Sex-Based Brain Differences Visible in Kids With ADHD

Nancy A. Melville

January 08, 2015

Boys and girls with attention-deficit/hyperactivity disorder (ADHD) show differences in brain structure that are consistent with observed differences in clinical presentation between the sexes, a new imaging study shows.

Using magnetic resonance imaging (MRI) to compare brain structure in boys and girls with ADHD with that of normally developing children, researchers found that boys with ADHD show reductions in premotor cortex surface area of the brain compared with children without ADHD, whereas girls in the same age group show reductions in the prefrontal cortex surface area, more associated with organizational skills.

"Our findings suggest that boys, at least in this age range, demonstrate more problems with motor control, whereas the girls show more abnormalities in circuits responsible for a higher level of organization and planning," coauthor Stewart Mostofsky, MD, director of the Center for Neurodevelopmental and Imaging Research at Kennedy Krieger Institute in Baltimore, Maryland, told Medscape Medical News.

The study was published in the January issue of NeuroImage: Clinical.

Examining Brain Structure

Although ADHD research looking at sex differences has focused largely on functional comparisons, research evaluating brain structure of boys and girls with ADHD has been lacking, with only one other study looking at differences in frontal lobe morphology.

For this study, Dr Mostofsky and colleagues used 3T magnetization–prepared rapid gradient-echo (MP-RAGE) MRI to scan the brains of 226 children between the ages of 8 and 12 years. Among the children, 93 had ADHD, including 29 girls, and 133 were experiencing normal development, including 42 girls.

Using a newly developed automated frontal lobe atlas, the researchers found overall reductions in total prefrontal cortex surface area in girls with ADHD, but not in boys, compared with the same-sex normal control individuals.

Boys with ADHD, but not girls, showed overall reductions in total premotor cortex surface area compared with the same-sex normal control individuals.

Whereas boys' premotor reductions were seen in bilateral premotor cortex regions, the prefrontal reductions in girls were in bilateral supplementary motor complex. There were no significant differences in cortical thickness between the groups.

The authors speculated that the differences could simply represent different stages of development that are typically seen between girls and boys of the same age.

"We know it's well established that girls mature earlier than boys, and that pattern also includes early maturation of brain structure and associated functions," said Dr Mostofsky.

"It's also known that motor function matures earlier than prefrontal structure, so given that, it could be possible that if we had looked, for instance, at the girls earlier, we may have seen similar motor problems that the boys showed later," he added.

"We hope to better understand with follow-up longitudinal studies whether or not the differences we're seeing in this prepubertal window of time are due to differences in developmental lag."

If the differences are found to persist despite developmental stage, however, these distinctions would line up with the bulk of evidence, albeit limited, on functional differences between boys and girls with ADHD, the authors note.

"Clinically, boys are more commonly diagnosed with the combined subtype and show a greater preponderance of hyperactive/impulsive symptoms, whereas girls with ADHD are more often diagnosed with the inattentive subtype," they write.

In the study, approximately 70% of patients with ADHD were prescribed stimulant medication at the time of the study, and although no significant effect of the medication was seen regarding premotor cortex surface area, differences in the prefrontal cortex among ADHD patients and normal control individuals were more exaggerated among patients on the medications.

Dr Mostofsky noted that patients on medications had greater severity of symptoms at baseline, which may have explained the differences.

Important Step Forward

Commenting on the findings for Medscape Medical News, Cathryn A. Galanter, MD, director of the Child and Adolescent Psychiatry Training Program at SUNY Downstate/Kings County Hospital Center in New York City, agreed that additional studies should help clarify potential clinical implications of the findings.

"Further research with larger samples and further neuropsychiatric correlates are needed before we can make conclusions on the treatment of children with ADHD," she said.

Nevertheless, she added, the study represents an important step forward in that understanding.

"This study is very promising and highlights the importance of better understanding how boys and girls with ADHD may present differently. Ultimately, as careful clinicians, we should use data such as these to inform our decision making."

"Children with ADHD or suspected ADHD still need a careful and comprehensive clinical assessment and a treatment plan that addresses different domains, including functioning in school, with family, and with peers."

The authors have disclosed no relevant financial relationships. Dr Galanter is on the Scientific Steering Committee of the Primary Pediatric Psychopharmacology Fellowship of the REACH Institute and receives royalties from American Psychiatric Publishing, Inc.

Neuroimage Clin. 2015;7:222–229. Full text

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