Diffusion imaging markers of bipolar versus general psychopathology risk in youth at-risk

Versace, A., Ladouceur, C. D., Graur, S., Acuff, H. E., Bonar, L. K., Monk, K., McCaffrey, A., Yendiki, A., Leemans, A., Travis, M. J., Diwadkar, V. A., Holland, S. K., Sunshine, J. L., Kowatch, R. A., Horwitz, S. M., Frazier, T. W., Arnold, L. E., Fristad, M. A., Youngstrom, E. A., Findling, R. L., Goldstein, B. I., Goldstein, T., Axelson, D., Birmaher, B., Phillips, M. L.


Neuropsychopharmacology p. 1-9


Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.