Neurocognitive Heterogeneity in Patients with Psychosis _ A Dimensional Approach

精神病患者的神经认知异质性_维度方法

基本信息

批准号：
8634973
负责人：
Katherine Elizabeth Burdick
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：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8634973
关键词：
Acute Address Adult Affective Affective Symptoms Alcohol or Other Drugs use Architecture Bipolar Disorder Blood specimen Brain Candidate Disease Gene Childhood Clinical Clinical Data Cluster Analysis Cognitive Cognitive deficits Comorbidity DNA DSM-IV Data Diagnosis Diagnostic Dimensions Disease Disease remission Economic Burden Environmental Risk Factor Etiology Family Functional disorder Future Genes Genetic Genome Genomics Genotype Health system Heterogeneity Impaired cognition Impairment Individual Medical Modeling Molecular Molecular Genetics Molecular Target Neurocognition Neurocognitive Occupational Outcome Pathway interactions Patient Care Patients Pattern Performance Phenotype Play Psychotic Disorders Quality of life Recording of previous events Risk Sampling Schizophrenia Sleep Structure Subgroup Symptoms System Testing Trauma Variant Veterans Work affective psychoses base clinically relevant cognitive function cohort disorder risk effective therapy endophenotype functional disability genetic risk factor genetic variant genome wide association study innovation neuropsychiatry novel prospective psychotic symptoms public health relevance risk variant social therapy development trait

项目摘要

DESCRIPTION (provided by applicant): Data from family-based, candidate gene, and genome-wide association studies converge to suggest a significant overlap in the molecular genetic risk factors for schizophrenia (SZ) and bipolar disorder (BD). This suggests that overlapping genetic variants that influence risk for these illnesses do so via effects on shared dimensional phenotypes. Among these shared traits, neurocognitive impairment, is of particular clinical relevance as it does not adequately respond to available treatments and it is among the strongest predictors of functional disability across both disorders. Moreover, there is strong evidence that neurocognitive impairment is influenced by genetic factors in both SZ and BD, making this an endophenotype which is critical toward understanding trans-disorder pathophysiology. The identification of the relevant molecular networks associated with neurocognitive functioning in psychosis is not only an important step in elucidating the causes of these disorders, but also in identifying novel treatment options for this disabling symptom domain. We will focus on neurocognition as a critical dimension that is directly associated with disease risk and attempt to identify the clinical and molecular factors that underlie cognitive impairment in psychosis. To do so, we will characterize a prospective sample of 300 patients with psychosis, including both affective and non-affective psychosis, and empirically classify subjects based on neurocognitive performance profiles. We will also collect blood samples for DNA extraction and genotype a targeted list of high priority SNPs (based on prior association with BD/SZ risk and/or neurocognitive functioning) using a customized array. These data will be applied to a multidimensional modeling analyses in an effort to identify the risk alleles and molecular pathways that contribute to neurocognitive impairment in psychosis.

描述（由申请人提供）：来自基于家族的候选基因和全基因组关联研究的数据表明，精神分裂症 (SZ) 和双相情感障碍 (BD) 的分子遗传风险因素存在显着重叠。这表明影响这些疾病风险的重叠遗传变异是通过对共享维度表型的影响来实现的。在这些共同特征中，神经认知障碍具有特殊的临床相关性，因为它对现有的治疗没有充分的反应，并且它是这两种疾病功能障碍的最强预测因素之一。此外，有强有力的证据表明，SZ 和 BD 的神经认知障碍均受到遗传因素的影响，这使其成为对于理解跨疾病病理生理学至关重要的内表型。鉴定与精神病神经认知功能相关的相关分子网络不仅是阐明这些疾病原因的重要一步，而且也是确定针对这种致残症状领域的新治疗方案的重要一步。我们将重点关注神经认知作为与疾病风险直接相关的关键维度，并尝试确定精神病认知障碍背后的临床和分子因素。为此，我们将描述 300 名精神病患者的前瞻性样本，包括情感性和非情感性精神病，并根据神经认知表现特征对受试者进行经验分类。我们还将收集血液样本进行 DNA 提取，并使用定制阵列对高优先级 SNP 的目标列表进行基因分型（基于先前与 BD/SZ 风险和/或神经认知功能的关联）。这些数据将应用于多维建模分析，以确定导致精神病神经认知障碍的风险等位基因和分子途径。