Psychotic-like experiences and white matter microstructure: A fixel-based analysis approach
Poster No:
1290
Submission Type:
Abstract Submission
Authors:
Isabella Goodwin1, Kit Melissa Larsen2, Arshiya Sangchooli1,3, Robert Smith4,5, Robert Hester1, Marta Garrido1,6
Institutions:
1Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Australia, 2Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Copenhagen, Denmark, 3Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia, 4The Florey Institute of Neuroscience and Mental Health, Heidleberg, Australia, 5Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia, 6Graeme Clark Institute for Biomedical Engineering, The University of Melbourne, Melbourne, Australia
First Author:
Isabella Goodwin
Melbourne School of Psychological Sciences, The University of Melbourne
Melbourne, Australia
Melbourne School of Psychological Sciences, The University of Melbourne
Melbourne, Australia
Co-Author(s):
Kit Melissa Larsen
Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital
Copenhagen, Denmark
Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital
Copenhagen, Denmark
Arshiya Sangchooli
Melbourne School of Psychological Sciences, The University of Melbourne|Turner Institute for Brain and Mental Health, Monash University
Melbourne, Australia|Melbourne, Australia
Melbourne School of Psychological Sciences, The University of Melbourne|Turner Institute for Brain and Mental Health, Monash University
Melbourne, Australia|Melbourne, Australia
Robert Smith
The Florey Institute of Neuroscience and Mental Health|Florey Department of Neuroscience and Mental Health, The University of Melbourne
Heidleberg, Australia|Melbourne, Australia
The Florey Institute of Neuroscience and Mental Health|Florey Department of Neuroscience and Mental Health, The University of Melbourne
Heidleberg, Australia|Melbourne, Australia
Robert Hester
Melbourne School of Psychological Sciences, The University of Melbourne
Melbourne, Australia
Melbourne School of Psychological Sciences, The University of Melbourne
Melbourne, Australia
Marta Garrido
Melbourne School of Psychological Sciences, The University of Melbourne|Graeme Clark Institute for Biomedical Engineering, The University of Melbourne
Melbourne, Australia|Melbourne, Australia
Melbourne School of Psychological Sciences, The University of Melbourne|Graeme Clark Institute for Biomedical Engineering, The University of Melbourne
Melbourne, Australia|Melbourne, Australia
Introduction:
Structural deficits in white matter fibres have been linked to psychosis (Karlsgodt, 2020). However, it remains unclear whether these aberrations are present in non-clinical psychotic-like experiences, predating illness onset. Previous research demonstrated that alterations in white matter in schizotypy are consistent with those in clinical psychosis (Bosma et al., 2021; DeRosse et al., 2015; Nelson et al., 2011; Schoorl et al., 2021). However, past studies dichotomised healthy samples into high and low schizotypy, used outdated analysis techniques, and are confounded by small sample sizes with a lack of replicability. Here, we treated this phenotype as a dimensional scale, used continuous analyses to account for individual differences in psychotic-like experiences, and applied Fixel-Based Analysis (FBA) (Raffelt et al., 2015, 2017), a state-of-the-art framework for investigating white matter using diffusion-weighted imaging data.
Methods:
We performed FBA in two cohorts of healthy participants with varied psychotic-like experiences. In the first cohort (study 1), 41 participants were selectively sampled across a uniform distribution of psychotic-like experiences, addressing a limitation in previous research. Replication in the second cohort (study 2), consisting of 1,098 participants from the IMAGEN consortium, provided greater power and a larger population-based distribution in psychotic-like experiences. Across both cohorts, we hypothesized that greater psychotic-like experiences would negatively correlate with FBA metrics sensitive to microstructural fibre density and/or cross-sectional morphological effects.
·Figure 1. Schematic summarizing key steps of FBA analysis pipeline, highlighting differences between study 1 and study 2
Results:
Contrary to our hypothesis, we found no significant correlations between psychotic-like experiences and FBA metrics when adjusting for age, sex, and intracranial volume, for either whole-brain or tract-specific analyses, in either dataset (family-wise error control p > 0.05, applied individually to each hypothesis). Bayesian analysis of tract-aggregated data showed substantial evidence of no association between psychotic-like experiences and fibre density (Bayes factor <1/3) across several pre-defined white matter tracts including the cingulum gyrus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus.
Conclusions:
The relationship between psychotic-like experiences and white matter microstructure may not be as robust as previously thought, given that no such relationship was observed when applying advanced analysis techniques that address limitations of traditional voxel-based methods. This raises the possibility that white matter alterations in clinical psychosis represent diagnostic thresholding, with no observable effect in sub-clinical presentations. Our replication methodology provides robust, valuable insight into the nuances of white matter structure and psychotic-like experiences. Future research should integrate longitudinal designs to determine whether white matter measures can predict progression from sub-clinical to clinical psychosis.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
Bayesian Modeling
Diffusion MRI Modeling and Analysis 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Novel Imaging Acquisition Methods:
Diffusion MRI
Keywords:
White Matter
Other - Diffusion-weighted imaging; Psychotic-like experiences; Fixel-based analysis
1|2Indicates the priority used for review
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2. DeRosse, P., Nitzburg, G. C., Ikuta, T., Peters, B. D., Malhotra, A. K., & Szeszko, P. R. (2015). Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy. Schizophrenia Bulletin, 41(1), 104–114. https://doi.org/10.1093/schbul/sbu150
3. Karlsgodt, K. H. (2020). White Matter Microstructure across the Psychosis Spectrum. Trends in Neurosciences, 43(6), 406–416. https://doi.org/10.1016/j.tins.2020.03.014
4. Nelson, M. T., Seal, M. L., Phillips, L. J., Merritt, A. H., Wilson, R., & Pantelis, C. (2011). An Investigation of the Relationship Between Cortical Connectivity and Schizotypy in the General Population. The Journal of Nervous and Mental Disease, 199(5), 348–353. https://doi.org/10.1097/NMD.0b013e318217514b
5. Raffelt, D. A., Smith, R. E., Ridgway, G. R., Tournier, J.-D., Vaughan, D. N., Rose, S., Henderson, R., & Connelly, A. (2015). Connectivity-based fixel enhancement: Whole-brain statistical analysis of diffusion MRI measures in the presence of crossing fibres. NeuroImage, 117, 40–55. https://doi.org/10.1016/j.neuroimage.2015.05.039
6. Raffelt, D. A., Tournier, J.-D., Smith, R. E., Vaughan, D. N., Jackson, G., Ridgway, G. R., & Connelly, A. (2017). Investigating white matter fibre density and morphology using fixel-based analysis. NeuroImage, 144(Pt A), 58–73. https://doi.org/10.1016/j.neuroimage.2016.09.029
7. Schoorl, J., Barbu, M. C., Shen, X., Harris, M. R., Adams, M. J., Whalley, H. C., & Lawrie, S. M. (2021). Grey and white matter associations of psychotic-like experiences in a general population sample (UK Biobank). Translational Psychiatry, 11(1), Article 1. https://doi.org/10.1038/s41398-020-01131-7