TY - JOUR
T1 - Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia
T2 - a multisite harmonization study
AU - Seitz-Holland, Johanna
AU - Wojcik, Joanne D.
AU - Cetin-Karayumak, Suheyla
AU - Lyall, Amanda E.
AU - Pasternak, Ofer
AU - Rathi, Yogesh
AU - Vangel, Mark
AU - Pearlson, Godfrey
AU - Tamminga, Carol
AU - Sweeney, John A.
AU - Clementz, Brett A.
AU - Schretlen, David A.
AU - Viher, Petra Verena
AU - Stegmayer, Katharina
AU - Walther, Sebastian
AU - Lee, Jungsun
AU - Crow, Tim
AU - James, Anthony
AU - Voineskos, Aristotle
AU - Buchanan, Robert W.
AU - Szeszko, Philip R.
AU - Malhotra, Anil K.
AU - Kelly, Sinead
AU - Shenton, Martha E.
AU - Keshavan, Matcheri S.
AU - Mesholam-Gately, Raquelle I.
AU - Kubicki, Marek
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/9
Y1 - 2022/9
N2 - 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 < 0.006), associated with more positive symptoms and medication dosage. Regression-mediation analyses showed that WM microstructure mediated the association between schizophrenia and language/processing speed/working memory/non-verbal memory. In addition, processing speed mediated the influence of diagnosis and WM microstructure on the other cognitive domains. Our study highlights the critical role of cognitive deficits in schizophrenia. We further show that WM is crucial when trying to understand the role of cognitive deficits, given that it explains the association between schizophrenia and cognitive deficits (directly and via processing speed).
AB - 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 < 0.006), associated with more positive symptoms and medication dosage. Regression-mediation analyses showed that WM microstructure mediated the association between schizophrenia and language/processing speed/working memory/non-verbal memory. In addition, processing speed mediated the influence of diagnosis and WM microstructure on the other cognitive domains. Our study highlights the critical role of cognitive deficits in schizophrenia. We further show that WM is crucial when trying to understand the role of cognitive deficits, given that it explains the association between schizophrenia and cognitive deficits (directly and via processing speed).
UR - http://www.scopus.com/inward/record.url?scp=85136318963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85136318963&partnerID=8YFLogxK
U2 - 10.1038/s41380-022-01731-3
DO - 10.1038/s41380-022-01731-3
M3 - Article
C2 - 35982257
AN - SCOPUS:85136318963
SN - 1359-4184
VL - 27
SP - 3719
EP - 3730
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 9
ER -