White matter, cognition and psychotic-like experiences in UK Biobank.

M J Bosma,C R Buchanan,S M Lawrie,M J Adams,X Shen,H C Whalley,S R Cox,E M Tucker-Drob,T Ziermans

doi:10.1017/s0033291721004244

Abstract

Psychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, particularly if associated with distress. As PLEs have been related to alterations in both white matter and cognition, we investigated whether cognition (g-factor and processing speed) mediates the relationship between white matter and PLEs. We investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis. For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. For the smaller sample, variables whole-brain white matter network efficiency and microstructure were also derived from structural connectome data. The mediation of cognition on the relationships between white matter properties and PLEs was non-significant. However, lower gFA was associated with having PLEs in combination with distress in the full available sample (standardized β = -0.053, p = 0.011). Additionally, lower gFA/higher gMD was associated with lower g-factor (standardized β = 0.049, p < 0.001; standardized β = -0.027, p = 0.003), and partially mediated by processing speed with a proportion mediated of 7% (p = < 0.001) for gFA and 11% (p < 0.001) for gMD. We show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. Furthermore, we replicated that processing speed mediates the relationship between white matter microstructure and g-factor.

Highlights

Psychotic experiences are symptoms of clinically severe psychiatric disorders like schizophrenia, and occur in the general population with an estimated prevalence of 5– 10%, in which case they can be called psychotic-like experiences (PLEs)
We identified and excluded participants who had scores of 3.5 standard deviations above or below the group mean for all derived predicting and mediating variables
Because the direct effect and both indirect effects of the mediation model proved to be significant when tested with imaging derived phenotypes (IDPs) derived general FA (gFA) and general MD (gMD), we evaluated whether the relationship between both white matter parameters and g-factor was partially mediated by reaction time

Summary

Introduction

Psychotic experiences are symptoms of clinically severe psychiatric disorders like schizophrenia, and occur in the general population with an estimated prevalence of 5– 10%, in which case they can be called psychotic-like experiences (PLEs). Schoorl et al (2021) found a significant association between localized white matter integrity in the splenium of the corpus callosum and a specific PLE (visual hallucinatory experiences), especially when accompanied by distress. Psychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, if associated with distress. We investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. We show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. We replicated that processing speed mediates the relationship between white matter microstructure and g-factor

Methods

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Discussion

Conclusion