School of Medicine Publications and Presentations
Document Type
Article
Publication Date
11-1-2013
Abstract
Objective
Several lines of evidence indicate that white matter integrity is compromised in bipolar disorder, but the nature, extent, and biological causes remain elusive. To determine the extent to which white matter deficits in bipolar disorder are familial, the authors investigated white matter integrity in a large sample of bipolar patients, unaffected siblings, and healthy comparison subjects.
Method
The authors collected diffusion imaging data for 64 adult bipolar patients, 60 unaffected siblings (including 54 discordant sibling pairs), and 46 demographically matched comparison subjects. Fractional anisotropy was compared between the groups using voxel-wise tract-based spatial statistics and by extracting mean fractional anisotropy from 10 regions of interest. Additionally, intra-class correlation coefficients were calculated between the sibling pairs as an index of familiality.
Results
Widespread fractional anisotropy reductions in bipolar patients (>40,000 voxels) and more subtle reductions in their siblings, mainly restricted to the corpus callosum, posterior thalamic radiations, and left superior longitudinal fasciculus (>2,000 voxels) were observed. Similarly, region-of-interest analysis revealed significant reductions in most white matter regions in patients. In siblings, fractional anisotropy in the posterior thalamic radiation and the forceps was nominally reduced. Significant between-sibling correlations were found for mean fractional anisotropy across the tract-based spatial statistic skeleton, within significant clusters, and within nearly all regions of interest.
Conclusions
These findings emphasize the relevance of white matter to neuropathology and familiality of bipolar disorder and encourage further use of white matter integrity markers as endophenotypes in genetic studies.
Recommended Citation
Sprooten, E., Brumbaugh, M. S., Knowles, E. E., McKay, D. R., Lewis, J., Barrett, J., Landau, S., Cyr, L., Kochunov, P., Winkler, A. M., Pearlson, G. D., & Glahn, D. C. (2013). Reduced white matter integrity in sibling pairs discordant for bipolar disorder. The American journal of psychiatry, 170(11), 1317–1325. https://doi.org/10.1176/appi.ajp.2013.12111462
First Page
1317
Last Page
25
Publication Title
The American journal of psychiatry
DOI
10.1176/appi.ajp.2013.12111462
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
PMC Copyright notice