Journal article
Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia
- Abstract:
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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 to controls. Tract-specific heterochronicity measures, i.e., abnormal rates of adolescent maturation and aging explained ~50% of the regional variance effects of diagnosis and age-by-diagnosis interaction in patients. Interactive, 3D 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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-
(Preview, Accepted manuscript, pdf, 1.1MB, Terms of use)
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- Publisher copy:
- 10.1002/hbm.23336
Authors
- Publisher:
- Wiley
- Journal:
- Human Brain Mapping More from this journal
- Volume:
- 37
- Issue:
- 12
- Pages:
- 4673-4688
- Publication date:
- 2016-08-01
- Acceptance date:
- 2016-07-24
- DOI:
- EISSN:
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1097-0193
- ISSN:
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1065-9471
- Pmid:
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27477775
- Language:
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English
- Keywords:
- Pubs id:
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pubs:638225
- UUID:
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uuid:1d9671af-5567-443a-b82c-02cbbbbb4ba4
- Local pid:
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pubs:638225
- Source identifiers:
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638225
- Deposit date:
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2018-11-01
Terms of use
- Copyright holder:
- Wiley Periodicals, Inc
- Copyright date:
- 2016
- Notes:
- © 2016 Wiley Periodicals, Inc. This is the accepted manuscript version of the article. The final version is available online from Wiley at: https://doi.org/10.1002/hbm.23336
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