White matter integrity supports heritability of bipolar disorder

By Eleanor McDermid, Senior medwireNews Reporter

Researchers have detected widespread white matter integrity reductions in patients with bipolar disorder, which extend to their unaffected siblings.

“Together, these results suggest an important role for white matter integrity in the pathology of bipolar disorder and support the validity of white matter integrity as an endophenotype for the illness,” the team writes in TheAmerican Journal of Psychiatry.

Using diffusion tensor imaging, the researchers found significant reductions in integrity across the whole white-matter skeleton in 64 bipolar disorder patients relative to 46 control participants, after adjusting for age and gender. These changes correlated with duration of illness, and also with Lifetime Dimensions of Psychotic Symptoms scores, suggesting that they related directly to the pathology of the illness.

The team also looked at specific regions of interest in three categories (limbic and frontotemporal connections, thalamic tracts, and callosal regions) and found that patients had reduced white matter integrity in most regions.

Imaging of 60 full siblings of the patients (54 sibling pairs) revealed significant reductions in white matter integrity versus controls, but these reductions were smaller than those in the patients, and restricted mainly to the splenium of the corpus callosum, the posterior thalamic radiations, and the left superior longitudinal fasciculus.

“These results could reflect a true localization of familial influence in these regions, implying that fractional anisotropy reductions in other areas are determined by illness-specific factors,” say lead study author Emma Sprooten (Yale University School of Medicine, New Haven, Connecticut, USA) and colleagues.

But they add that it may simply be easier to detect subtle differences in the “large, well-defined fiber bundles” present in these regions.

“Thus, while our results suggest that the familial aspect of fractional anisotropy reductions is restricted to a set of specific tracts, we cannot rule out a more global effect masked by differential sensitivity across the white matter skeleton.”

However, white matter integrity highly correlated between siblings, which, together with the mild reductions in unaffected siblings, leads the researchers to “postulate that a shared set of genes are responsible for white matter abnormalities and risk for bipolar disorder.”

They add that their results support the idea that changes in white matter integrity is one pathway by which risk genes can lead to bipolar symptoms. “If so, investigating white matter integrity in molecular and cellular studies may provide new insights into downstream biological pathways and mechanisms of risk genes and may ultimately result in the identification of new medication targets.”

Free abstract http://ajp.psychiatryonline.org/article.aspx?articleid=1764123

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