Subtle Differences in Brain Volume Detected On MRI In ADHD Interview with:
M. (Martine) Hoogman PhD.

Postdoc and PI of ENIGMA-ADHD
Radboud universitair medisch centrum
Department of Human Genetics
Nijmegen, The Netherlands What is the background for this study? What are the main findings?

Response: There are many neuro-imaging studies aimed at investigating structural brain changes related to ADHD, but the results are often inconclusive.

There are two main reasons for this:

1) the small sample size of the studies and
2) the heterogeneous methods used.

We tried to address these issues by forming an international collaboration to provide a sample size sufficient to detect even small effects in volume differences. And in addition, we analyzed all the raw scans again using homogenized methods. There are data of more than 1700 patients (aged 4-63 years of age) and more than 1500 healthy controls in our dataset, coming from 23 sites around the world. We studied the possible volume differences between cases and controls of 7 subcortical regions and intracranial volume by performing mega- and meta-analysis. What are the main findings?

Response: The main findings are that we found 5 subcortical brain volumes to be decreased in volume in patients with ADHD, as well as total intracranial volume. The differences were very small, in the order of 1 percent, but statistically significant. The largest effect was found in the amygdala, a region involved in emotional regulation and inhibitory control. These are behavioral aspects that can be linked to the ADHD phenotype. Also the effects were most pronounced in children with ADHD, the differences were not significant in adults with the disorder. We found no normalizing effects of stimulant use as was found before, nor were there any effects of the presence of co-morbid disorders or severity of the disorder. The differences in brain volume related to ADHD are similar in size and sometimes overlapping but also different in location when compared to other psychiatric disorders. What should readers take away from your report?

Response: We found small but significant differences when we looked at the average of subcortical brain volumes in a large group of ADHD patients. These results give better insights in the neural substrates underlying ADHD, as before the results were very inconclusive. This was not a study to assess the diagnostic value of an MRI scan and it is not possible to diagnose ADHD based on a brain scan. The important thing that should be taken from this study is that we found very subtle differences in the brains of a large group of people with ADHD, what this means on a behavioral level, or what causes it, should be studied in future studies. What recommendations do you have for future research as a result of this study?

Response: The presentation of ADHD is very heterogeneous; among patients different clinical presentations exist, and different cognitive profiles are displayed (and some don’t have cognitive deficits), also the causative mechanisms might vary among patients and likewise, there is much individual brain variation in patients with ADHD. Multiple approaches are needed to study ADHD, those that focus on the individual differences but also those that focus on the commonalities. We will follow the results of the current study up by looking at different parts of the brain (cortex, connectivity) to get a better picture on the neural substrates linked to those with an ADHD diagnosis and will use optimal methods (sufficient sample size and homogenous analysis) to assess these.

I personally have nothing to disclose but this is a collaborative of 81 researchers from 23 sites around the world, some with and some without disclosures (see the original paper). All data were treated equally and therefore the disclosures did not influenced the results. Thank you for your contribution to the community.


Lancet Psychiatry. 2017 Feb 16. pii: S2215-0366(17)30049-4. doi: 10.1016/S2215-0366(17)30049-4. [Epub ahead of print]
Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.
Hoogman M1, Bralten J2, Hibar DP3, Mennes M4, Zwiers MP4, Schweren LS5, van Hulzen KJ2, Medland SE6, Shumskaya E2, Jahanshad N3, Zeeuw P7, Szekely E8, Sudre G8, Wolfers T2, Onnink AM2, Dammers JT9, Mostert JC2, Vives-Gilabert Y10, Kohls G11, Oberwelland E12, Seitz J13, Schulte-Rüther M12, Ambrosino S7, Doyle AE14, Høvik MF15, Dramsdahl M16, Tamm L17, van Erp TG18, Dale A19, Schork A20, Conzelmann A21, Zierhut K22, Baur R23, McCarthy H24, Yoncheva YN25, Cubillo A26, Chantiluke K26, Mehta MA27, Paloyelis Y27, Hohmann S28, Baumeister S28, Bramati I29, Mattos P30, Tovar-Moll F31, Douglas P32, Banaschewski T28, Brandeis D33, Kuntsi J34, Asherson P34, Rubia K26, Kelly C35, Martino AD25, Milham MP36, Castellanos FX37, Frodl T38, Zentis M39, Lesch KP40, Reif A41, Pauli P23, Jernigan TL42, Haavik J43, Plessen KJ44, Lundervold AJ45, Hugdahl K46, Seidman LJ47, Biederman J48, Rommelse N49, Heslenfeld DJ50, Hartman CA5, Hoekstra PJ5, Oosterlaan J51, Polier GV11, Konrad K11, Vilarroya O52, Ramos-Quiroga JA53, Soliva JC54, Durston S7, Buitelaar JK55, Faraone SV56, Shaw P57, Thompson PM3, Franke B58.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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