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Deficits in neurite density underlie white matter structure abnormalities in first-episode psychosis

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Version 2 2023-06-12, 08:38
Version 1 2023-06-09, 05:08
journal contribution
posted on 2023-06-12, 08:38 authored by Charlotte RaeCharlotte Rae, Geoff Davies, Sarah Garfinkel, Matthew Gabel, Nicholas DowellNicholas Dowell, Mara Cercignani, Anil SethAnil Seth, Kathryn GreenwoodKathryn Greenwood, Nick Medford, Hugo CritchleyHugo Critchley
Background: Structural abnormalities across multiple white matter tracts are recognised in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterise microstructural white matter abnormalities for a deeper understanding of the developmental aetiology of psychosis. Methods: Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using Neurite Orientation Dispersion and Density Imaging (NODDI), a multi-shell diffusion-weighted MRI technique that distinguishes white matter fibre arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and controls and tested associations with age, symptom severity and medication. Results: Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fibre bundle arrangement (orientation dispersion index). There was no direct relationship with active symptomatology. FA decreased and orientation dispersion index increased with age in patients, but not controls, suggesting accelerated effects of white matter geometry change. Conclusions: Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of NODDI in psychosis, we found that processes compromising axonal fibre number, density, and myelination, rather than processes leading to spatial disruption of fibre organisation, are implicated in the aetiology of the disorder. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis.

Funding

The Sackler Centre Donation; G0318; SACKLER-DR MORTIMER AND THERESA SACKLER FOUNDATION

History

Publication status

  • Published

File Version

  • Published version

Journal

Biological Psychiatry

ISSN

0006-3223

Publisher

Elsevier

Issue

10

Volume

82

Page range

716-725

Department affiliated with

  • BSMS Neuroscience Publications

Research groups affiliated with

  • Sackler Centre for Consciousness Science Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-02-13

First Open Access (FOA) Date

2017-05-12

First Compliant Deposit (FCD) Date

2017-02-13

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