Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia: a multisite harmonization study.
Seitz-Holland J., Wojcik JD., Cetin-Karayumak S., Lyall AE., Pasternak O., Rathi Y., Vangel M., Pearlson G., Tamminga C., Sweeney JA., Clementz BA., Schretlen DA., Viher PV., Stegmayer K., Walther S., Lee J., Crow T., James A., Voineskos A., Buchanan RW., Szeszko PR., Malhotra AK., Kelly S., Shenton ME., Keshavan MS., Mesholam-Gately RI., Kubicki M.
Cognitive deficits are among the best predictors of real-world functioning in schizophrenia. However, our understanding of how cognitive deficits relate to neuropathology and clinical presentation over the disease lifespan is limited. Here, we combine multi-site, harmonized cognitive, imaging, demographic, and clinical data from over 900 individuals to characterize a) cognitive deficits across the schizophrenia lifespan and b) the association between cognitive deficits, clinical presentation, and white matter (WM) microstructure. Multimodal harmonization was accomplished using T-scores for cognitive data, previously reported standardization methods for demographic and clinical data, and an established harmonization method for imaging data. We applied t-tests and correlation analysis to describe cognitive deficits in individuals with schizophrenia. We then calculated whole-brain WM fractional anisotropy (FA) and utilized regression-mediation analyses to model the association between diagnosis, FA, and cognitive deficits. We observed pronounced cognitive deficits in individuals with schizophrenia (p