Shared Genetic Risk for Epilepsy and Depression

癫痫和抑郁症的共同遗传风险

• 批准号: 7871319
• 负责人: Gary A. Heiman
• 金额: $ 15.33万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7871319
• 关键词: Accounting; Affect; Benchmarking; Chronic; Chronic Disease; Comorbidity; Complex; Cryptogenic Epilepsies; Data; Disease; Early treatment; Emotions; Epidemiologic Studies; Epilepsy; Etiology; Evaluation; Family; Family member; Feeling suicidal; Future; General Population; Generalized Epilepsy; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Goals; Individual; Interview; LGI1 gene; Measures; Mental Depression; Modeling; Mood Disorders; Mutation; NIH Program Announcements; National Institute of Neurological Disorders and Stroke; Neurobiology; Neurologic; Neurologist; Partial Epilepsies; Patients; Phenotype; Prevalence; Quality of life; Reaction; Refractory; Research; Risk; Seizures; Self Management; Series; Siblings; Subgroup; Susceptibility Gene; Syndrome; Testing; Translational Research; base; design; gene discovery; genetic pedigree; health care service utilization; high risk; improved; neurobehavioral disorder; psychologic

DESCRIPTION (provided by applicant): Depression is the most common co-morbid condition in epilepsy, affecting between 20-55% of patients with refractory epilepsy and 3-9% of patients with well-controlled seizures. The combination of epilepsy and affective disorders has been associated in multiple studies with diminished quality of life, increased healthcare utilization, and increased suicidal ideation and attempts. The cause of this co-morbidity is unknown. This co-morbidity may be due, in part, to a psychological reaction to having a chronic, stigmatizing disorder. However, another possibility is a shared genetic susceptibility to both disorders. The broad goal of this study is to test this shared genetic etiology hypothesis. Based on prior research, I hypothesize that the lifetime prevalence of affective disorders is higher in unaffected siblings from familial epilepsy pedigrees than in the general population. The hypotheses will be tested through a series of genetic epidemiological studies to distinguish between reactive effects and shared genetic susceptibility. I will also examine the co- morbidity of epilepsy and affective disorders within clinically defined subgroups of epilepsy; in particular, I will test the hypothesis that risk of affective disorders is increased in primary generalized epilepsy, as well as in focal epilepsy. Reliable and valid measures will be used to assess a lifetime prevalence of affective disorders. Identifying that shared etiology accounts for some of the co-morbidity between epilepsy and affective disorders could help identify individuals at high-risk for both disorders, allow for early intervention, and provide a model for understanding epilepsy neurobiology. Positive results may also provide an impetus for improved assessment and management of affective disorders by neurologists treating people with epilepsy. Future studies, using the refined phenotype definitions in the specific subtypes, could also be designed to locate genes. The goal of this study is consistent with the NINDS "Benchmarks" for Epilepsy Research: "Continue the progress of identifying the genes predisposing to epilepsy." It also parallels several active Program Announcements from NINDS: (PA Number: PA-03-169) entitled "Basic and Translational Research in Emotion"; (PA Number: PA-02-111) entitled "Self-Management Strategies Across Chronic Diseases"; and (PA Number: PAS-03-092) entitled "Gene Discovery For Complex Neurological And Neurobehavioral Disorders."

描述（由申请人提供）：抑郁症是癫痫最常见的合并症，影响 20-55% 的难治性癫痫患者和 3-9% 癫痫控制良好的患者。多项研究表明，癫痫和情感障碍的结合与生活质量下降、医疗保健利用率增加以及自杀意念和尝试增加有关。这种共病的原因尚不清楚。这种共病可能部分是由于患有慢性污名化疾病而产生的心理反应。然而，另一种可能性是对这两种疾病具有共同的遗传易感性。这项研究的主要目标是检验这一共同的遗传病因学假设。根据先前的研究，我假设来自家族性癫痫谱系的未受影响的兄弟姐妹中情感障碍的终生患病率高于一般人群。这些假设将通过一系列遗传流行病学研究进行检验，以区分反应效应和共同的遗传易感性。我还将检查临床定义的癫痫亚组中癫痫和情感障碍的共病；特别是，我将检验原发性全身性癫痫和局灶性癫痫中情感障碍风险增加的假设。将使用可靠且有效的措施来评估情感障碍的终生患病率。确定癫痫和情感障碍之间的一些共病的共同病因可以帮助识别这两种疾病的高危个体，允许早期干预，并为理解癫痫神经生物学提供模型。积极的结果还可能为治疗癫痫患者的神经科医生改进情感障碍的评估和管理提供动力。未来的研究，使用特定亚型中的精细表型定义，也可以设计来定位基因。这项研究的目标与 NINDS 癫痫研究“基准”一致：“继续鉴定诱发癫痫的基因。”它还与 NINDS 的几个活跃计划公告并行：（PA 编号：PA-03-169）题为“情感的基础和转化研究”； （PA 编号：PA-02-111）题为“慢性病的自我管理策略”； （PA 编号：PAS-03-092）标题为“复杂神经学和神经行为疾病的基因发现”。