White matter microstructural impairments and genetic liability to familial bipolar I disorder.

BACKGROUND Subtle abnormalities in frontal white matter have been reported in bipolar disorder. AIMS To assess whether impaired integrity of white matter tracts is associated with bipolar disorder and genetic liability for the disorder. METHOD A total of 19 patients with psychotic bipolar I disorder from multiply affected families, 21 unaffected first-degree relatives and 18 comparison individuals (controls) underwent diffusion tensor imaging. Whole brain voxel-based analyses compared fractional anisotropy between patients and relatives with controls, and its relationship with a quantitative measure of genetic liability. RESULTS Patients had decreased fractional anisotropy compared with controls in the genu of the corpus callosum, right inferior longitudinal fasciculus and left superior longitudinal fasciculus. Increased genetic liability for bipolar disorder was associated with reduced fractional anisotropy across distributed regions of white matter in patients and their unaffected relatives. CONCLUSIONS Disturbed structural integrity within key intra- and interhemispheric tracts characterises both bipolar disorder and genetic liability for this illness.