Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder

Background: Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. Methods: We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD (n = 26), unaffected siblings of patients with BD (n = 15), and healthy volunteers (n = 27) to identify WM biomarkers of genetic risk. Results: The FA differed significantly (p < .05; corrected) among the three groups within the right temporal WM. Unaffected siblings had FA values that were intermediate to and significantly different from those of healthy volunteers and patients with BD (healthy control subjects > unaffected siblings > BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Conclusions: Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. 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.