White matter abnormalities may indicate genetic risk for bipolar disorder

White matter (WM) abnormalities in the right temporal lobe may be a marker of genetic risk for bipolar disorder (BD), results from a US study suggest.

The researchers found that BD patients had significantly poorer WM integrity in the right temporal lobe than their unaffected siblings, who, in turn, had significantly poorer WM integrity in this brain region than mentally healthy individuals without a family history of the mood disorder.

"It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD," comment Katie Mahon (Mount Sinai School of Medicine, New York) and team.

Using diffusion tensor imaging (DTI), the researchers assessed WM integrity in 26 patients with BD I or II, 15 of their unaffected siblings, and 27 mentally healthy controls. There were no significant differences between the groups regarding age, gender distribution, or years of education.

Tract Based Spatial Statistics analysis revealed three clusters in close proximity within the right temporal lobe in which fractional anisotropy (FA) values were significantly different between the three groups.

Post hoc analyses indicated that, overall, patients had significantly lower FA values in these clusters than controls, and unaffected siblings had FA values that were intermediate to and significantly different from controls and patients. This same pattern was evident when each of the three clusters was examined individually.

Furthermore, the overall pattern of findings remained similar after excluding BD patients taking antipsychotic medications (n=19), siblings with a DSM-IV-text revision diagnosis (n=3), and patients with a diagnosis of BD II (n=6).

The researchers also found that mean FA values across the three clusters significantly and negatively correlated with the attention subscale of the Barratt Impulsivity Scale version 11 (BIS-11) in unaffected siblings. There were no significant correlations with other BIS-11 subscales.

Mahon and team conclude in Biological Psychiatry: "Our data provide evidence that WM integrity, as inferred by DTI, might serve as an intermediate endophenotype in genetic studies of BD."

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