Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia
<h4>Background</h4> <p>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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2016
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| _version_ | 1797057097694707712 |
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| author | Kochunov, P Ganjgahi, H Winkler, A Kelly, S Shukla, DK Du, X Jahanshad, N Rowland, L Sampath, H Patel, B O'Donnell, P Xie, Z Paciga, SA Schubert, CR Chen, J Zhang, G Thompson, PM Nichols, TE Hong, LE |
| author_facet | Kochunov, P Ganjgahi, H Winkler, A Kelly, S Shukla, DK Du, X Jahanshad, N Rowland, L Sampath, H Patel, B O'Donnell, P Xie, Z Paciga, SA Schubert, CR Chen, J Zhang, G Thompson, PM Nichols, TE Hong, LE |
| author_sort | Kochunov, P |
| collection | OXFORD |
| description | <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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.</p> <h4>Conclusion</h4> <p>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.</p> |
| first_indexed | 2024-03-06T19:31:26Z |
| format | Journal article |
| id | oxford-uuid:1d9671af-5567-443a-b82c-02cbbbbb4ba4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:31:26Z |
| publishDate | 2016 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:1d9671af-5567-443a-b82c-02cbbbbb4ba42022-03-26T11:11:49ZHeterochronicity of white matter development and aging explains regional patient control differences in schizophreniaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d9671af-5567-443a-b82c-02cbbbbb4ba4EnglishSymplectic Elements at OxfordWiley2016Kochunov, PGanjgahi, HWinkler, AKelly, SShukla, DKDu, XJahanshad, NRowland, LSampath, HPatel, BO'Donnell, PXie, ZPaciga, SASchubert, CRChen, JZhang, GThompson, PMNichols, TEHong, LE <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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.</p> <h4>Conclusion</h4> <p>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.</p> |
| spellingShingle | Kochunov, P Ganjgahi, H Winkler, A Kelly, S Shukla, DK Du, X Jahanshad, N Rowland, L Sampath, H Patel, B O'Donnell, P Xie, Z Paciga, SA Schubert, CR Chen, J Zhang, G Thompson, PM Nichols, TE Hong, LE Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
| title | Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
| title_full | Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
| title_fullStr | Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
| title_full_unstemmed | Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
| title_short | Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
| title_sort | heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia |
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