Seitz-Holland, Johanna; Wojcik, Joanne D; Cetin-Karayumak, Suheyla; Lyall, Amanda E; Pasternak, Ofer; Rathi, Yogesh; Vangel, Mark; Pearlson, Godfrey; Tamminga, Carol; Sweeney, John A; Clementz, Brett A; Schretlen, David A; Viher, Petra Verena; Stegmayer, Katharina; Walther, Sebastian; Lee, Jungsun; Crow, Tim; James, Anthony; Voineskos, Aristotle; Buchanan, Robert W; ... (2022). Cognitive deficits, clinical variables, and white matter microstructure in schizophrenia: a multisite harmonization study. Molecular psychiatry, 27(9), pp. 3719-3730. Springer Nature 10.1038/s41380-022-01731-3
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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).
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center 07 Faculty of Human Sciences > Institute of Psychology |
UniBE Contributor: |
Viher, Petra, Stegmayer, Katharina Deborah Lena, Walther, Sebastian |
Subjects: |
600 Technology > 610 Medicine & health 100 Philosophy > 150 Psychology |
ISSN: |
1476-5578 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Sebastian Walther |
Date Deposited: |
22 Aug 2022 16:43 |
Last Modified: |
05 Dec 2022 16:22 |
Publisher DOI: |
10.1038/s41380-022-01731-3 |
PubMed ID: |
35982257 |
BORIS DOI: |
10.48350/172208 |
URI: |
https://boris.unibe.ch/id/eprint/172208 |
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