title: White matter microstructure in individuals at clinical high risk of psychosis: a whole-brain diffusion tensor imaging study.
abstract: BACKGROUND
  The study of individuals at clinical high risk (CHR) for psychosis provides an important opportunity for unraveling pathological mechanisms underlying schizophrenia and related disorders. A small number of diffusion tensor magnetic resonance imaging (DTI) studies in CHR samples have yielded anatomically inconsistent results. The present study is the first to apply tract-based spatial statistics (TBSS) to perform a whole-brain DTI analysis in CHR subjects.
  
  
  METHODS
  A total of 28 individuals meeting CHR criteria and 34 healthy controls underwent DTI. TBSS was used for a group comparison of fractional anisotropy (FA), as well as axial, radial, and mean diffusivity (AD, RD, and MD). Conversion to psychosis was monitored during a mean follow-up period of 12.3 months.
  
  
  RESULTS
  The rate of conversion to psychosis was relatively low (4%). TBSS revealed increased MD in several clusters in the right hemisphere, most notably in the superior longitudinal fasciculus (SLF), posterior corona radiata, and corpus callosum (splenium and body). Increased RD was restricted to a smaller area in the posterior parietal lobe.
  
  
  CONCLUSIONS
  We present further evidence that white matter microstructure is abnormal in CHR individuals, even in a sample in which the vast majority do not transition to psychosis over the following year. In accord with previous studies on CHR individuals and patients with early-onset schizophrenia, our findings suggest an important pathological role for the parietal lobe and especially the SLF. The latter is known to undergo particularly dynamic microstructural changes during adolescence and early adulthood, a critical phase for the development of psychotic illness.
authors.affiliation: clemm@bwh.harvard.edu.
authors.forename: Christian Clemm
authors.initials: CC
authors.lastname: von Hohenberg
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA;
authors.forename: Ofer
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA; Department of Radiology, Harvard Medical School, Boston, MA;
authors.forename: Marek
authors.initials: M
authors.lastname: Kubicki
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Thomas
authors.initials: T
authors.lastname: Ballinger
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Mai-Anh
authors.initials: MA
authors.lastname: Vu
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Tali
authors.initials: T
authors.lastname: Swisher
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Katie
authors.initials: K
authors.lastname: Green
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Michelle
authors.initials: M
authors.lastname: Giwerc
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Brian
authors.initials: B
authors.lastname: Dahlben
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA; Departments of Psychiatry and Medicine, Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Jill M
authors.initials: JM
authors.lastname: Goldstein
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA;
authors.forename: Tsung-Ung W
authors.initials: TU
authors.lastname: Woo
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA; Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA;
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Petryshen
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA; Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
authors.forename: Raquelle I
authors.initials: RI
authors.lastname: Mesholam-Gately
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA; Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Woodberry
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA;
authors.forename: Heidi W
authors.initials: HW
authors.lastname: Thermenos
authors.affiliation: Psychiatry Neuroimaging Branch, Imaging Center NeuroImage Nord and Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Mulert
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA; Clinical Neuroscience Division, Laboratory of Neuroscience, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA;
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA; Department of Radiology, Harvard Medical School, Boston, MA; Clinical Neuroscience Division, Laboratory of Neuroscience, Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003337:Corpus Callosum / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D010296:Parietal Lobe / Q000473:pathology*; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000473:pathology*; D012306:Risk; D012559:Schizophrenia / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: TBSS; diffusivity; mean; parietal lobe; prodrome; radial; schizophrenia