School of Medicine Publications and Presentations
Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia
Document Type
Article
Publication Date
12-1-2016
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 http://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.
Recommended Citation
Kochunov, P., Ganjgahi, H., Winkler, A., Kelly, S., Shukla, D. K., Du, X., Jahanshad, N., Rowland, L., Sampath, H., Patel, B., O'Donnell, P., Xie, Z., Paciga, S. A., Schubert, C. R., Chen, J., Zhang, G., Thompson, P. M., Nichols, T. E., & Hong, L. E. (2016). Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia. Human brain mapping, 37(12), 4673–4688. https://doi.org/10.1002/hbm.23336
First Page
4673
Last Page
4688
Publication Title
Human brain mapping
DOI
10.1002/hbm.23336
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright © 2016 Wiley Periodicals, Inc.