IMpACTnextgen: the next generation of IMpACT researchers

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Near the beautiful castle in Örebro, Sweden 2018, we kicked off our new network of enthusiastic researchers working in the ADHD research field. This network consists of early and mid-career researchers who work on topics related to ADHD across the lifespan and have a link with one of the IMpACT (International Multicenter persistent ADHD CollaboraTion) projects.

Our network has the aim to unite the knowledge of the individual young researchers in the field of ADHD to boost the further development of our field. Furthermore, we aim to facilitate the exchange of students and offer them international experiences in our research labs. Our final aim is to have closer ties between the members. This way it will become easier to replicate research findings, collaborate and brainstorm with researchers that work on related topics.

In Frankfurt 2019 we decided to start working towards a first collaborative project. More about this will follow soon.

Our work can be followed here on ‘mind-the-gap.live’ by our tag ‘impactnextgen’

 

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If you want to join or have ideas, please contact any of us, or contact Martine Hoogman martine.hoogman@radboudumc.nl (chair)

 

The cortex and ADHD: the second project of the ENIGMA-ADHD collaboration.

After the first project on subcortical brain volumes in ADHD, published in Lancet Psychiatry in 2017 , ENIGMA-ADHD now analysed cortical data of 2246 people with a diagnosis of ADHD and 1713 people without, aged between four and 63 years old.  The data came from 37 research groups from around the world. FreeSurfer (imaging software) parcellations of thickness and surface area of 34 cortical regions were compared between cases and controls in 3 separate age groups; children, adolescents and adults.

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Subtle differences only in the group of children were found. The childhood effects were most prominent and widespread for the surface area of the cortex. More focal changes were found for thickness of the cortex. All differences were subtle and detected only at a group level, and thus these brain images cannot be used to diagnose ADHD or guide its treatment.

These subtle differences in the brain’s cortex were not limited to people with the clinical diagnosis of ADHD: they were also present – in a less marked form – in youth with some ADHD symptoms. This second finding results from a collaboration between the ENIGMA-ADHD Working Group and the Generation-R study from Rotterdam, which has brain images on 2700 children aged 9-11 years from the general population. The researchers found more symptoms of inattention to be associated with a decrease in cortical surface area. In a third study, using the NeuroImage data from Nijmegen and Amsterdam, familial effects on those regions that showed case-control differences were investigated.  Siblings of those with ADHD showed changes to their cortical surface area that resembled their affected sibling. This suggests that familial factors such as genetics or shared environment may play a role in brain cortical characteristics.

We identified cortical differences that are consistently associated with ADHD combining data from many different research groups internationally. We find that the differences extend beyond narrowly-defined clinical diagnoses and are seen, in a less marked manner, in those with some ADHD symptoms and in unaffected siblings of people with ADHD. This finding supports the idea that the symptoms underlying ADHD may be a continuous trait in the population, which has already been reported by other behavioural and genetic studies.’ In the future, the ADHD Working Group, which is led by Martine Hoogman and Barbara Franke from the Radboudumc in Nijmegen, hopes to look at additional key features in the brain- such as the structural connections between brain areas – and to increase the representation of adults affected by ADHD, in whom limited research has been performed to date.

Link to the article: Hoogman et al., Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

To learn more about other projects that are carried out using ENIGMA-ADHD data, please also read the paper by Yanli Zhang-James and colleagues on bioRxiv. Here, the ENIGMA-ADHD data of the first and the second project were used to do prediction modelling.  

The ADHD Working Group is one of over 50 working groups of the ENIGMA Consortium, in which international researchers pull together to understand the brain alterations associated with different disorders and the role of genetic and environmental factors in those alterations. For more information about ENIGMA-ADHD please visit our website http://enigma.usc.edu/ongoing/enigma-adhd-working-group/ or contact Martine Hoogman martine.hoogman (at) radboudumc.nlenigma_300dpi

Is there a positive side to having ADHD?

If you are searching for positive aspects of ADHD on the web, you will find a lot of websites claiming all kinds of positive sides to having ADHD, such as being more creative, able to hyperfocus, or being more spontaneous. However, if you try to back up this information by scientific evidence, you will be disappointed. Up to now, research in ADHD has almost exclusively focused on cognitive and behavioral deficits in people with the disorder. With ADHD being a disabling disorder, this may not be surprising on the one side. On the other, however, scientific research in several other target groups, shows there is indeed evidence pointing in the direction of a positive side of neurodevelopmental disorders and traits associated with ADHD. Take for example creativity: for disorders such as bipolar disorder and schizophrenia, strong links with creativity have been observed in large samples1, and these disorders overlap phenotypically (e.g. through impulsivity) and genetically with ADHD. Also, creative people are often risk-takers and novelty seekers, as are people with ADHD20. From genetic studies, we can also derive suggestive evidence for a possible link between ADHD and creativity. groenebrainlampwebsiteMHThe dopamine receptor D4 gene (DRD4), also sometimes called the ‘adventure gene’, is a candidate ADHD risk gene identified by meta-analysis2 but has also been associated with increased divergent thinking3. Further evidence comes from brain imaging studies, showing brain regions involved in creative thinking, temporal and frontal lobe4, 5, to overlap regions implicated in ADHD (Hoogman et al. in prep & e.g.6).

What is already known about creativity and ADHD?

Creativity tests can be divided into tasks that measure divergent thinking (such as the alternative or unusual uses task and the Torrance test of creative thinking), and tasks that measure convergent thinking (e.g. the remote associations task). Also, questionnaires that relate to creative achievement are used to acquire information about ones creative abilities (e.g. the creative achievement questionnaire). A handful of studies has linked ADHD (symptoms) with creative performance. These studies had a maximum sample size of 90. Healey and colleagues showed that among creative children, ADHD symptoms were higher than in less creative children7. Another study, by White and Shah, found increased divergent thinking in ADHD college students as compared with non-ADHD college students8. And also higher creative achievement was found in ADHD9. Additional studies did not find a relationship between ADHD (symptoms) and creativity. For example, in a study by Aliabadi and colleagues, there was no difference on a figural Torrance test of creative thinking, and patients performed worse on fluency and flexibility11.

Another way of looking at potential links between creativity and ADHD is by using possible proxies of creativity, e.g. having a creative profession. Investigating the Swedish population registries in this way did not result in evidence for more creative professions among people with ADHD than among others12. This might be due to the categorization of creative professions (writers, painter, dancers, scientists), as this might be too broad. Also, people with ADHD are often unemployed, which would lead to an underrepresentation of people with ADHD in these studies.

So (what now)…?

Patients consistently claim a link between creativity in ADHD, but this link has not been the subject of large-scaled studies that are indispensable to define such a potential link scientifically. The one large, proxy-based study of creativity and ADHD, did not find a link between both12. Should we stop there? I don’t think so. Following the demand of patients to know more about creativity in ADHD as well as the promising findings of several small-sampled studies, I think that it does deserve our attention to not only focus on the deficits of ADHD. Finding answers on this subject might reduce stigma in ADHD, as we know from previous work that more knowledge about a disorder will create understanding and lessen prejudice13. In addition, it also has the potential to help patients cope with their disorder and support them in making choices education- and career-wise.

Therefore, we are currently making a first attempt to study creativity in our adult ADHD clinical study (IMPACT2-NL) by testing creative performance on divergent and convergent thinking tasks and by administering a creative achievement questionnaire. To be able to relate creative performance to the known cognitive deficits of ADHD, we will also assess those. In addition, we will also collect brain imaging and genetic data to gain knowledge on the underlying neural mechanisms. We are also working on reaching out to other ongoing studies to add creativity tasks to their testing batteries.

It goes without saying that ADHD is a debilitating disorder. However, we feel that if there is a chance that some positive sides of ADHD exist, they deserve to be studied.

 

Dr. Martine Hoogman, senior postdoc and PI of IMpACT2-NL

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References

  1. Thys, E., Sabbe, B. & De Hert, M. Creativity and psychopathology: a systematic review. Psychopathology 47, 141-147 (2014).
  2. Gizer, I., Ficks, C. & Waldman, I. Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 126, 51-90 (2009).
  3. Mayseless, N., Uzefovsky, F., Shalev, I., Ebstein, R.P. & Shamay-Tsoory, S.G. The association between creativity and 7R polymorphism in the dopamine receptor D4 gene (DRD4). Front Hum Neurosci 7, 502 (2013).
  4. Cousijn, J., Koolschijn, P.C., Zanolie, K., Kleibeuker, S.W. & Crone, E.A. The relation between gray matter morphology and divergent thinking in adolescents and young adults. PLoS One 9, e114619 (2014).
  5. Dietrich, A. & Kanso, R. A review of EEG, ERP, and neuroimaging studies of creativity and insight. Psychol Bull 136, 822-848 (2010).
  6. Shaw, P., et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci U S A 104, 19649-19654 (2007).
  7. Healey, D. & Rucklidge, J.J. An investigation into the relationship among ADHD symptomatology, creativity, and neuropsychological functioning in children. Child Neuropsychol 12, 421-438 (2006).
  8. White, H. & Shah, P. Uninhibited imaginations: Creativity in adults with Attention-Deficit/Hyperactivity Disorder. Personality and individual differences 40, 1121-1131 (2006).
  9. White, H.A. & Shah, P. Creative style and achievement in adults with attention-deficit/hyperactivity disorder. Personality and Individual Differences 50, 673-677 (2011).
  10. Healey, D. & Rucklidge, J.J. An exploration into the creative abilities of children with ADHD. J Atten Disord 8, 88-95 (2005).
  11. Aliabadi, B., Davari-Ashtiani, R., Khademi, M. & Arabgol, F. Comparison of Creativity between Children with and without Attention Deficit Hyperactivity Disorder: A Case-Control Study. Iran J Psychiatry 11, 99-103 (2016).
  12. Kyaga, S., et al. Mental illness, suicide and creativity: 40-year prospective total population study. J Psychiatr Res 47, 83-90 (2013).
  13. Mueller, A.K., Fuermaier, A.B., Koerts, J. & Tucha, L. Stigma in attention deficit hyperactivity disorder. Atten Defic Hyperact Disord 4, 101-114 (2012).

Subcortical brain volumes in ADHD: the ENIGMA ADHD study

Many neuroimaging studies in ADHD have been published, each with its own contribution to science. However, brain imaging studies are expensive and therefore the sample size of studies is often small, which could result in not finding effects that are actually there. Also, different methods are used, which makes it difficult to compare studies. This results in inconsistent findings and still many uncertainties about the neurobiology of ADHD. To address these issues we founded the ENIGMA-ADHD consortium. Here, many experts in the field are united to share their expertise and their data. This way we can reanalyze existing data in large meta-and mega-analyses to try to get as close as possible to finding true effects in the brain. Our first paper was published last week in The Lancet Psychiatry and received a lot of press.

Summary of the results

We studied volume differences of 7 subcortical brain regions in >1.700 people with and >1.500 without the ADHD diagnosis from 23 collaborating institutes, with and age range of 4-63 years. We found smaller volumes for the amygdala, areas in the striatum (accumbens, caudate nucleus and putamen) and the hippocampus. The effects were small, in the order of 1 %. The differences were most pronounced in children with ADHD, differences in adults were not significant. We also studied the effects of presence of co-morbid disorders and the use of stimulants, but no effects were found. Neither did we find a correlation between the severity of ADHD (number of symptoms) and the brain volumes. Our effects are similar in size when comparing them to other psychiatric disorders such as depression (1). Compared to previous meta-analysis on brain structure in ADHD, our amygdala, accumbens and hippocampus findings are new. The amygdala finding is interesting as this structure in the brain is involved in emotion regulation and connected with many other parts of the brain. Emotional regulation problems are often mentioned in ADHD, but have not been the subject of many studies yet.

What does it mean?

…or equally important, what does it not mean: it does not mean that we can diagnose patients based on their brain scan. Effects are small and we can only identify the differences if we study large groups of patients. Neither can we say anything about cause or consequence, which was not the aim of our study. Also we need to be cautious about interpreting the age findings as this was a cross-sectional study, longitudinal studies should confirm our results.

So what can we say about our results? We have been trying to understand what ADHD is for a long time now and we use multiple levels of research to find answers to our questions. We study behavior, cognition, genetics, environmental factors and also the structure and functioning of the brain. This results in pieces of the puzzle which together should make up the picture of ADHD. The results of our study contribute to a better characterization of the neurobiology underlying the disorder by showing the amygdala, the striatal regions and the hippocampus to be implicated in ADHD. Further research into the associations with for example behavior and also the meaning of the size of the effects should give us more information on what our results actually mean.

What next?

So far we only studied 7 brain regions, and next we want to focus on the thickness and surface area of the cortex. We are also setting up a DTI study within the framework of ENIGMA-ADHD. Our dataset is open to anyone who wants to work with the data and comes up with a good idea. Currently a handful of researchers are working on side projects such as making prediction models and using machine learning algorithms. Others study subparts of particular brain regions (cerebellum). In the meantime we keep growing as a working group, welcoming new institutes at any time. We have grown to 34 participating sites with data of over 4000 participants. We especially encourage cohorts with older ADHD participants, as coverage of this age range is limited in our dataset.

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For more information about ENIGMA-ADHD please visit our website http://enigma.usc.edu/ongoing/enigma-adhd-working-group/ or contact Martine Hoogman martine.hoogman (at) radboudumc.nl

 

  1. Schmaal L, Veltman DJ, van Erp TG, et al. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Mol Psychiatry. 2015.