Link Found Between ADHD and Brain Size

Could attention-deficit/hyperactivity disorder be related, at least in part, to brain-volume abnormalities?

Such a question is not as far out as it seems. A new study has found that children with the disorder have smaller brain volumes than those without it—and regardless of whether they take medication to treat the disorder.

The study was conducted by F. Xavier Castellanos, M.D., of the New York University Child Study Center, and colleagues and reported in the October 9 Journal of the American Medical Association.

Castellanos and his coworkers launched their study at the Child Psychiatry Branch of the National Institute of Mental Health in Bethesda, Md., in 1991. They recruited from the local community 152 young people with attention-deficit/hyperactivity disorder (ADHD) ranging in age from 5 to 18 years. They appeared to have equally severe ADHD symptoms, since they met identical diagnostic and symptom-severity criteria. The researchers also recruited from the local community 139 young people without the disorder who matched the subjects in age and gender and who were willing to serve as controls.

Castellanos and his team used magnetic resonance imaging (MRI) to measure the brain volumes of the subjects and controls at the start of the study and periodically during the following decade. The areas of the brain that they assessed included the cerebrum, cerebellum, gray and white matter of the four major lobes of the brain, and caudate nucleus.

Finally, they used the MRI scan results to compare the brain volume of the subjects with that of the controls, both at the start of the study and over the subsequent decade.

At the start of the study, the researchers found that the cerebral volume of the subjects was about 3 percent smaller than that of the controls and that the cerebellar volume of the subjects was about 4 percent smaller than that of the controls, even when age, height, weight, and other possibly confounding factors were taken into consideration. These differences were statistically significant.

The initial scans also revealed that the volumes of other brain regions measured were smaller in the subjects as well—again, a statistically significant difference.

Second, they compared initial MRI scan results for only 49 subjects out of the total 152 subjects with those of the controls. These 49 subjects had never received any medication for their disorder, thus allowing the researchers to determine whether medication might have explained the smaller brain volumes that they had found in their subjects. However, it did not seem to, as smaller brain volumes were found in these subjects as well. For instance, both cerebral volume and cerebellar volume were about 6 percent smaller in these subjects than in the controls, and white matter was about 11 percent smaller—again, statistically significant differences.

“In fact, findings were generally as striking for the unmedicated patients with ADHD as for those who were being treated with medications, and were more pronounced for white matter volumes,” the scientists pointed out in their study report.

Finally, they compared MRI scans of all subjects in subsequent years with those taken of the controls in that same period to see whether the initial smaller brain volumes noted in both medicated and unmedicated subjects remained smaller over time. The answer was yes, with the exception of the volume of the caudate nucleus—it caught up with that of the controls.

Thus, it looks as though youngsters with ADHD may have smaller brain volumes than young people without the disorder, that the smaller volumes are not due to medical treatment for the disorder, and that the smaller volumes mostly stay smaller than normal as youngsters with the disorder age, Castellanos and his team concluded.

Whether the smaller volumes play any causal role in the disorder, however, remains to be determined.

The study was financed by the National Institute of Mental Health, Division of Intramural Research Programs.

An abstract of the study, “Developmental Trajectories of Brain Volume Abnormalities in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder,” is posted on the Web at http://jama.ama-assn.org/issues/v288n14/abs/joc20194.html. ▪