Brain volume may be potential risk factor for ADHD

By Larry Hand

NEW YORK (Reuters Health) - Individuals with attention-deficit/hyperactivity disorder (ADHD) appear to have smaller total brain and gray matter volumes than individuals without ADHD, and unaffected siblings in ADHD families appear to have intermediate volumes, new research shows.

"Similar brain volumetric differences that were found in participants with ADHD, relative to control participants, were also found in unaffected siblings, although the differences found in unaffected siblings were somewhat smaller," Dr. Corina U. Greven, of the Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands, told Reuters Health by email.

"Hence, it is possible that these brain volumes may be potential risk markers indicating familial vulnerability for ADHD," she said. A unique aspect of this new study "is the inclusion of unaffected siblings, i.e. brothers and sisters of participants with ADHD who themselves do not have ADHD."

Dr. Greven and her colleagues analyzed data from the Dutch part of the International Multicenter ADHD Genetics Study (IMAGE) conducted between 2003 and 2006. Participants came from families with at least one child with ADHD and one biological sibling without ADHD, or from control families with at least one child and a biological sibling with no ADHD, all between the ages of 8 and 30.

IMAGE researchers conducted magnetic resonance imaging at two locations with comparable scanners and protocols to obtain whole-brain and subcortical volume measures. They also collected data on cumulative medicine intake (treatment duration corrected for age and multiplied by the mean daily dose).

In the new study, Dr. Greven and colleagues analyzed data on 307 individuals with ADHD, 169 unaffected siblings, and 196 controls. Participants had a mean age of about 17. The ADHD group consisted of 68% male participants, but the other two groups were close to even on gender.

They found that individuals with ADHD had total brain volume about 2.5% smaller than controls and total gray matter volume about 3% smaller than controls (p=0.0005). Differences remained stable across sex and age analysis, they report in an article published online March 18 in JAMA Psychiatry.

They found that total brain volume in unaffected siblings was 1.6% larger and total gray area was 1.8% larger than brothers or sisters with ADHD (p=0.03). Differences between unaffected siblings and controls came to nonsignificant 0.9% smaller total brain and 1.3% smaller total gray matter volumes.

They also linked ADHD to smaller caudate (p<0.001) and putamen (p=0.01) volumes with significant age-by-diagnosis interactions.

They saw no association between cumulative medicine use and brain volumes in individuals with ADHD. This finding, they wrote, warrants further research into whether stimulant medication has a normalizing effect on structural brain alterations.

"Findings in the unaffected siblings provided evidence that total brain, gray matter, caudate, and putamen volumes are linked to familial risk for ADHD. As familial underpinnings of ADHD are thought to be largely genetic, it is plausible that genetic mechanisms may underlie the reported ADHD-brain associations, creating possible new targets for molecular genetic research," the researchers wrote.

"The present study used a particularly large sample of participants with ADHD and control participants who all had MRI scans. The uniqueness of the sample is that it includes the turning point from adolescence into young adulthood, a developmental period frequently neglected in previous research," Dr. Greven told Reuters Health.

However, she cautions against overinterpretation: "Our findings provide scientifically novel ideas about what is happening in the brain in individuals with ADHD and allow a sharper focus on brain regions that might be relevant for ADHD. It is important to note that our findings are based on group averages and are not suitable to draw inferences about individuals. Hence, based on this study, an MRI scan to determine a person's brain volume is not suitable as a diagnostic test for the individual."

The U.S. National Institutes of Health, the Netherlands Organization for Scientific Research, and Radboud University supported this research.

SOURCE: http://bit.ly/1xmbjXv

JAMA Psychiatry 2015.

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