Open AccessHeterochronicity of white matter development and aging explains regional patient control differences in schizophrenia
Author(s) -
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
Publication year - 2016
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.23336
Subject(s) - white matter , schizophrenia (object oriented programming) , fractional anisotropy , diffusion mri , psychology , analysis of variance , neuroscience , medicine , magnetic resonance imaging , psychiatry , radiology
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.