Psychotic‐like experiences and white matter microstructure: A fixel‐based analysis approach with robust replication across two cohorts
Autor(in); Institution
Goodwin, Isabella; Melbourne School of Psychological Sciences, The University of Melbourne Melbourne, AUSTRALIA
Larsen, Kit Melissa; Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine Copenhagen University Hospital Copenhagen, DENMARK
Sangchooli, Arshiya; Melbourne School of Psychological Sciences, The University of Melbourne Melbourne, AUSTRALIA; Turner Institute for Brain and Mental Health, Monash University, Clayton VIC, AUSTRALIA
Smith, Robert E.; Florey Department of Neuroscience and Mental Health The University of Melbourne Melbourne, AUSTRALIA
Banaschewski, Tobias; Department of Child and Adolescent Psychiatry and Psychotherapy Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, German Center for Mental Health (DZPG) Mannheim, GERMANY
Barker, Gareth J.; Department of Neuroimaging Institute of Psychiatry, Psychology & Neuroscience London, UK
Bokde, Arun L. W.; Discipline of Psychiatry School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin Dublin, IRELAND
Desrivières, Sylvane; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, UK
Garavan, Hugh; Department of Psychiatry and Psychology University of Vermont Burlington, USA
Gowland, Penny; Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, UK
Grigis, Antoine; NeuroSpin, CEA, Gif-sur-Yvette, FRANCE
Heinz, Andreas; Department of Psychiatry and Psychotherapy CCM Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin, GERMANY
Lemaitre, Herve; Institut Des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, Bordeaux, FRANCE
Martinot, Jean‐Luc; Institut National de la Santé et de la Recherce Médicale, INSERM U A10 “Trajectoires développementales & Psychiatrie”, University Paris, u8208 Saclay, Ecole Normale Supérieure Paris, 8208 Saclay, CNRS Gif-sur-Yvette, FRANCE
Martinot, Marie‐Laure Paillère; AP-HP. Sorbonne Université, Department of C Sorbonne Université, Department of Child and Adolescent Psychiatry Pitié, 8208 Salpêtrière Hospital Paris, FRANCE
Artiges, Eric; Psychiatry Department EPS Barthélémy Durand Etampes, FRANCE; Institut National de la Santé et de la Recherce Médicale, INSERM U A10 "Trajectoires développementales & Psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Gif-sur-Yvette, FRANCE
Nees, Frauke; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, GERMANY
Orfanos, Dimitri Papadopoulos; Department of Psychology School of Social Sciences, University of Mannheim Mannheim, GERMANY
Paus, Tomáš; Department of Psychiatry McGill University, Montreal, CANADA
Poustka, Luise; Department of Child and Adolescent Psychiatry Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, GERMANY
Smolka, Michael N.; Department of Psychiatry and Psychotherapy Technische Universität Dresden, Dresden, GERMANY
Vaidya, Nilakshi; Centre for Population Neuroscience and Stratified Medicine (PONS), department of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin, Berlin, GERMANY
Walter, Henrik; Department of Psychiatry and Psychotherapy CCM Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GERMANY
Whelan, Robert; School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, IRELAND
Schumann, Gunter; Centre for Population Neuroscience and Precision Medicine (PONS), Institute for Science and Technology of Brain Inspired Intelligence (ISTBI), Fudan University, Shanghai, CHINA; Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, GERMANY
Hester, Robert; Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, AUSTRALIA
Garrido, Marta I.; Graeme Clark Institute for Biomedical Engineering The University of Melbourne, Melbourne, AUSTRALIA; Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, AUSTRALIA
Structural deficits in white matter fibre have been linked to psychosis. However, it remains unclear whether these aberrations are present in individuals that experience non-clinical psychotic-like experiences, predating illness onset. While previous research demonstrates that alterations in white matter in schizotypy are consistent with those in clinical psychosis, these studies often dichotomise healthy samples into high and low schizotypy, which may reduce statistical sensitivity. Previous research is also confounded by the investigation of diffusion MRI parameters that fail to account for complex crossing fibre populations. In this work, we treat psychotic-like experiences as a continuous variable, and applied Fixel-Based Analysis (FBA), a framework for investigating microstructural and morphological effects in brain white matter using diffusion-weighted imaging data. Across two independent cohorts of healthy participants with varied psychotic-like experiences including data from the IMAGEN consortium (Study 1 n = 41; Study 2 n = 1098), we hypothesized that greater psychotic-like experiences would be associated with FBA metrics sensitive to microstructural fibre density and/or cross-sectional morphological effects. Contrary to our hypothesis, we did not find significant correlations between psychotic-like experiences and FBA metrics across either dataset (FWE p < 0.05). Bayesian analysis of tract-aggregated data showed substantial evidence of no association (Bayes factor < 1/3) between psychotic-like experiences and fibre density, nor cross-sectional morphology, across several white matter tracts of interest, pre-defined from prior neuroimaging literature. These findings suggest that the relationship between non-clinical psychotic-like experiences and white matter microstructure may not be as robust as previously thought. This raises the possibility that white matter alterations across the psychosis spectrum echo clinical diagnostic thresholding, with observable effects in clinical but not sub-clinical presentations. Our findings show no association between whole-brain fibre-specific properties of white matter microstructure and sub-clinical psychotic-like experiences. Further, we show evidence for the lack of an association within tract-aggregated fibre-specific metrics. Future research should integrate longitudinal designs to explore whether fibre-specific white matter attributes provide clinically meaningful insight into the risk of psychosis onset.
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Rechteinformation
CC BY 4.0 ; Creative Commons Attribution 4.0 License
Förderinformationen (1)
Förderername: Lundbeck Foundation
Förderinformationen (2)
Förderername: National Imaging Facility
Förderinformationen (3)
Förderername: Centre of Excellence for Integrative Brain Function, Australian Research Council
Zitierung
Goodwin, I., Larsen, K. M., Sangchooli, A., Smith, R. E., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Brühl, R., Desrivières, S., Garavan, H., Gowland, P., Grigis, A., Heinz, A., Lemaitre, H., Martinot, J., Martinot, M. P., Artiges, E., Nees, F., Orfanos, D. P., Paus, T., Poustka, L., Smolka, M. N., Vaidya, N., Walter, H., Whelan, R., Schumann, G., Hester, R., & Garrido, M. I. (2025). Psychotic‐like experiences and white matter microstructure: A fixel‐based analysis approach with robust replication across two cohorts. Human Brain Mapping, 46(17), 1–14. https://doi.org/10.1002/hbm.70414
