Associations between cognition and white matter microstructure in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls: A multivariate pattern analysis

Abstract

Background: Cognitive functions have been associated with white matter (WM) microstructure in schizophrenia, but most studies are limited by examining only select cognitive measures and single WM tracts in chronic, medicated patients. It is unclear if the cognition-WM relationship differs between antipsychotic-naïve patients with schizophrenia and healthy controls, as differential associations have not been directly examined. Here we examine if there are differential patterns of associations between cognition and WM microstructure in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls, and we characterize reliable contributors to the pattern of associations across multiple cognitive domains and WM regions, in order to elucidate white matter contribution to the neural underpinnings of cognitive deficits.

Methods: Thirty-six first-episode antipsychotic-naïve patients with schizophrenia and 52 matched healthy controls underwent cognitive tests and diffusion-weighted imaging on a 3T Magnetic Resonance Imaging scanner. Using a multivariate partial least squares correlation analysis, we included 14 cognitive variables and mean fractional anisotropy values of 48 WM regions.

Results: Initial analyses showed significant group differences in both measures of WM and cognition. There was no group interaction effect in the pattern of associations between cognition and WM microstructure. The combined analysis of patients and controls lead to a significant pattern of associations (omnibus test p = .015). Thirty-four regions and seven cognitive functions contributed reliably to the associations.

Conclusions: The lack of an interaction effect suggests similar associations in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls. This, together with the differences in both WM and cognitive measurements, supports the involvement of WM in cognitive deficits in schizophrenia. Our findings add to the field by showing a coherent picture of the overall pattern of association between cognition and WM. These findings increase our understanding of the impact of WM on cognition, contributing to the search for neuromarkers of cognitive deficits in schizophrenia.

Trial registration: ClinicalTrials.gov NCT01154829.

Keywords: CANTAB; Cognition; First-episode antipsychotic-naïve schizophrenia; Healthy controls; White matter.

Conflict of interest statement

Declaration of competing interest Dr. Ebdrup declares lecture fees from the following companies: Otsuka Pharma Scandinavia AB, Bristol-Myers Squibb, Lundbeck Pharma A/S, and Eli Lilly Denmark A/S, and has served the advisory boards of Eli Lilly Denmark A/S, Lundbeck Pharma A/S, and Takeda Pharmaceutical Company Ltd. Prof Pantelis has been part of Advisory Boards for AstraZeneca, Janssen-Cilag, Lundbeck and Servier and has received fees for presentations at seminars organized by AstraZeneca, Janssen-Cilag, Lundbeck, Eli Lilly, Pfizer, and Shire. No other competing interests or conflicts of interests declared for the other authors. PECANS was registered online at Clinicaltrials.gov (NCT01154829).

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.