White matter microstructural integrity is associated with retinal vascular caliber in adolescents with bipolar disorder.

Objective: Reduced white matter integrity is observed in bipolar disorder (BD), and is associated with cardiovascular risk in adults. This topic is underexplored in youth, and in BD, where novel microvascular measures may help to inform understanding of the vascular-brain connection. We therefore examined the association of retinal vascular caliber with white matter integrity in a cross-sectional sample of adolescents with and without BD.

Methods: Eighty-four adolescents (n = 42 BD, n = 42 controls) completed retinal imaging, yielding arteriolar and venular caliber. Diffusion tensor imaging measured white matter fractional anisotropy (FA). Multiple linear regression tested associations between retinal vascular caliber and FA in regions-of-interest; corpus callosum, anterior thalamic radiation, uncinate fasciculus, and superior longitudinal fasciculus. Complementary voxel-wise analyses were performed.

Results: Arteriolar caliber was elevated in adolescents with BD relative to controls (F(1,79) = 6.15, p = 0.02, η = 0.07). In the overall sample, higher venular caliber was significantly associated with lower corpus callosum FA (β = -0.24, p = 0.04). In voxel-wise analyses, higher arteriolar caliber was significantly associated with lower corpus callosum and forceps minor FA in the overall sample (β = -0.46, p = 0.03). A significant diagnosis-by-venular caliber interaction on FA was noted in 5 clusters including the right retrolenticular internal capsule (β = 0.72, p = 0.03), corticospinal tract (β = 0.72, p = 0.04), and anterior corona radiata (β = 0.63, p = 0.04). In each instance, venular caliber was more positively associated with FA in BD vs. controls.

Conclusion: Retinal microvascular measures are associated with white matter integrity in BD, particularly in the corpus callosum. This study was proof-of-concept, designed to guide future studies focused on the vascular-brain interface in BD.