The shape of things to come. Mapping spatiotemporal progression of striatal morphology in Huntington disease: The IMAGE-HD study

Fiona A Wilkes; David Jakabek; Mark Walterfang; Dennis Velakoulis; Govinda R Poudel; Julie C Stout; Phyllis Chua; Gary F Egan; Jeffrey C L Looi; Nellie Georgiou-Karistianis

doi:10.1016/j.pscychresns.2023.111717

The shape of things to come. Mapping spatiotemporal progression of striatal morphology in Huntington disease: The IMAGE-HD study

Psychiatry Res Neuroimaging. 2023 Oct:335:111717. doi: 10.1016/j.pscychresns.2023.111717. Epub 2023 Sep 14.

Authors

Affiliations

¹ Research Centre for the Neurosciences of Ageing, Academic Unit of Psychiatry and Addiction Medicine, Australian National University Medical School, Canberra Hospital, Canberra, Australia. Electronic address: [email protected].
² Neuroscience Research Australia, Sydney, Australia.
³ Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne Neuropsychiatry Centre, University of Melbourne and Northwestern Mental Health, Melbourne, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
⁴ Mary Mackillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
⁵ School of Psychological Sciences and the Turner Institute of Brain and Mental Health, Monash University, Melbourne, Australia.
⁶ Department of Psychiatry, School of Clinical Sciences, Monash University, Monash Medical Centre, Melbourne, Australia.
⁷ Research Centre for the Neurosciences of Ageing, Academic Unit of Psychiatry and Addiction Medicine, Australian National University Medical School, Canberra Hospital, Canberra, Australia; Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne Neuropsychiatry Centre, University of Melbourne and Northwestern Mental Health, Melbourne, Australia.

PMID: 37751638
DOI: 10.1016/j.pscychresns.2023.111717

Abstract

Mapping the spatiotemporal progression of neuroanatomical change in Huntington's Disease (HD) is fundamental to the development of bio-measures for prognostication. Statistical shape analysis to measure the striatum has been performed in HD, however there have been a limited number of longitudinal studies. To address these limitations, we utilised the Spherical Harmonic Point Distribution Method (SPHARM-PDM) to generate point distribution models of the striatum in individuals, and used linear mixed models to test for localised shape change over time in pre-manifest HD (pre-HD), symp-HD (symp-HD) and control individuals. Longitudinal MRI scans from the IMAGE-HD study were used (baseline, 18 and 30 months). We found significant differences in the shape of the striatum between groups. Significant group-by-time interaction was observed for the putamen bilaterally, but not for caudate. A differential rate of shape change between groups over time was observed, with more significant deflation in the symp-HD group in comparison with the pre-HD and control groups. CAG repeats were correlated with bilateral striatal shape in pre-HD and symp-HD. Robust statistical analysis of the correlates of striatal shape change in HD has confirmed the suitability of striatal morphology as a potential biomarker correlated with CAG-repeat length, and potentially, an endophenotype.

Keywords: Biomarker; Endophenotype; Huntington's disease; Striatum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Corpus Striatum / diagnostic imaging
Humans
Huntington Disease* / diagnostic imaging
Huntington Disease* / genetics
Longitudinal Studies
Magnetic Resonance Imaging / methods
Putamen