Heredity and functional association of the right arcuate fasciculus in schizophrenia
Date Issued
2015
Date
2015
Author(s)
Wu, Chen-Hao
Abstract
Trait markers aid in the separation of heterogeneous phenotypes into distinct subtypes and provide more efficient routes for the discovery of the genetic underpinnings of disease. Recent diffusion magnetic resonance imaging (MRI) research has proposed that the microstructural integrity of white matter is a trait marker for schizophrenia. Although tractography-based analysis is a better approach for measuring the microstructural integrity of white matter, manual tractography is operator-dependent and extremely time-consuming if a large number of tracts are to be analyzed. In this study, we sought to identify the trait markers of schizophrenia using a novel, automatic tractography-based analysis method. We analyzed tract integrities in a cohort of schizophrenic patients, unaffected siblings and healthy controls. We found that the white matter integrity of the right arcuate fasciculus was significantly impaired in both unaffected siblings and schizophrenic patients in a predictable, graded pattern. Our results suggest that the right arcuate fasciculus is a candidate trait marker and could be valuable for establishing links between genetic liabilities and specific clinical phenotypes. Although the right arcuate fasciculus was identified as a candidate trait marker of schizophrenia, it is unclear how the structure and function of the white matter tract is altered, how these alterations are related to each other, and how these alterations are associated with psychotic symptoms. To address these questions, we conducted a study combining diffusion MRI and functional MRI to identify the relationships between structure and function in the right arcuate fasciculus. A positive correlation was found between the microstructural integrity of the right arcuate fasciculus and the corresponding functional lateralization. When correlated with clinical symptoms, both the microstructural integrity of the right arcuate fasciculus and the corresponding functional lateralization were negatively correlated with the delusion/hallucination dimension scores. Our results suggest that the impaired structural integrity of the right arcuate fasciculus is related to a reduction in the corresponding functional lateralization and that these alterations might aggravate auditory verbal hallucinations in schizophrenia. In summary, these results demonstrate the hereditary traits of the right arcuate fasciculus and reveal its complex structure-function relationships in relation to specific clinical phenotypes, suggesting that the right arcuate fasciculus is a trait marker that could be useful in screening for schizophrenia-related genes and in the early diagnosis of schizophrenia.
Subjects
schizophrenia
endophenotype
trait marker
diffusion spectrum imaging
tractography
functional MRI
Type
thesis
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