학술논문
Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.
Document Type
Article
Author
Kochunov, Peter; Ganjgahi, Habib; Winkler, Anderson; Kelly, Sinead; Shukla, Dinesh K.; Du, Xiaoming; Jahanshad, Neda; Rowland, Laura; Sampath, Hemalatha; Patel, Binish; O'Donnell, Patricio; Xie, Zhiyong; Paciga, Sara A.; Schubert, Christian R.; Chen, Jian; Zhang, Guohao; Thompson, Paul M.; Nichols, Thomas E.; Hong, L. Elliot
Source
Subject
Language
ISSN
1065-9471
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 . 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. [ABSTRACT FROM AUTHOR]