Brain-Activation Patterns Change In Youngsters With Bipolar Disorder

What does bipolar disorder do to the brain activity of children? Melissa DelBello, M.D., an assistant professor of psychiatry and pediatrics at the University of Cincinnati, and her colleagues are trying to find out.

And their very preliminary results—results that may change as data from more subjects are analyzed—suggest that the disorder progressively impairs certain brain areas, yet at the same time activates other brain areas, probably in compensation.

DelBello described her study and the preliminary results at the 14th Annual Scientific Symposium of the National Alliance for Research on Schizophrenia and Depression (NARSAD), held in New York City in October. NARSAD showcased some of its most promising younger scientists, such as DelBello, at this symposium.

DelBello and colleagues recruited 12 youngsters with first-episode bipolar disorder and 12 youngsters with multiple-episode bipolar disorder to serve as subjects. They wanted only multiple-episode patients who were completely noncompliant with their medications, so medications could not compromise their study results.

They found their subjects at their university hospital. They also enrolled 12 healthy youngsters of the same age, gender, socioeconomic status, and handedness to serve as controls.

Then came the task of getting their young subjects into a functional magnetic resonance imaging (fMRI) machine. Actually it wasn’t so difficult, DelBello said, since she and her coworkers explained to the young people that it would be like entering a spaceship. But then came the greater challenge of getting the children to hold still, both while they were engaged in a resting task and in a performance task.

The resting task consisted of looking at numbers flashing on a screen. The performance task consisted of pushing a button when they saw the same number flashed twice on a screen. The scientists took a fMRI scan of the brain of each child while the child was engaged in each task.

The researchers then compared fMRI scan results for each subject—that is, from when the subject was simply viewing numbers to when he or she was pressing a button while viewing numbers—to discern which brain areas were activated during the latter period. They then compared brain activation for each subject with brain activation of other subjects in this group. Finally, they compared brain activation of one group with that of the other two groups.

As of now, DelBello and her team have brain activation results for 12 subjects in the control group, 10 in the first-episode group, and six in the multiple-episode group.

These preliminary results reveal less brain activation in prefrontal brain regions and striatal regions such as the basal ganglia of first-episode patients compared with control subjects. These results thus suggest that the prefrontal brain regions and the striatal regions are affected by bipolar disorder.

The findings likewise reveal even less activation in the prefrontal brain regions and striatal regions of multiple-episode subjects compared with first-episode subjects. These findings thus imply that the prefrontal brain regions and striatal regions are increasingly damaged as bipolar disorder takes its toll on the brain.

Interestingly, however, when the brain activation results of multiple-episode subjects are compared with those of first-episode subjects, there is even more activation in the temporal lobes and parietal lobes in the multiple-episode subjects than in the first-episode subjects. “So maybe the multiple-episode subjects are using these brain areas to compensate for those brain areas that have been compromised by bipolar disorder,” DelBello speculated.

In any event, she stressed, these are very preliminary results that may change as fMRI data from all 36 subjects are analyzed. Also, she pointed out, she and her colleagues are going to follow the brain activity of their first-episode subjects over time to see whether bipolar disorder impacts their brains in the same ways that it has those of the multiple-episode patients.

“This is a beautifully designed clinical study,” Lewis Judd, M.D., chair of psychiatry at the University of California at San Diego, declared at the NARSAD symposium. By using first-episode and multiple-episode patients to find out how bipolar illness alters children’s brains over time, he explained, DelBello and her team are getting much quicker results than if they had simply followed the fates of first-episode patients over time.

Psychiatric News asked DelBello what implications her findings have for psychiatrists. “As we understand the brain changes that occur at onset in children with bipolar disorder and that occur over time,” she said, “then we can start to see whether medications can alter these changes.” ▪