Bipolar Brains Exhibit Structural Abnormalities


STOCKHOLM – The brains of bipolar patients show specific regional abnormalities that may be associated with the neurocognitive deficits that bipolar patients exhibit, Jair Soares, M.D., said at the annual meeting of the European College of Neuropsychopharmacology.

It is worth noting, however, that some of these anatomic abnormalities are seen even in the brains of pediatric bipolar patients, so it's unclear whether the changes are neurodevelopmental or neurodegenerative, said Dr. Soares of the University of Texas, San Antonio.

He has collaborated on several brain imaging studies that have consistently identified structural changes in the bipolar brain. Although these studies are small and must be interpreted cautiously, he said, taken together, they paint a picture of a brain that may be fundamentally different from childhood on.

His recently published study of 27 adult bipolar patients (11 untreated and 16 on lithium monotherapy) and 39 healthy controls showed the relationship between the illness, lithium treatment, and cingulate volume. The 11 untreated patients had significantly decreased left anterior cingulate volumes, compared with both the healthy controls and the treated bipolar patients. The cingulate volumes of the treated patients were not different from those of controls (Biol. Psych. 2004;56:467-75).

The cingulate is not the only abnormal area that has been documented in the brains of bipolar patients, Dr. Soares said. The volume of the amygdala and conductivity of the corpus callosum are also abnormal.

In another study of brain anatomy in bipolar subjects, he and his associates examined 24 bipolar patients and 36 healthy controls. Bipolar patients had significantly larger left amygdala volumes compared with controls (J. Psychiatr. Res. 2003;37:287-95).

A 2004 study in which Dr. Soares was involved found lower MRI signal intensity in the corpus callosa of 29 bipolar patients, compared with those of 23 unipolar patients and 36 healthy controls (J. Neurol. Neurosurg. Psych. 2004;75:221-5). “This suggests that there are abnormalities that might reflect abnormal myelination,” he said.

“And this could be responsible for some of the neurocognitive abnormalities that bipolar patients display.”

Bipolar patients also show increased areas of hyperintense abnormalities on MRI scans. “These are very nonspecific abnormalities that are often related to vascular changes. They are very prevalent in late-life depression and in patients with bipolar disorder. These might represent disruptions of specific brain pathways that interconnect areas involved in mood regulation,” he suggested.

Bipolar brains seem to lose gray matter at an accelerated rate.

“We all lose gray matter as we age, but bipolar patients seem to start losing this much earlier,” Dr. Soares said. A 2004 study of 22 bipolar patients and 22 healthy controls, all of middle age, found that age was not associated with gray matter volume in the controls.

In the bipolar patients, however, gray matter volume was inversely related to age (Neuropsychobiology 2001;43:242-7).

“They were losing it at a faster rate as they got older. Because the groups were similar in age this suggests there is a neurodegenerative mechanism in bipolar patients,” he said.

Changes are evident even in the brains of adolescents with bipolar disorder. In a recent study on which he collaborated, investigators measured temporal lobe structures in 16 adolescents with bipolar disorder and 21 healthy controls and found decreased cingulate volumes in the left anterior, left posterior, and right posterior quadrants.

“This is interesting because in the adult study, we only found a change in the left anterior,” Dr. Soares said. “The pediatric study found more extensive cingulate changes.” These results might have been confounded by selection bias, he noted. The bipolar patients in the pediatric study represented early-onset disease, and so might have had a more severe form of the disorder.

Although the brains of adult bipolar patients display an increased amygdala volume, adolescent bipolar brains display a smaller volume, according to a study of both bipolar adolescents and healthy controls (Biol. Psychiatry 2004;56:399-405).

In this study, the left amygdalas of the subjects with bipolar disorder were smaller than those of the controls, a finding that has been replicated in two additional recent studies.

“Why is the amygdala smaller in bipolar children and larger in bipolar adults?” Dr. Soares asked. “What is it in the developmental years that causes this to happen?”

One explanation is that the bipolar brain may fail to control amygdala growth. “In controls, there is an inverse relation in size as the child increases in age.

This might reflect some kind of pruning mechanism in those years” that does not occur in people with bipolar disorder, he said.

There is mounting evidence that lithium treatment may prevent or even reverse some of these changes. The study that showed normal cingulate volumes in bipolar adults on lithium monotherapy and decreased volume in untreated bipolar adults showed lithium's association with an improved anatomic profile.

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