Using complementary ROI-and voxel-based DTI methods, we found decreased FA values in the participants with BD compared to HC participants in anterior and middle CC subregions encompassing the genu, rostral body and the anterior portion of the midbody. The interhemispheric white matter connections of the CC are critical to interhemispheric communication and to the integration of emotional, cognitive, motor and sensory information. Abnormalities in interhemispheric functioning in BD have been theorized previously (12
). Specifically, CC fibers coursing through the anterior CC regions in which differences were detected provide connectivity between right and left prefrontal cortices as well as anterior cingulate and insula (14
). These CC regions are implicated in emotional dysregulation (1
) and in the hemispheric lateralization of prefrontal abnormalities associated with acute mood states of BD (15
). Significant associations between CC FA and clinical features of BD were not detected; however, our ability to detect effects could have been limited by inadequate statistical power.
In a recent DTI study of 11 BD and 10 HC adults that sampled two focal ROIs in the CC genu and splenium, increased FA was detected only in the genu (4
). The different direction of the findings could relate to differences between subject samples or imaging methods. The methods used herein permitted examination of the full CC length. We found differences that covered a larger genu region and that extended to the anterior midbody, implicating a larger section of the anterior CC in BD. The complementary ROI- and voxel-based DTI methods used yielded consistent results and drew upon the relative strengths of each method (16
). ROI-based DTI permitted testing in specific subregions of the CC and minimized the risk of a type I error, whereas voxel-based DTI permitted further localization within the CC. Neither study detected significant group differences in subregional diffusivity (Supplementary Materials
). Furthermore, we did not detect differences in CC cross-sectional areas (Supplementary Materials
). Taken together, the studies suggest that DTI FA measures may be relatively sensitive to the CC white matter abnormalities of BD.
Bipolar disorder frequently co-occurs with substance related disorders (17
). To attempt to balance generalizability of the findings, and potential effects of substances on white matter, we included only BD participants who were in full remission from substance related disorders for at least 1 year. Medication exposure of the BD participants is another potential confound of this study. Although we did not detect significant effects of these factors, and evidence suggests that effects of chronic alcohol and other substances of abuse on the CC may be at least partially reversible with remission (18
), power may have been limited and these analyses did not take into account previous exposures. Further work is necessary to definitively differentiate white matter integrity alterations related to BD from those resulting from medication or substance exposure.
The majority of our BD participants reported symptom onset in adolescence. Interestingly, the CC reaches its maximal myelination in late adolescence/early adulthood (20
), a time period coinciding with this peak in the onset of BD, suggesting that further study of CC development in adolescence/early adulthood in BD may help to elucidate a neurodevelopmental mechanism contributing to the disorder.