title: A longitudinal study investigating sub-threshold symptoms and white matter changes in individuals with an 'at risk mental state' (ARMS).
abstract: BACKGROUND
  Evidence supports disruption in white matter (WM) connectivity in established schizophrenia, however, it is unclear when these abnormalities occur during the course of illness and if they are progressive. Here we investigated whether WM abnormalities predate illness onset by examining a group of individuals with an 'at risk mental state' (ARMS) and assess whether there is evidence of progressive change. We hypothesized that WM abnormalities are associated with symptom change.
  
  
  METHODS
  Sixteen healthy controls and 41 ARMS subjects at baseline underwent Diffusion Tensor Imaging (DTI). Sub-threshold positive symptoms were measured using the Scale of Prodromal Symptoms (SOPS). Imaging and symptoms were re-administered in the ARMS group after one year (52weeks). Fractional anisotropy (FA) value differences between ARMS and control groups at baseline were localized using the method of Tract-Based Spatial Statistics (TBSS).
  
  
  RESULTS
  At baseline, FA was significantly reduced in a sub-region of the corpus callosum (CC) in the ARMS group as a whole compared to controls. This reduction was also found in the 34 individuals who did not transition (ARMS-N) during the one-year follow-up. However, the ARMS-N group showed a significant improvement in sub-threshold positive symptoms at follow-up, which was correlated with an increase in FA in the same CC region (r=-0.664, p<0.001).
  
  
  CONCLUSIONS
  There was a significant FA reduction in the CC in individuals at high risk for psychosis regardless of transition status at one year. This suggests that WM abnormalities in the CC may represent a biological vulnerability to psychosis. Improvement in sub-threshold positive symptoms was associated with improvement in measures of WM integrity in the CC. This may suggest that neurobiological 'resilience' is associated with improved outcomes, although this notion requires future study.
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan; Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Melbourne, Australia.
authors: Naoyuki
authors: N
authors: Katagiri
authors: Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Melbourne, Australia.
authors: Christos
authors: C
authors: Pantelis
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan. Electronic address: takahiro.nemoto@med.toho-u.ac.jp.
authors: Takahiro
authors: T
authors: Nemoto
authors: Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Melbourne, Australia; Melbourne School of Engineering, The University of Melbourne, Melbourne, Australia.
authors: Andrew
authors: A
authors: Zalesky
authors: Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Masaaki
authors: M
authors: Hori
authors: Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Diagnostic Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors: Keigo
authors: K
authors: Shimoji
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
authors: Junichi
authors: J
authors: Saito
authors: Department of Social Medicine, Toho University School of Medicine, Tokyo, Japan.
authors: Shinya
authors: S
authors: Ito
authors: Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Melbourne, Australia.
authors: Dominic B
authors: DB
authors: Dwyer
authors: Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Issei
authors: I
authors: Fukunaga
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
authors: Keiko
authors: K
authors: Morita
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
authors: Naohisa
authors: N
authors: Tsujino
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
authors: Taiju
authors: T
authors: Yamaguchi
authors: Department of Radiology, Toho University School of Medicine, Tokyo, Japan.
authors: Nobuyuki
authors: N
authors: Shiraga
authors: Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Shigeki
authors: S
authors: Aoki
authors: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
authors: Masafumi
authors: M
authors: Mizuno
mesh_terms: D000328:Adult; D000367:Age Factors; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D062706:Prodromal Symptoms; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000473:pathology*; D012044:Regression Analysis; D012737:Sex Factors; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: At risk mental state; Corpus callosum; Diffusion tensor imaging; Prodrome; Psychosis; White matter integrity