title: Alterations in white matter evident before the onset of psychosis.
abstract: BACKGROUND
  Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.
  
  
  METHODS
  Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.
  
  
  RESULTS
  At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to controls, first-episode patients showed widespread reductions in FA and increases in diffusivity. DTI indices in the UHR group were intermediate relative to those in the other 2 groups. Longitudinal analysis revealed a significant group by time interaction in the left frontal WM (P < .001). In this region, there was a progressive reduction in FA in UHR subjects who developed psychosis that was not evident in UHR subjects who did not make a transition.
  
  
  CONCLUSIONS
  People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia. The onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK. francesco.carletti@kcl.ac.uk
authors.forename: Francesco
authors.initials: F
authors.lastname: Carletti
authors.forename: James B
authors.initials: JB
authors.lastname: Woolley
authors.forename: Sagnik
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Rocio
authors.initials: R
authors.lastname: Perez-Iglesias
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar Poli
authors.forename: Lucia
authors.initials: L
authors.lastname: Valmaggia
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Broome
authors.forename: Elvira
authors.initials: E
authors.lastname: Bramon
authors.forename: Louise
authors.initials: L
authors.lastname: Johns
authors.forename: Vincent
authors.initials: V
authors.lastname: Giampietro
authors.forename: Steve C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003337:Corpus Callosum / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D062706:Prodromal Symptoms; D012559:Schizophrenia / Q000473:pathology*; D013997:Time Factors