Shared Genetic Risk for Epilepsy and Depression

描述（由申请人提供）：抑郁是癫痫中最常见的共病，影响20-55%的难治性癫痫患者和3-9%的癫痫发作控制良好的患者。在多项研究中，癫痫和情感障碍的组合与生活质量降低、医疗保健利用增加以及自杀意念和企图增加相关。这种合并症的原因尚不清楚。这种并发症可能部分是由于对患有慢性耻辱性疾病的心理反应。然而，另一种可能性是两种疾病的遗传易感性相同。这项研究的主要目的是检验这种共同的遗传病因假说。基于先前的研究，我假设情感性精神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一般人群。将通过一系列遗传流行病学研究来检验这些假设，以区分反应性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率;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。将使用可靠有效的措施来评估情感性精神障碍的终生患病率。确定癫痫和情感障碍之间的共同病因可以帮助识别两种疾病的高风险个体，允许早期干预，并为理解癫痫神经生物学提供模型。积极的结果也可能为改善神经科医生治疗癫痫患者的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，也可以设计定位基因。这项研究的目标与NINDS癫痫研究的“基准”一致：“继续识别癫痫易感基因的进展。它还与NINDS的几个活动计划公告平行：（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“慢性疾病的自我管理策略”;和（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."