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 Lisa Jacobson, one of the researchers involved in the study, which appeared Monday in the Journal of the International Neuropsychological Society. “[Our results] tell us that this is not just a behavioral disorder. It is a neurological disorder.”

The study 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, according to 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. The results of the present study in preschoolers mirror those of earlier research in school-age children and adolescents.

“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 acknowledge that the range of “normal” behavior for children this age is wide and variable, 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, according to Jacobson, few if any of the preschoolers in the ADHD group were diagnosed with the disorder prior to the study. Instead, the researchers relied on parental reports after soliciting subjects from the community, often by placing fliers in public places such as libraries.

Experts not associated with the study 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,” wrote Sami Timimi in an email to The Washington Post. Tami is visiting professor of child psychiatry and mental health improvement at Lincoln University in the United Kingdom.

More than 6 million children aged 2-17 living in the United States have been diagnosed with ADHD, according to the most recent statistics from the Centers for Disease Control and Prevention. Thirty years ago, however, the number was half that, suggesting to some critics that the disorder is over-diagnosed today.

“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 of social welfare at the University of California at Los Angeles, points out that more children are treated for ADHD in the United States than in much of the rest of the world. “Findings from brain scans can’t begin to explain this.”

Jacobson and the other scientists who contributed to the research, say they’d like this to be a longitudinal study and follow the children into adolescence. Is there something about the brains of children that are going to show the most persistent symptoms? Jacobson said, “Because that will be the hallmark for treatment.”