Shared Genetic Risk for Epilepsy and Depression

描述(申请人提供)：抑郁症是癫痫最常见的并存状态，影响20%-55%的难治性癫痫患者和3%-9%的癫痫发作得到很好控制的患者。癫痫和情感障碍的组合在多项研究中被认为与生活质量下降、医疗保健利用率增加以及自杀想法和企图增加有关。这种共同发病的原因尚不清楚。这种共同发病可能部分归因于对慢性耻辱性疾病的心理反应。然而，另一种可能性是这两种疾病的遗传易感性相同。这项研究的主要目标是检验这一共同的遗传病因学假说。根据先前的研究，我假设情感障碍的终生患病率在家族性癫痫家系中未受影响的兄弟姐妹中高于普通人群。这些假说将通过一系列遗传流行病学研究来检验，以区分反应效应和共同的遗传易感性。我还将研究癫痫和情感障碍在临床定义的癫痫亚组中的共同发病率；特别是，我将测试在原发全面性癫痫和局灶性癫痫中情感障碍风险增加的假设。将使用可靠和有效的措施来评估情感障碍的终生患病率。查明共同的病因导致癫痫和情感障碍之间的一些共同发病率，可能有助于识别这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学家治疗癫痫患者改善对情感障碍的评估和管理提供动力。未来的研究，使用特定亚型的精确表型定义，也可以设计来定位基因。这项研究的目标与NINDS癫痫研究的“基准”是一致的：“继续识别癫痫易感基因的进展。”它还与NINDS的几个正在进行的计划公告类似：(PA编号：PA-03-169)题为“情绪的基础和翻译研究”；(PA编号：PA-02-111)题为“跨越慢性病的自我管理策略”；以及(PA编号：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."