| Summary: | <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>
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