Format

Send to

Choose Destination
Hum Brain Mapp. 2016 Dec;37(12):4673-4688. doi: 10.1002/hbm.23336. Epub 2016 Aug 1.

Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.

Author information

1
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
2
Department of Statistics, University of Warwick, Warwick, United Kingdom.
3
FMRIB Centre, Oxford University, Oxford, United Kingdom.
4
Imaging Genetics Center, Keck School of Medicine of USC, Marina del Rey, California.
5
Neuroscience Research Unit, Worldwide Research and Development, Pfizer Inc, 610 Main Street, Cambridge, Massachusetts, 02139.
6
Enterprise Scientific Technology Operations, Worldwide Research and Development, Pfizer Inc, Eastern Point Rd, Groton, Connecticut, 06340.
7
Biogen, Cambridge, Massachusetts, 02142.
8
Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, Maryland, 21250.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

DTI; aging; schizophrenia

PMID:
27477775
PMCID:
PMC5118078
DOI:
10.1002/hbm.23336
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center