Johanna Seitz1, Jessica X Zuo2, Amanda E Lyall3, Nikos Makris4, Zora Kikinis2, Sylvain Bouix3, Ofer Pasternak5, Eli Fredman2, Jonathan Duskin2, Jill M Goldstein6, Tracey L Petryshen7, Raquelle I Mesholam-Gately8, Joanne Wojcik8, Robert W McCarley9, Larry J Seidman10, Martha E Shenton11, Inga K Koerte1, Marek Kubicki12. 1. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany; 2. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 3. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 4. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; 5. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 6. Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Department of Medicine, Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 7. Department of Psychiatry and Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetic Unit, Massachusetts General Hospital, Boston, MA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA; 8. Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; 9. Department of Psychiatry, Laboratory of Neuroscience, Clinical Neuroscience Division, VA Boston Healthcare System, Brockton, MA; 10. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; 11. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; VA Boston Healthcare System, Brockton Division, Brockton, MA. 12. Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; kubicki@bwh.harvard.edu.
Abstract
PURPOSE: Tractography is the most anatomically accurate method for delineating white matter tracts in the brain, yet few studies have examined multiple tracts using tractography in patients with schizophrenia (SCZ). We analyze 5 white matter connections important in the pathophysiology of SCZ: uncinate fasciculus, cingulum bundle (CB), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus, and arcuate fasciculus (AF). Additionally, we investigate the relationship between diffusion tensor imaging (DTI) markers and neuropsychological measures. METHODS: High-resolution DTI data were acquired on a 3 Tesla scanner in 30 patients with early-course SCZ and 30 healthy controls (HC) from the Boston Center for Intervention Development and Applied Research study. After manually guided tracts delineation, fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD) were calculated and averaged along each tract. The association of DTI measures with the Scales for the Assessment of Negative and Positive Symptoms and neuropsychological measures was evaluated. RESULTS: Compared to HC, patients exhibited reduced FA and increased trace and RD in the right AF, CB, and ILF. A discriminant analysis showed the possible use of FA of these tracts for better future group membership classifications. FA and RD of the right ILF and AF were associated with positive symptoms while FA and RD of the right CB were associated with memory performance and processing speed. CONCLUSION: We observed white matter alterations in the right CB, ILF, and AF, possibly caused by myelin disruptions. The structural abnormalities interact with cognitive performance, and are linked to clinical symptoms.
PURPOSE: Tractography is the most anatomically accurate method for delineating white matter tracts in the brain, yet few studies have examined multiple tracts using tractography in patients with schizophrenia (SCZ). We analyze 5 white matter connections important in the pathophysiology of SCZ: uncinate fasciculus, cingulum bundle (CB), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus, and arcuate fasciculus (AF). Additionally, we investigate the relationship between diffusion tensor imaging (DTI) markers and neuropsychological measures. METHODS: High-resolution DTI data were acquired on a 3 Tesla scanner in 30 patients with early-course SCZ and 30 healthy controls (HC) from the Boston Center for Intervention Development and Applied Research study. After manually guided tracts delineation, fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD) were calculated and averaged along each tract. The association of DTI measures with the Scales for the Assessment of Negative and Positive Symptoms and neuropsychological measures was evaluated. RESULTS: Compared to HC, patients exhibited reduced FA and increased trace and RD in the right AF, CB, and ILF. A discriminant analysis showed the possible use of FA of these tracts for better future group membership classifications. FA and RD of the right ILF and AF were associated with positive symptoms while FA and RD of the right CB were associated with memory performance and processing speed. CONCLUSION: We observed white matter alterations in the right CB, ILF, and AF, possibly caused by myelin disruptions. The structural abnormalities interact with cognitive performance, and are linked to clinical symptoms.
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