title: Primary and secondary alterations of white matter connectivity in schizophrenia: A study on first-episode and chronic patients using whole-brain tractography-based analysis.
abstract: Schizophrenia is a debilitating mental disorder that is associated with an impaired connection of cerebral white matter. Studies on patients with chronic and first-episode schizophrenia have found widespread white matter abnormalities. However, it is unclear whether the altered connections are inherent in or secondary to the disease. Here, we sought to identify white matter tracts with altered connections and to distinguish primary or secondary alterations among 74 fiber tracts across the whole brain using an automatic tractography-based analysis method. Thirty-one chronic, 25 first-episode patients with schizophrenia and 31 healthy controls were recruited to receive diffusion spectrum magnetic resonance imaging at 3T. Seven tracts were found to exhibit significant differences between the groups; they included the right arcuate fasciculus, bilateral fornices, left superior longitudinal fasciculus I, and fibers of the corpus callosum to the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral temporal poles, and bilateral hippocampi. Post-hoc between-group analyses revealed that the connection of the callosal fibers to the bilateral DLPFC was significantly decreased in chronic patients but not in first-episode patients. In a stepwise regression analysis, the decline of the tract connection was significantly predicted by the duration of illness. In contrast, the remaining six tracts showed significant alterations in both first-episode and chronic patients and did not associate with clinical variables. In conclusion, reduced white matter connectivity of the callosal fibers to the bilateral DLPFC may be a secondary change that degrades progressively in the chronic stage, whereas alterations in the other six tracts may be inherent in the disease.
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Chen-Hao
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tzung-Jeng
authors.initials: TJ
authors.lastname: Hwang
authors.affiliation: Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yung-Chin
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: haigohwu@ntu.edu.tw.
authors.forename: Hai-Gwo
authors.initials: HG
authors.lastname: Hwu
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming H
authors.initials: MH
authors.lastname: Hsieh
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chien
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Molecular Imaging Center, National Taiwan University, Taipei, Taiwan. Electronic address: wytseng@ntu.edu.tw.
authors.forename: Wen-Yih
authors.initials: WY
authors.lastname: Isaac Tseng
mesh_terms: D000208:Acute Disease; D000328:Adult; D001921:Brain / Q000473:pathology*; D002908:Chronic Disease; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D009434:Neural Pathways / Q000473:pathology; D010363:Pattern Recognition, Automated; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012559:Schizophrenia / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
keywords: Diffusion spectrum imaging; First-episode; Schizophrenia; Tractography; White matter connectivity