Fig. 1.

Diagram of the structural equation model (SEM) for white matter connectivity. A separate model was applied to each white matter tract (FA and MD) and each graph theory measure. Water diffusion and graph theory metrics were measured at baseline (age 73) and follow-up (age 76). From each individual bilateral white matter tract, a latent score was calculated for FA and MD. For callosal tracts and graph theory metrics a latent score was derived after the manifest variable was corrected for scaled age at scanning and sex. From these models, a latent change score variable was calculated for each model (Δ Connectivity). Relation between baseline FA/MD/graph theory measures and polygenic risk score for schizophrenia (szPGRS) is indicated by path A; path B represents the association between change in white matter FA/MD/graph theory measures and szPGRS. For all bilateral tracts, we further constrained equality of the factor loading of the left hemisphere (c). szPGRS was corrected for sex and population stratification while water diffusion MRI and graph theory measures at the manifest level were corrected for scaled age at scanning and sex at each time point within the model (paths not shown). Note that graph theory metrics were corrected for density outside the SEM model.