The study - which was funded by the National Institutes of Health (NIH) - is published in The Lancet Psychiatry. It is the work of the ENIGMA Consortium, an international multidisciplinary group that is investigating genetic and brain-imaging differences in psychiatric disorders.
Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that is marked by age-inappropriate symptoms of inattention (such as difficulty sustaining focus), hyperactivity (extreme restlessness, for example), and impulsivity (including hasty actions and excessively interrupting others).
The disorder affects more than 1 in 20 young people under the age of 18. Two thirds of children diagnosed with ADHD continue to experience persistent and impairing symptoms as adults, note the study authors.
Dr. Martine Hoogman, of the department of human genetics at Radboud University Medical Center in Nijmegen, the Netherlands, is principal investigator of the ADHD section of ENIGMA and lead author of the new paper.
She says that the "unprecedented size" of their study is crucial because it helped to identify the "very small - in the range of a few percent" differences in brain region sizes.
"Similar differences in brain volume are also seen in other psychiatric disorders, especially major depressive disorder," adds Dr. Hoogman.
ADHD brains smaller overall and in certain regions
Previous studies have found links between differences in brain volume and ADHD, but they were limited by small sample sizes, making it difficult to draw any firm conclusions.
Nevertheless, these did point to a number of brain differences in ADHD. For example, some suggested that the basal ganglia - an area of the brain that controls emotion, cognition, and voluntary movement - is involved. They found that two regions in the ganglia, the caudate and putamen, tend to be smaller in people with ADHD.
For the new study, Dr. Hoogman and colleagues measured differences in brain structure from MRI scans of 1,713 participants diagnosed with ADHD, and in 1,529 other people (the controls) who did not have ADHD. The participants' ages ranged from 4 to 63 years.
From the MRI scans, the team could assess overall brain volume as well as the size of seven regions of the brain that previous studies have linked to ADHD. These were the caudate nucleus, putamen, nucleus accumbens, pallidum, thalamus, amygdala, and hippocampus.
The results showed that the brains of participants with ADHD were smaller overall, and that volumes of five of the seven regions were also smaller: the caudate nucleus, putamen, nucleus accumbens, amygdala, and hippocampus.
The researchers also took into account whether the participants were taking, or had ever taken, medication to treat ADHD (such as Ritalin), but this appeared to have no effect on the findings.
'Brain disorder characterized by delayed development'
The researchers speculate that the amygdala is linked to ADHD through the part it plays in controlling emotion, and the nucleus accumbens through the role it plays in reward processing. The link between ADHD and the hippocampus could perhaps arise from that region's involvement in motivation and emotion, they suggest.
The differences in brain size were particularly prominent in the children and less obvious in the adults with ADHD, note the authors, who suggest that their findings show that ADHD is a brain disorder characterized by delayed development in several brain regions.
Despite the large numbers of participants of all ages, the study was not designed to investigate how ADHD might develop over a person's lifetime. The team says that there is now a need for longitudinal studies that follow children with ADHD into adulthood and track brain changes over time.
"The results from our study confirm that people with ADHD have differences in their brain structure and therefore suggest that ADHD is a disorder of the brain. We hope that this will help to reduce stigma that ADHD is 'just a label' for difficult children or caused by poor parenting. This is definitely not the case, and we hope that this work will contribute to a better understanding of the disorder."
Dr. Martine Hoogman
Dr. Jonathan Posner, associate professor of psychiatry at Columbia University in New York, was not involved in the study. In a linked comment article, he points out that the uniquely large size of the study means that it is "well powered to detect small effect sizes," which is important when investigating ADHD because of its varied biological and clinical nature.
He notes that the study makes an important contribution by "providing robust evidence to support the notion of ADHD as a brain disorder with substantial effects on the volumes of subcortical nuclei." He also calls for further studies to track brain differences in the development of ADHD, and suggests that there should also be an investigation of any medication effects.