is evidence that there are genetic variants that increase the risk for multiple psychiatric disorders. This is called pleiotropy. Researchers of the “Cross-Disorder Group of the Psychiatric Genomics Consortium” have searched the entire genome of 727,000 individuals (of whom 233,000 were diagnosed with a psychiatric disorder) to identify genetic variants with such pleiotropy.

The researchers found one particular gene – called DCC – that increases vulnerability for all eight disorders that were investigated: ADHD, autism spectrum disorder, anorexia nervosa, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia and Tourette syndrome.

They also found more than 100 genetic variants that predispose to at least two psychiatric disorders, and around 20 variants that are associated with four or more. This means that the genes that contain these variants can be interesting to further understand why certain individuals are more vulnerable to develop psychiatric illnesses than others.

One of the researchers, professor Bru Cormand, explains more about this research in this blog.

Further reading: Cross-Disorder Group of the Psychiatric Genomics Consortium (2019): Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell, 179(7): 1469-1482.e11. 

Professor Cormand is involved in the CoCA research consortium where he investigates the genetic overlap between ADHD, major depression, anxiety disorder, substance use disorder and obesity. To read more about this, see for instance this other blog by him and dr. Judit Cabana Dominguez.

The genetic architecture of the brain

Posted on by Jeanette Mostert

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:

 

 

 

Prevalence and cost of ADHD comorbidity

Posted on by Jeanette Mostert

Do individuals with ADHD more often suffer from depression, anxiety, substance abuse or severe obesity, than individuals without ADHD? Are there differences between men and women in how often this is the case? Does having ADHD in addition to one of these conditions result in higher health care costs?

The short answers to these questions, are yes, yes and yes. In the CoCA-project, researchers have investigated these questions using very large datasets including Scandinavian birth registries that contain information of millions of people. This allows us to get a better understanding of how often conditions occor, how often they occur together, and how often they occur in men vs women. Furthermore, we have investigated health insurance data from Germany to study patterns of health care costs associated with ADHD and its comorbid conditions.

The interpretation of these data is however not simple. That is why we have recorded a webinar with dr. Catharina Hartman from Groningen, The Netherlands. She is the leader of these studies and can explain what these findings can and cannot tell us. The webinar ends with implications for policy makers and health care professionals, based on these findings.

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

Posted on by Jeanette Mostert

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. 

 

From genes to driving schools: an Estonian program to reduce traffic accidents

Posted on by Jeanette Mostert
Image by Netto Figueiredo from Pixabay

Driving is dangerous. 1.35 million people die from road accidents every year, according to the World Health Organization [1]. Young people who just obtained their driving license, and especially young men,  are at the highest risk for accidents. They are often seeking sensation, are more likely to take risks, and are more prone to take impulsive or thoughtless decisions while driving. To target this specific group, Estonian researchers have developed a training program for driving schools to make people aware of their impulsive tendencies.

Genetic predictors of traffic accidents

Interestingly, this Estonian research group that is led by professor Jaanus Harro specializes in genetics. Next to studying rats, Harro wanted to also investigate impulsive and aggressive behavior in humans. To measure this objectively outside of a laboratory setting they used data on traffic offences and accidents. Harro and his group found that a particular variation in the gene called 5-HTTLPR was associated with the number of speeding offences and traffic accidents [2]. People who have the short version of this variant are less likely to be caught for speeding or be involved in accidents, compared to those with the long variant.

The gene 5-HTTLPR is an important player in the serotonin system in the brain. Serotonin is a messenger molecule with many functions, one of them being the regulation of mood, impulsivity and aggression. Some people are more prone to act without thinking, or without considering the consequences, and this can partly be explained by genetics.

Reducing impulsive driving behavior

So should only people with the short version of 5-HTTLPR be allowed to drive? No, Harro and his team came up with something better: a program to reduce impulsive behavior on the road. They gave this to students who were learning to drive. In the training, students discussed their own impulsive tendencies, and ways to overcome these tendencies. There was also a control group that did not receive this extra lesson. Four years after obtaining their licenses, the group that received the training had been less involved in traffic violations and accidents than the control group. What’s more, those individuals with the long variant of 5-HTTLPR – so the ones who are more likely to be impulsive, based on this gene – benefited from the training the most.

For the driving schools the main implication of this experiment is that it is very beneficial to incorporate awareness training about impulsivity into driving lessons. Already eight driving schools in Estonia are providing the program to their students. The genetic findings however are mainly of interest to the researchers, who are hoping to gain a better understanding of impulsive and aggressive behavior. In addition to the serotonin-gene, they have found that genetic variations in the noradrenaline and dopamine system are also linked to traffic offenses and speeding, and to the effectiveness of the training [3, 4]. And just recently, they found that the neuropeptide orexin is linked to both aggression and to the prevalence of drunk driving and traffic accidents [5].

Beyond genetics

In addition to genes, other factors such as age, intelligence, and stressful life events influence the risk of offences and accidents as well, but we still know very little about how this works. That is why Harro and his team are now investigating the interactions between genes and environment. This research is part of the horizon2020 projects CoCA and Eat2beNICE. Ultimately, through a better understanding of our biology they hope to improve the way that people behave on the road, thereby reducing the number of accidents.

Meanwhile, Jaanus Harro travels to ministries and other governmental organizations in Estonia and Finland, to convince them to implement the training program on a national level, and to provide funds for further research. And in case you wonder about Harro’s own driving habits: although he acknowledges that he is quite impulsive, he assures us that he has learned to keep this under control while driving.

Jaanus Harro was recently interviewed by Science Business about this topic. Parts of this blogpost ar based on this interview. You can read the article here: https://sciencebusiness.net/keeping-drivers-impulses-check

References

[1] https://www.who.int/news-room/fact-sheets/detail/road-traffic-injuries (accessed 3 January 2020).

[2] Eensoo, Paaver, Vaht, Loit & Harro (2018). Risky driving and the persistent effect of a randomized intervention focusing on impulsivity: The role of the serotonin transporter promoter polymorphism. Accident Analysis and Prevention, 113, 19-24. https://www.ncbi.nlm.nih.gov/pubmed/29407665

[3] Paaver, Eenso, Kaasik, Vaht, Mäestu & Harro (2013). Preventing risky driving: A novel and efficient brief intervention focusing on acknowledgement of personal risk factors. Accident Analysis and Prevention, 50, 430-437. https://www.ncbi.nlm.nih.gov/pubmed/22694918

[4] Luht, Tokko, Eensoo, Vaht & Harro (2019). Efficacy of intervention at traffic schools reducing impulsive action, and association with candidate gene variants. Acta Neuropsychiatrica, 31, 159 – 166. https://www.ncbi.nlm.nih.gov/pubmed/31182183

[5] Harro, Laas, Eensoo, Kurrikoff, Sakala, Vaht, Parik, Maëstu & Veidebaum (2019). Orexin/hypocretin receptor gene (HCRTR1) variation is associated with aggressive behaviour. Neuropharmacology, 156. https://www.ncbi.nlm.nih.gov/pubmed/30742846

 

Mythbusters: artificial food colours and ADHD

Posted on by Jeanette Mostert

When I was a kid, there was a boy in my class called Jeroen. At times I found him friendly and funny, but other times he would drive me insane with his hyperactive behaviour, jumping around and pulling my hair. Then one day, he told us that we wasn’t aloud to eat anything with artificial food colours anymore. This was supposed to reduce his hyperactivity. I was hopeful, but also sceptical if this would work.

Now that I’m involved in an international consortium investigating food and behaviour, I finally had the chance to learn about food colours and ADHD. Turns out, there is some truth to the claim, although it may only be true for some children, and it may not be specific to ADHD.

A shitty story

To better understand the effects of food on behaviour, we need to start at the end. Your poo can actually tell us a lot about the billions of microbes that live in your gut and help to digest the food you eat. For a long time, we didn’t know much about this micro-wildlife, until scientists developed techniques to analyse large amounts of DNA very quickly and cheaply. As every species has unique DNA, researchers can identify all the different species that live in your gut by analysing their DNA from poo. This helps us to better understand the many important roles that the gut bacteria play in your body, including your brain. For instance, certain bacteria produce neurotransmitters from digesting fibres. These neurotransmitters are important for the communication between brain cells.

ADHD

What does this have to do with ADHD? ADHD is a neurodevelopmental condition, which means that the brain develops differently compared to typically developing children. This influences the functioning of the brain and hence people with ADHD have problems focussing their attention, controlling their impulses and regulating their activity. A disruption in the neurotransmitter system is thought to play a key role in this. While the main cause of ADHD is genetic, environmental factors are also known to increase the risk of the condition, such as smoking during pregnancy, toxins in the environment, and food allergies. Since recently, researchers are investigating the gut bacteria (aka the poo) to better understand how food allergies may trigger ADHD [1].

Food allergies

The microbes in the gut interact closely with the immune system. During development the immune system has to learn that many foreign substances in the intestines (i.e. food and bacteria) are good and should not be attacked. In a way, it has to learn not to overreact. And this is what happens with food allergies. The over-reaction of the immune system is harmful for both the gut environment and for the brain, especially if it happens very often. Hence, an allergic reaction to food colourings may trigger small changes in the brain that in turn may trigger behaviour such as hyperactivity. How this works exactly is still unknown.

Based on this theory, clinicians and nutritionists are now investigating if special diets can reduce ADHD symptoms [2]. In such a diet, a child is put on a very restrictive diet that eliminates any potentially allergenic substances. To see which food types trigger the symptoms, specific foods are introduced one by one. For some children, this really seems to work well and they can manage their symptoms by not eating certain foods the rest of their lives. The elegance of this method is that it is based on the individual. While one person may need to eliminate food colourings, for another it could be certain fruits, or cow’s milk.

Myth busted?

Do artificial food colours cause ADHD? This may be the case for some children. In others, other types of food may trigger ADHD symptoms. And in yet another group of children, their ADHD has nothing to do with food allergies. At the moment, the only way to find out is through trial and error. But only try this under supervision of trained nutritionists and clinicians!

Back to Jeroen. I don’t remember him getting less annoying. Perhaps he was not allergic to food colourings at all, and he should have tried the complete elimination diet or different medication. Or perhaps I was just an eight-year old girl allergic to all boys.

References

  1. Dam, S. et al. (2019) The Role of the Gut-Brain Axis in Attention-Deficit/Hyperactivity Disorder. Gastroenterol Clin N Am, 48, 407–431
  2. Ly, V. et al. (2017) Elimination diets’ efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. European Child and Adolescent Psychiatry, 26, 1067-1079.

This blog was written by dr. Jeanette Mostert. She is a neuroscientist and science communicator. She is involved in the CoCA-project and Eat2beNICE project. In the latter she is learning all about the links between food and mental health.