Shared Genetic Risk for Epilepsy and Depression

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，癫痫和情感性障碍的合并与生活质量下降、医疗保健利用率增加、自杀意念和企图增加有关。这种合并症的原因尚不清楚。这种合并症的部分原因可能是由于患有慢性、耻辱性疾病的心理反应。然而，另一种可能性是对这两种疾病有共同的遗传易感性。这项研究的主要目的是验证这种共同的遗传病因假说。基于先前的研究，我假设在家族性癫痫谱系中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，以区分反应性效应和共有的遗传易感性。我还将研究癫痫和情感性障碍在临床定义的癫痫亚群中的共发病；特别是，我将检验原发性全身性癫痫和局灶性癫痫的情感性障碍风险增加的假设。将采用可靠和有效的措施来评估情感障碍的终生患病率。确定癫痫和情感性疾病共发病的共同病因可以帮助确定两种疾病的高危人群，允许早期干预，并为理解癫痫神经生物学提供一个模型。积极的结果也可能为神经科医生治疗癫痫患者时改善情感性障碍的评估和管理提供动力。未来的研究，在特定亚型中使用精炼的表型定义，也可以设计用于定位基因。本研究的目标与NINDS癫痫研究“基准”一致：“继续确定易患癫痫的基因。”它还与NINDS的几个活跃项目公告相对应：（PA编号：PA-03-169）题为“情绪的基础和转化研究”；（PA编号：PA-02-111），题为“跨越慢性病的自我管理战略”；和（PA号：PAS-03-092）题为“复杂神经和神经行为障碍的基因发现”。

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."