In conducting the largest brain imaging study of its kind, an international team of researchers found that ADHD involves decreased volume in key brain regions, in particular the amygdala, which is responsible for regulating the emotions. Although the study, published Wednesday in the Lancet Psychiatry, included children, adolescents and adults, the scientists said the greatest differences in brain volume appeared in the brains of children.

Of seven subcortical brain regions targeted in the study, five, including the amygdala, were found to be smaller in those with ADHD, compared with those in a control group. The other regions that showed reductions in volume were: the caudate nucleus (which has been linked to goal-directed action), the putamen (involved in learning and responding to stimuli), the nucleus accumbens (which processes rewards and motivation) and the hippocampus (where memories are formed).

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The first author, geneticist Martine Hoogman of Radboud University in the Netherlands, said the amygdala “is a structure that is not so well known to be implicated in ADHD. … We do know from other functional studies of the amygdala that it is involved in emotion regulation and recognizing emotional stimuli. But it is also involved in the process of [inhibiting] a response. Both cognitive processes are characteristic of ADHD, so it does make sense to have found this structure to be implicated in ADHD.”

The research was conducted by an ADHD working group that is part of a worldwide consortium called ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis). The group aims to bring together scientists in fields such as imaging, genomics, neurology and psychiatry to better understand brain structure and function. Its ADHD project was four times the size of the previously largest study and was conducted at 23 locations in nine countries by 80 researchers, primarily psychiatrists and neuroscientists.

A total of 3,242 people, ages 4 to 63, underwent MRI brain scans. Almost half of them had been diagnosed with ADHD. The other half were control subjects.

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“The reliability of ADHD research has not been great, because of [small] sample sizes,” said Jonathan Posner, who did not take part in the study but who does pediatric brain imaging research at Columbia University Medical School. “So because this study was orders of magnitude higher in terms of participants, and because it involved sampling broadly and internationally, it gives us more confidence.”

By being able to point to measurable differences in the brains of those with ADHD, the ENGIMA scientists hope their study will also help the general public better understand the disorder.

“I think most scientists in the field already know that the brains of people with ADHD show differences, but I now hope to have shown convincing evidence … that will reach the general public,” said Hoogman, “and show that it has [a basis in the brain] just like other psychiatric disorders. … We know that ADHD deals with stigma, but we also know that increasing knowledge will reduce stigma.”

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The researchers were able to conclude that the brain differences were not related to medication people took, to other psychiatric disorders people with ADHD may also have had, or even to the severity of their symptoms.

The smaller brain structures in children with ADHD but not in adults fits with a “delayed peak volume” theory that ADHD is associated with an “altered velocity of cortical development,” the authors said. That is, their brain development may be delayed compared with children who do not have ADHD, but it may catch up as they grow into adulthood.

Finding that the amygdala, the brain's emotional regulator, had the greatest volume reduction in ADHD was particularly important to the researchers because of the ubiquity of emotional problems in the disorder. The study might be relevant for updates to the Diagnostic and Statistical Manual, the guidebook psychiatrists use to identify conditions. “Those [emotional] symptoms are often present in patients with ADHD,” the authors wrote, “but these disease characteristics have not [yet] been included into the official DSM criteria.”