Prevalence and cost of ADHD comorbidity

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

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

 

Cocaine dependence is in part genetic, and it shares genetic risk factors with other psychiatric conditions and personality traits.

Cocaine is one of the most used illicit drugs worldwide and its abuse produces serious health problems. In Europe, around 5.2% of adults (from 15 to 64 years old) have tried cocaine, but only 20% will develop addiction. Why? Genetics is part of the answer. Cocaine dependence is a complex psychiatric disorder that results from the interaction of both environmental and genetic risk factors. Twin and adoption studies indicate that genetic alterations contribute substantially to cocaine dependence susceptibility, which has an estimated genetic load (heritability) as high as 65-79%. Although many studies with focus on candidate genes have been performed, only a few risk variants for cocaine dependence have been identified and replicated so far.

https://www.
flickr.com/photos/30478819@N08/24042216187

In this study we performed a meta-analysis of genome-wide association studies (GWAS) of cocaine dependence using more than 6,000 European ancestry individuals. This approach allowed us to inspect a huge number of genetic variants distributed all along the genome that are common in the general population. We identified a gene (HIST1H2BD) associated with cocaine dependence that is located in a region on chromosome 6 enriched in genes that encode histones, proteins that combine with DNA, protecting it and contributing to the activation (or inhibition) of genes. Some of these genes have previously been associated with schizophrenia.

Several studies have shown that substance use disorders (SUD), and especially cocaine dependence, co-occur in patients with other psychiatric disorders and personality traits. Such comorbidity is associated with increased severity for all disorders, although it is unclear whether this relationship is causal or the result of shared genetic and/or environmental risk factors. We calculated the shared genetics (genetic correlation) between cocaine dependence and six comorbid conditions. For the first time we found significant genetic correlation with attention deficit/hyperactivity disorder (ADHD), schizophrenia, major depression and risk- taking behavior. We also used another approach (polygenic risk score analysis, PRS) to prove that all tested comorbid conditions are associated with cocaine dependence status, suggesting that cocaine dependence is more likely in individuals that carry genetic risk factors for the tested conditions than in those that do not.

To our knowledge, this is the largest reported GWAS meta-analysis in European-ancestry individuals with cocaine dependence. We identified suggestive risk factors for the disorder in several genomic regions and found evidence for shared genetic risk factors between cocaine dependence and several co-occurring psychiatric traits. However, the size of the sample is still limited and further studies are needed to confirm our results.

Read more at: https://www.sciencedirect.com/science/article/pii/S0278584619301101?via%3Dihub

Judit Cabana-Domínguez and Bru Cormand

Judit Cabana Domínguez is a Postdoctoral researcher at the Genetics, Microbiology and Statistics Department at the University of Barcelona.

Bru Cormand is Full Professor of Genetics at the Genetics, Microbiology and Statistics Department at the University of Barcelona.

Light therapy and its influence on ADHD: An interview

 

Nina (27 years, Dutch) participated in the PROUD-study and followed our light therapy. In this interview she describes the influences light therapy had on her ADHD symptoms.

What is it like to live with ADHD?

Please describe your main symptoms.

The symptom I experience as the most troublesome is making new friends. It is harder for me to make new friends, knowing I have fewer emotional and cognitive skills than peers. I am more sensitive to persons and situations and I experience them as more severe.

Besides, it is harder for me to see things in perspective and my perspectives change a lot over short periods of time. This makes it harder to look further in the future when making decisions. I also have less patience and it is harder for me to concentrate on a task. 

How does ADHD influence your life?

As I explained in the question before it can be tough to make friends. Concerning work, my ADHD has positive and negative effects. The negative effects are my lack of concentration, sometimes a job has to be done at a certain moment when I have no concentration, which can be a real struggle. The positive side is that I am creative and my spatial development is good. These are qualities that come handy at my job. Also my intelligence helps me. Because I am smart I can work fast at the moments my concentration is good, in order to compensate for the moments where my concentration is lost.

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

It sure has, but these influences often last for a short period of time. I can be really enthusiastic and I am good at identifying people. This quality makes me a really good friend. Also my creativity is a positive effect of ADHD.

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

For a year and a half I have lived internally in a group especially for adolescents with ADHD and/or autism. Here I followed a training to improve my social abilities, how to engage in relationships with others and to be more independent.

From my 16th I take medication. I have switched a lot and tried different kinds of medication. Much of them did not work well for me, I even tried anti-depressants which made me feel sad. I am currently taking Stratera (short acting) and this works well for me. I don’t take it regularly but only at moments where I think I need it.

Study and intervention

How did you learn about the study?

I am regularly searching the internet to learn more about ADHD. This time I was searching information about comorbidity and neurodiversity and this is how I found your website, by chance.

What motivated you to participate?

It is a good thing that more research is done and I find it important to contribute. The more research is being conducted, the better others with ADHD can be helped. It is of great importance of me to be able to be a part in this. As long as we do not contribute to this kind of research, nothing will chance.

What were your expectations about the study before you started?

To be honest I did not have any expectations because I did not want to be affected by them.

What intervention did you participate in? When?

I participated in the bright light therapy from the 18th of October (2018) until the 10th of January (2019).

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

At the beginning it was kind of hard, I found it really hard to be sitting still half an hour in the morning. Normally I rush through the mornings and do not really sit still at all. My solution was to put the lamp at my nightstand and sit in bed for half an hour in the morning, waking up next to the lamp. You can adjust the brightness of the lamp so I started with dimmed light and increased brightness step by step. Important is to sit upright because otherwise there is a chance of falling back to sleep!

In the beginning I had not realized what an impact this therapy has on your daily life, you really need the motivation to sit through, every day. After some time I got adapted to a new rhythm which made it easier to follow the light therapy for 6 times week. Only on Saturdays I skipped the sessions because of the weekend.

Was the intervention helpful?

It definitely has positive influences. The biggest change I have experienced is the adaptation to a more natural day/night rhythm. I was hoping a side effect would be falling asleep faster but unfortunately this was not the case for me.

The first days I experienced some negative side effects, which are explained in the bright light manual. Maybe it would be better if I had not read the manual because I was so focused on the experience of these side effects. What I felt was a really grumpy mood in the mornings. Luckily it only lasted for a few days.

Are you planning on continuing the intervention?

No, I have no plans of buying a lamp myself. Looking back at the intervention I think I would benefit more by participating in the aerobic exercise intervention, because sitting still for half an hour without a clear purpose is tough. Of course I did adapt to a better and more natural day/night rhythm because of the bright light therapy, but I think this could also be accomplished by going to bed at the same time every day.

Was it difficult/easy to use the App?

Definitely not difficult. The researches informed me about the sensor and how it might be inconvenient in the beginning but I only had to get used to it during the nights. The app was really clear and straight-forward, easy to use. I did forget the phone a few times, making me drive back home, but if you wear pants with pockets this should not be a problem.

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

I would definitely recommend it to people who are interested in this study and are motivated to participate. You really have to do it because you want it, not only because you want to help others.

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

In my experience the study is set up well. Sometimes something went wrong (system was not installed right so they had to send me a new set, this set came without a wristband, red.) but the researchers handled it well and professionally. The researchers were cooperative and I liked participating in this study.

Lisa Bos, MSC works at Karakter Child and Youth Psychiatry and Radboud UMC (Nijmegen, the Netherlands) where she works as a researcher for the TRACE project and the PROUD-study. Both studies focus on additional treatments for ADHD and a healthy lifestyle which are also her main interests. She finds importance in studying socially relevant topics and improving the quality of care for ADHD patients.

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.

 

Epigenetic signature for attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is considered a complex disorder caused by underlying genetic and environmental risk factors. To make it even more complex, environmental factors can influence the expression of genes. This is called epigenetics.

Given the large proportion of the heritability of ADHD still to be explained, there is a growing interest in the epigenetic mechanisms that modulate gene expression. microRNAs (miRNA) are small parts in the human genome that do not code for genes, but instead regulate the expression of other genes by promoting the degradation or suppressing the translation of those target genes. miRNA therefore provide a means to integrate effects of genetic and environmental risk factors.

The human genome encodes more than 2500 different miRNAs, the majority of which are expressed in the brain. miRNAs are known to be involved in the development of the central nervous system and in many neurological processes including synaptic plasticity and synaptogenesis. Given the limited accessibility of the human brain for studying epigenetic modifications, miRNA profiling in peripheral blood cells is often used as a non-invasive proxy to study transcriptional and epigenetic biosignatures, and to identify potential clinical biomarkers for psychiatric disorders.

We recently investigated the role of microRNAs in ADHD at a molecular level, by conducting the first genome-wide integrative study of microRNA and gene expression profiles in blood of individuals with ADHD and healthy controls. We identified three miRNAs (miR-26b-5p, miR-185-5p and miR-191-5p) that have different expression levels in people with ADHD, compared to those without ADHD. When we investigated downstream miRNA-mediated mechanisms underlying the disorder this provided evidence that aberrant expression profile of these three miRNA may underlie changes in the expression of genes related with myo-inositol signaling. This mediates the biological response of a large number of hormones and neurotransmitters on target cells. We also found that these miRNAs specifically targeted genes involved in neurological disease and psychological disorders.

These findings show that epigenetic modifications through microRNAs play a role in ADHD, and provide novel insights into how these miRNA-mediated mechanisms contribute to the disorder. In the future, these miRNAs may be used as peripheral biomarkers that can be easily detected from blood, as is shown in the figure.

What´s next?

The mechanism through which miRNAs modify gene expression is complex and dynamic. Therefore, future studies are required to provide deeper insights into the epigenetic mechanisms underlying ADHD, and to identify specific molecular networks that may be crucial in the development of the disorder.

Further reading

Cristina Sánchez-Mora et al. Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells, Neuropsychopharmacology, volume 44, pages 890–897 (2019).

https://www.nature.com/articles/s41386-018-0297-0

About the author

Cristina Sánchez-Mora is postdoctoral researcher at the Psychiatry, Mental Health and Addictions group at Vall d’Hebron Institut de Recerca (VHIR). Her research is part of the CoCA consortium that investigates comorbid conditions of ADHD