title: Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.
abstract: BACKGROUND
  Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology 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, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber 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 control subjects 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 fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, 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 neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis.
authors.affiliation: Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton; Division of Neuroscience, University of Sussex, Falmer, Brighton. Electronic address: c.rae@bsms.ac.uk.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Rae
authors.affiliation: Brighton & Sussex Medical School, School of Psychology, University of Sussex, Falmer, Brighton; Sussex Partnership National Health Service Foundation Trust, United Kingdom.
authors.forename: Geoff
authors.initials: G
authors.lastname: Davies
authors.affiliation: Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton; Division of Neuroscience, University of Sussex, Falmer, Brighton.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Garfinkel
authors.affiliation: Division of Neuroscience, University of Sussex, Falmer, Brighton.
authors.forename: Matt C
authors.initials: MC
authors.lastname: Gabel
authors.affiliation: Division of Neuroscience, University of Sussex, Falmer, Brighton.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Dowell
authors.affiliation: Division of Neuroscience, University of Sussex, Falmer, Brighton.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.affiliation: Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton; School of Engineering & Informatics, University of Sussex, Falmer, Brighton.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Seth
authors.affiliation: Brighton & Sussex Medical School, School of Psychology, University of Sussex, Falmer, Brighton; Sussex Partnership National Health Service Foundation Trust, United Kingdom.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Greenwood
authors.affiliation: Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton; Division of Neuroscience, University of Sussex, Falmer, Brighton; Sussex Partnership National Health Service Foundation Trust, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Medford
authors.affiliation: Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton; Division of Neuroscience, University of Sussex, Falmer, Brighton; Sussex Partnership National Health Service Foundation Trust, United Kingdom.
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Critchley
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016880:Anisotropy; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D016022:Case-Control Studies; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000473:pathology; D016501:Neurites / Q000473:pathology*; D059906:Neuroimaging; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: Diffusion MRI; First-episode psychosis; Fractional anisotropy; Neurite density; Neurite orientation dispersion and density imaging (NODDI); White matter microstructure