In the first comprehensive imaging study of attention-deficit/hyperactivity disorder in preschoolers, researchers have found evidence that structural changes in the brain are already recognizable at the age of 4.

“One of our big questions was thinking about an early-onset disorder and linking it to early onset brain anomalies,” said researcher Lisa Jacobson. “[Our results] tell us that this is not just a behavioral disorder. It is a neurological disorder.”

The study in the Journal of the International Neuropsychological Society found widespread reductions in the volume of gray matter in the brains of children with ADHD. And the more severe their behavior, the more their brains differed from those of children who had not been diagnosed with ADHD, said Jacobson, a pediatric neuropsychologist at Johns Hopkins and the Kennedy Krieger Institute, an affiliate of Johns Hopkins and the site of the research. The most significant differences in brain volume were seen in the temporal and prefrontal lobes, including areas associated with activity, attention, and motor control.

“When they designed the study, even Mark Mahone[the lead author] did not think he would find these differences,” said James Griffin of the National Institutes of Health, which funded the research. Griffin is the deputy chief of NIH’s Child Development and Behavior branch. “They were surprised at how early these differences were already evident in the brain.”

The authors acknowledged that the range of “normal” behavior for children this age is wide, and that these brain differences are merely associated with, and not necessarily the cause of, the symptoms of ADHD. They also note that children’s brains don’t all develop along the same timeline.

Another issue is that, Jacobson said, few if any of the preschoolers in the ADHD group had the diagnosis before the study. Instead, the researchers relied on parental reports.

Outside experts also cited the difficulty of making conclusions based on averages of the two groups. “Focusing on this gives a false impression of the two samples and tells us nothing about the spread found in the two groups,” said Sami Timimi, a visiting professor at Lincoln University in the United Kingdom.

More than 6 million U.S. children ages 2 to 17 have ADHD diagnoses, said the Centers for Disease Control and Prevention. Thirty years ago, the number was half that, suggesting to some critics that the disorder is over-diagnosed.

“Brain size, like every biological trait, lies on a spectrum,” said Jonathan Leo, professor of neuroanatomy at Lincoln University in Tennessee.

David Cohen, a professor at the University of California at Los Angeles, points out that more children are treated for ADHD in the U.S. than in much of the rest of the world. “Findings from brain scans can’t begin to explain this.”