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 cardio-vascular 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, eta 2p = 0.07). In the overall sample, higher venular caliber was significantly associated with lower corpus callosum FA (beta =-0.24, puncorrected = 0.04). In voxel-wise analyses, higher arteriolar caliber was significantly associated with lower corpus callosum and forceps minor FA in the overall sample (beta =-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 (beta = 0.72, p = 0.03), corticospinal tract (beta = 0.72, p = 0.04), and anterior corona radiata (beta = 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.