权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

White Matter Abnormalities in the Schizophrenia Spectrum

精神分裂症谱系中的白质异常

基本信息

批准号：
8246551
负责人：
Larry J Siever
金额：
--
依托单位：
JAMES J PETERS VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8246551
关键词：
Accounting Affective Alleles Anisotropy Anterior Antipsychotic Agents Brain Brain region Brodmann&apos s area Caring Characteristics Chronic Chronic Schizophrenia Clinical Cognitive Communication DNA Data Development Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Dimensions Disease Environment Fiber Forcep Functional disorder Genes Genetic Genetic Predisposition to Disease Genetic Variation Genomics Goals Gray unit of radiation dose Health Care Costs Impaired cognition Individual Inferior Institutionalization Internal Capsule Intervention Lead Limb structure Magnetic Resonance Imaging Maps Measurable Measures Mediating Minor Modeling Molecular Abnormality Morphologic artifacts Myelin Neuregulin 1 Neuregulins Neuromodulator Occupational Oligodendroglia Pathologic Pathology Patients Pharmaceutical Preparations Phenotype Population Psychophysiology Psychotic Disorders Research Risk Sampling Schizophrenia Schizotypal Personality Disorder Series Severity of illness Susceptibility Gene Symptoms Temporal Lobe Translations Variant base cingulate cortex cognitive function frontal lobe functional disability genetic association gray matter interest myelination perceptual organization pre-clinical trait white matter

项目摘要

DESCRIPTION (provided by applicant): Project Summary In order to identify promising new targets for intervention in schizophrenia, a better understanding of its pathologic circuitry and underlying genetic susceptibilities is required. A promising pathophysiologic model of schizophrenia is the white matter hypothesis which posits oligodendrocyte abnormalities resulting in defective myelination and ultimately disordered white matter tracts impair effective communication between brain regions contributing to the cognitive, affective, perceptual, and interpersonal deficits/disorganization characteristics of schizophrenia. A number of susceptibility genes are implicated in white abnormalities and schizophrenia including neuregulin 1 (NRG1) and ERBB4. In this series of studies, we propose to investigative a model of white matter disorganization in schizophrenia driven by genetic susceptibilities in NRG1 and ERBB4 as well as other white matter related genes in interaction with adverse environments during brain development in which white matter disorder would partially mediate the genetic effects on the schizophrenic phenotype and particularly its deficit and disorganization symptoms. We have selected schizotypal personality disorder (SPD) subjects as our choice of phenotype as they represent a form of schizophrenia without the confounding artifacts of chronic neuroleptic treatment, long term psychosis, and even institutionalization, and offers an opportunity to parse the underlying dimensions of schizophrenia. The proposed studies aim to evaluate white matter organization through fractional anisotropy (FA) as evaluated by diffusion tensor imaging (DTI) and grey and white matter volumes in the schizophrenia spectrum by structural MRI and their relationship to allelic variation in two underlying susceptibility genes NRG1 and ERBB4. It is hypothesized that reduced FA in temporal and frontal white matter tracts is association with SPD, the prototypic schizophrenia spectrum disorder minimizing the confounding artifacts associated with chronic schizophrenia, as well as the deficit and disorganization symptom dimensions of SPD. Both reduced FA and SPD are hypothesized to be associated with alleles in NRG1 and ERBB4. It is also hypothesized that reduced gray matter volume in temporal lobe is associated with SPD. Exploratory path analysis will evaluate to what extent the association of alleles of NRG1 and ERBB4 with SPD are mediated through white matter abnormalities. Other analyses will explore the relationship of regions of interest to these genes' alleles, the possible association of these genetic alleles with temporal grey matter volume, and the relationship of FA and associated genetic alleles to the deficit and disorganization symptoms of SPD.

描述（由申请人提供）：