title: Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.
abstract: Altered brain connectivity is implicated in the development and clinical burden of schizophrenia. Relative to matched controls, schizophrenia patients show (1) a global and regional reduction in the integrity of the brain's white matter (WM), assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA), and (2) accelerated age-related decline in FA values. In the largest mega-analysis to date, we tested if differences in the trajectories of WM tract development influenced patient-control differences in FA. We also assessed if specific tracts showed exacerbated decline with aging.
  
  
  
  Three cohorts of schizophrenia patients (total n = 177) and controls (total n = 249; age = 18-61 years) were ascertained with three 3T Siemens MRI scanners. Whole-brain and regional FA values were extracted using ENIGMA-DTI protocols. Statistics were evaluated using mega- and meta-analyses to detect effects of diagnosis and age-by-diagnosis interactions.
  
  
  
  In mega-analysis of whole-brain averaged FA, schizophrenia patients had lower FA (P = 10-11) and faster age-related decline in FA (P = 0.02) compared with controls. Tract-specific heterochronicity measures, that is, abnormal rates of adolescent maturation and aging explained approximately 50% of the regional variance effects of diagnosis and age-by-diagnosis interaction in patients. Interactive, three-dimensional visualization of the results is available at www.enigma-viewer.org.
  
  
  
  WM tracts that mature later in life appeared more sensitive to the pathophysiology of schizophrenia and were more susceptible to faster age-related decline in FA values. Hum Brain Mapp 37:4673-4688, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Department of Statistics, University of Warwick, Warwick, United Kingdom.
authors.forename: Habib
authors.initials: H
authors.lastname: Ganjgahi
authors.affiliation: FMRIB Centre, Oxford University, Oxford, United Kingdom.
authors.forename: Anderson
authors.identifier: 0000-0002-4169-9781
authors.initials: A
authors.lastname: Winkler
authors.affiliation: Imaging Genetics Center, Keck School of Medicine of USC, Marina del Rey, California.
authors.forename: Sinead
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Shukla
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
authors.affiliation: Imaging Genetics Center, Keck School of Medicine of USC, Marina del Rey, California.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rowland
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Sampath
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Binish
authors.initials: B
authors.lastname: Patel
authors.affiliation: Neuroscience Research Unit, Worldwide Research and Development, Pfizer Inc, 610 Main Street, Cambridge, Massachusetts, 02139.
authors.forename: Patricio
authors.initials: P
authors.lastname: O'Donnell
authors.affiliation: Neuroscience Research Unit, Worldwide Research and Development, Pfizer Inc, 610 Main Street, Cambridge, Massachusetts, 02139.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Enterprise Scientific Technology Operations, Worldwide Research and Development, Pfizer Inc, Eastern Point Rd, Groton, Connecticut, 06340.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Paciga
authors.affiliation: Enterprise Scientific Technology Operations, Worldwide Research and Development, Pfizer Inc, Eastern Point Rd, Groton, Connecticut, 06340.|Biogen, Cambridge, Massachusetts, 02142.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Schubert
authors.affiliation: Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, Maryland, 21250.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, Maryland, 21250.
authors.forename: Guohao
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Imaging Genetics Center, Keck School of Medicine of USC, Marina del Rey, California.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Statistics, University of Warwick, Warwick, United Kingdom.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nichols
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging* / Q000254:growth & development*; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000000981:diagnostic imaging*; D066127:White Matter / Q000000981:diagnostic imaging* / Q000254:growth & development*; D055815:Young Adult
keywords: DTI; aging; schizophrenia