Confirmed: ADHD Brain Is Different

Megan Brooks

February 23, 2017

The structure of the brain of children with attention-deficit/hyperactivity disorder (ADHD) differs from that of normally developing children ― a difference that is clearly visible on MRI. This suggests that ADHD should be considered a neurologic disorder, researchers say.

In the largest imaging study of ADHD conducted to date, investigators found that five regions of the brain were slightly smaller in children with ADHD compared to children without the disorder.

"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," principal investigator Martine Hoogman, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in statement.

The study was published online February 15 in the Lancet Psychiatry.

Novel Collaboration

Until now, neuroimaging studies of patients with ADHD have been small and heterogeneous in their methods, leading to "inconclusive results about structural brain differences in ADHD," Dr Hoogman told Medscape Medical News.

To overcome these limitations and to conduct collaborative studies of "maximal power," the researchers founded the ENIGMA ADHD Working Group in 2013 to aggregate structural MRI data from participants with ADHD and healthy control persons across the lifespan, the researchers note.

"We tried to reuse all the efforts that have been put in the individual imaging studies and reanalyze all the raw data again using homogenized methods. This has resulted in a large sample size with adequate power to detect small changes in the brains of people with ADHD," said Dr Hoogman.

The researchers assessed differences in the subcortical structures and intracranial volume on MRI scans of 1713 individuals with ADHD and 1529 unaffected control persons across 23 sites. The participants ranged in age from 4 years to 63 years (median age, 14 years).

In this "mega-analysis," patients with ADHD were found to have reductions in the volumes of the accumbens, the amygdala, the caudate, the hippocampus, and the putamen (Cohen's d = -0.15, -0.19, -0.11, -0.11, and -0.14, respectively), as well as reductions in intracranial volume (Cohen's d = -0.10).

The differences in the brains of people with ADHD uncovered in the study have "similar effect sizes as those of depression or obsessive compulsive disorder," said Dr Hoogman said.

The differences were most prominent in the brains of children with ADHD. They were less obvious in adults with the disorder, which supports the notion that ADHD is a disorder of the brain and that delays in the development of these brain regions are characteristic of ADHD, she noted.

At the time of brain MRI scanning, 455 people with ADHD were taking psychostimulant medication; 637 had taken psychostimulant medication at some time in their lifetime. The observed differences in the five brain regions involved in ADHD were independent of psychostimulant medication, suggesting that the differences in brain volumes were not a result of the medication, the researchers note.

Dr Hoogman said that "at this point in time," there is no role for MRI in the diagnosis of ADHD.

"Unfortunately, we are not there yet. The results of this study might help to get a better understanding of the neurobiology of ADHD, but using an MRI scan to diagnose ADHD is not possible," she said. The differences between people with and those without ADHD are "really small, and there is a lot of individual variability in the volumes," she noted.

Dr Hoogman believes it would be worthwhile to do more research similar to this study, "with large sample sizes and enough statistical power," but focusing on other parts of the brain (the cortex, or connections between brain areas). "Hopefully, this will contribute to a complete picture of the neural substrates of ADHD."

Important Contribution

The coauthors of a linked commentary say the ENIGMA collaboration "laudably embodies the collaborative spirit of data sharing and the type of science that the field should strive to make commonplace."

Jonathan Posner, MD, and Claudia Lugo-Candelas, PhD, of Columbia University in New York City, note that the study "replicates previously documented volume reductions in the caudate and putamen in individuals with ADHD, yet also makes a novel contribution by being the first meta-analysis, to their knowledge, to document accumbens, hippocampal, and amygdala differences in their mega-analysis."

"This study represents an important contribution to the field by providing robust evidence to support the notion of ADHD as a brain disorder with substantial effects on the volumes of subcortical nuclei. Future meta-analyses and mega-analyses will need to investigate medication effects as well as the developmental course of volumetric differences in this disorder," the authors of the commentary conclude.

The study was funded by the National Institutes of Health. A complete list of author disclosures is available with the original article.

Lancet Psychiatry. Published online February 15, 2017. Abstract, Commentary

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