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Both bipolar disorder and genetic liability for the condition are characterized by disturbances to the structural integrity within specific intra- and interhemispheric tracts within the brain, conclude scientists.
Previous studies have revealed white matter hyperintensities and volume deficits on structural magnetic resonance imaging in bipolar disorder patients and unaffected relatives at high genetic liability, as well as white matter coherence impairments in frontal regions on diffusion tensor imaging (DTI).
To examine changes in fractional anisotropy in the whole brain, Christopher Chaddock, from the Institute of Psychiatry in London, UK, and colleagues performed DTI on 19 psychotic bipolar I disorder patients, 21 unaffected first-degree relatives, and 18 healthy controls.
Brain voxel-based analysis was used to compare fractional anisotropy for patients, relatives, and controls, and related to findings on a genetic liability scale in unaffected relatives.
The three groups were similar in terms of age, gender, handedness, full-scale IQ, years of education, and parental social class. All patients were in illness remission, despite experiencing subsyndromal symptoms. The average duration of illness was 15.6 years.
Compared with controls, patients had significant fractional anisotropy reductions in a bilateral frontal cluster extending from deep frontal white matter to include the genu of the corpus callosum and a left lateralized portion of the internal capsule, a right temporal cluster extending superiorly toward the parietal lobe, and a superior frontal cluster.
In addition, fractional anisotropy was strongly correlated among brain regions, with the first principal component accounting for 88% of the total variance. The cluster associations were unaffected by gender, current versus no medication, symptom scores, or number of hospitalizations.
In contrast, no significant clusters of either increased or decreased fractional anisotropy were detected between unaffected relatives and controls, the team writes in the British Journal of Psychiatry.
They did find, however, that increasing genetic liability for bipolar disorder was significantly associated with lower fractional anisotropy in 70 distributed clusters incorporating several white matter tracts, including the cerebellum and brainstem, longitudinal fasciculus and unicate, and bilateral deep frontal white matter. This negative correlation was identified in both patients and unaffected relatives, at r values of -0.814 and -0.717, respectively.
The team concludes: “It is not possible to clarify the exact cause of a reduction in fractional anisotropy, as this can be influenced by a change in the organization or orientation of white matter tracts, a reduction in density of white matter fibres or a reduction in myelination.
“In bipolar disorder, there is some evidence pointing to a role of disrupted myelination, with increased apoptosis and necrosis of oligodendrocytes and a downregulation of myelination and oligodendrocyte-related genes previously identified.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
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Older bipolar disorder patients have inferior frontal lobe gray matter volume deficits, including in areas associated with the anterior limbic network, US researchers have discovered.
Although structural magnetic resonance imaging (MRI) studies have revealed inconsistent results in the assessment of volumetric changes in bipolar disorder patients, several investigations have indicated that regional abnormalities are present in such patients, predominantly in the frontal and temporal lobes.
John Beyer and colleagues from Duke University Medical Center in Durham, North Carolina administered structured clinical interviews and performed MRI scanning on 56 bipolar disorder patients with an average age of 60.5 years and 43 healthy individuals with an average age of 58.1 years. The cerebrum was divided into 16 units using image parcellation.
There were no significant differences between patients and controls in terms of age, gender, or race, the team notes in the International Journal of Geriatric Psychiatry. There were also no differences in total gray matter volume between patients and controls.
However, analysis revealed a significant bilateral difference in gray matter volume in patients versus controls in the anterior half of the brain, particularly in the anterior??”inferior brain regions. This difference remained significant even after controlling for age and gender.
Again, no overall total white matter volume differences were observed between patients and controls. Some differences were found in anterior brain regions, but these did not remain after taking into account age and gender.
“Our observation of decreased gray matter volume in the inferior frontal areas of the brain suggests that these areas may play a primary role in the mood and cognitive symptoms of bipolar disorder, and complements previous structural neuroimaging studies that suggest an underlying neuropathology in the anterior limbic network,” the researchers conclude.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009