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.
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.
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
- 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.