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Large-scale white matter network reorganization in posttraumatic stress disorder.

ABSTRACT: Recently, graph theoretical approaches applied to neuroimaging data have advanced understanding of the human brain connectome and its abnormalities in psychiatric disorders. However, little is known about the topological organization of brain white matter networks in posttraumatic stress disorder (PTSD). Seventy-six patients with PTSD and 76 age, gender, and years of education-matched trauma-exposed controls were studied after the 2008 Sichuan earthquake using diffusion tensor imaging and graph theoretical approaches. Topological properties of brain networks including global and nodal measurements and modularity were analyzed. At the global level, patients showed lower clustering coefficient (p = .016) and normalized characteristic path length (p = .035) compared with controls. At the nodal level, increased nodal centralities in left middle frontal gyrus, superior and inferior temporal gyrus and right inferior occipital gyrus were observed (p?

SUBMITTER: Suo X

PROVIDER: S-EPMC6865776 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Large-scale white matter network reorganization in posttraumatic stress disorder.

Suo Xueling X Lei Du D Li Wenbin W Chen Fuqin F Niu Running R Kuang Weihong W Huang Xiaoqi X Lui Su S Li Lingjiang L Sweeney John A JA Gong Qiyong Q

Human brain mapping 20190731 16

Recently, graph theoretical approaches applied to neuroimaging data have advanced understanding of the human brain connectome and its abnormalities in psychiatric disorders. However, little is known about the topological organization of brain white matter networks in posttraumatic stress disorder (PTSD). Seventy-six patients with PTSD and 76 age, gender, and years of education-matched trauma-exposed controls were studied after the 2008 Sichuan earthquake using diffusion tensor imaging and graph ...[more]

PMID: 31365184

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Project description:Genetic susceptibility factors behind psychiatric disorders typically contribute small effects individually. A possible explanation for the missing heritability is that the effects of common variants are not only polygenic but also non-additive, appearing only when interactions within large groups are taken into account. Here, we tested this hypothesis for schizophrenia (SZ) and bipolar disorder (BP) disease risks, and identified genetic factors shared with posttraumatic stress disorder (PTSD). When considered independently, few single-nucleotide polymorphisms (SNPs) reached genome-wide significance. In contrast, when SNPs were selected in groups (containing up to thousands each) and the collective effects of all interactions were estimated, the association strength for SZ/BP rose dramatically with a combined sample size of 7187 cases and 8309 controls. We identified a large number of genes and pathways whose association was significant only when interaction effects were included. The gene with highest association was CSMD1, which encodes a negative regulator of complement activation. Pathways for glycosaminoglycan (GAG) synthesis exhibited strong association in multiple contexts. Taken together, highly associated pathways suggested a pathogenesis mechanism where maternal immune activation causes disruption of neurogenesis (compounded by impaired cell cycle, DNA repair and neuronal migration) and deficits in cortical interneurons, leading to symptoms triggered by synaptic pruning. Increased risks arise from GAG deficiencies causing complement activation and excessive microglial action. Analysis of PTSD data sets suggested an etiology common to SZ/BP: interneuron deficiency can also lead to impaired control of fear responses triggered by trauma. We additionally found PTSD risk factors affecting synaptic plasticity and fatty acid signaling, consistent with the fear extinction model. Our results suggest that much of the missing heritability of psychiatric disorders resides in non-additive interaction effects.

Dataset Information

Large-scale white matter network reorganization in posttraumatic stress disorder.

Publications

Large-scale white matter network reorganization in posttraumatic stress disorder.

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