A new study has compressed 25 years’ worth of insights into a single paper, and they show the power of looking at the brain in many individuals – in this case, young people -- over a long period of time.

The study, begun in 1989, is called the Longitudinal Structural Magnetic Resonance Imaging Study. The concept is simple: take MRI (magnetic resonance imaging) brain scans in a large group of young people, some developing normally, others with signs and symptoms of behavioral and psychiatric disorders. Begin with children as young as age 5, and at 2-year intervals, have them travel (at no expense) to the National Institutes of Health for an MRI scan, neuropsychological testing, and genetic analysis.

Cumulative findings were published in January in Neuropsychopharmacology by a team led by Judith L. Rapoport, M.D., Chief of Child Psychiatry Branch at the National Institute of Mental Health since 1984, a 2009 NARSAD Distinguished Investigator, and a member of the Foundation’s Scientific Council. The study’s database now consists of over 6,000 MRI scans of over 2,000 subjects. About half the participants have a psychiatric diagnosis and half have been assessed as “typically developing individuals.”

The brain is a work in progress during our early years. What can MRI scans tell us about how the brain typically develops, and how does this “developmental trajectory” differ in children who are diagnosed with disorders?  Can we see things in the brain that characterize these disorders?  Can we make diagnoses on this basis?

One thing Dr. Rapoport and colleagues are clear about at the 25-year mark: MRI scans, though powerful, still cannot be used as the basis for diagnosis. This is because people vary too much. Two healthy individuals can vary greatly in such seemingly important measures as brain size and also with respect to the size of distinct brain areas, such as the cerebral cortex or the hippocampus. Another source of difficulty is that areas of the brain grow at different rates and mature at different rates, and these rates also differ significantly even in healthy people.

After taking all the variables into account, what can be said? The key insights come from comparison of scans of youths in the study who developed normally vs. those who received a diagnosis of ADHD (attention deficit-hyperactivity disorder) and childhood-onset schizophrenia (COS). These are only two of many disorders among participants, but they were used as examples. ADHD is the most commonly diagnosed childhood disorder (5% to 10% of American children receive the diagnosis); COS is one of the least often diagnosed, 500 times rarer than the adult form of the illness, which affects about 1 in 100 adults.  

Scans of many young people over long periods of time revealed clearly to the team that children with ADHD have smaller frontal lobes, parietal lobes, basal ganglia and cerebellums. Over time, such children also typically show a delay in a normal process in which the cortex grows thinner. Most striking of all, they noted, is the middle prefrontal cortex, where peak thickness occurs as much as 5 years later in youths with ADHD before thinning begins. Children who were given stimulant medications tended to revert toward normal brain-developmental “trajectories,” the team noted.

In COS, differences in affected children vs. normally developing children were quite dramatic, and were similar to changes seen in adults. The ventricles are enlarged in those affected, the volume of grey matter in the cortex, hippocampus and amygdala is diminished, while basal ganglia volumes are larger and become more so during adolescence. There is some evidence of delayed white matter development.

Dr. Rapoport and colleagues conclude that MRI scans are “are beginning to elucidate the timing and nature of deviations from typical development that may suggest therapeutic targets.”  They also note that people with similar genetic risk can develop a wide range of disorders, from autism to bipolar disorder to schizophrenia to intellectual disability and epilepsy. Conversely, they add, people with the same outward symptoms often have “numerous individually rare genetic abnormalities.”