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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