Activity as an endophenotype for genetic studies

描述（由申请人提供）：NIMH研究领域标准（RDoC）项目通过定义跨疾病的功能的基本维度，为基础和转化研究的整合提供了一个框架。在几种高度失能和衰弱的精神障碍中观察到的昼夜节律和睡眠障碍代表了唤醒和调节系统RDoC域中的关键结构。精神病人群的昼夜节律和睡眠障碍的研究是困难的，许多小规模研究之间的矛盾结果可能是由于高度的遗传和表型异质性。我们的长期目标是评估将腕动计应用于大规模遗传学研究的可行性 在传统的诊断类别中。为了促进这些研究，我们需要评估新的方法，大规模的，纵向剖析的活动模式。我们的目标是：目标1。识别体动仪设备，并建立适用于同时和纵向确定活动和睡眠的协议：从门诊情绪障碍治疗计划招募的100名受试者的觉醒模式和情绪症状;目标2。在来自宾夕法尼亚州双胞胎登记处的一组250对双胞胎中，测试使用体动记录设备收集的一系列定量参数（包括活动水平、活动和休息开始的时间、幅度、活动-休息周期的组织）和自我报告的情绪症状的遗传性。个体差异的措施和遗传性的参数相关的情绪，睡眠：清醒或休息：活动模式的受试者在情绪诊所和一组双胞胎代表的比较将提供重要的初步见解参数选择的大规模遗传研究在几种疾病。最后，RDOC倡议是新的，将需要整合跨领域的方法。该提案将为跨学科团队（遗传学家，临床心理学家，精神病学家和统计学家）提供一个机会，以启动与睡眠和昼夜节律紊乱相关的基于RDoC的表型。

DESCRIPTION (provided by applicant): The NIMH Research Domain Criteria (RDoC) Project provides a framework for the integration of basic and translational research, by defining basic dimensions of function that cut across disorders. Circadian and sleep disturbances, observed in several highly incapacitating and debilitating mental disorders, represent the key constructs within the Arousal and Regulatory system RDoC Domain. The study of circadian and sleep disturbances in psychiatric populations is difficult and contradictory results between numerous small scale studies may be due to a high degree of genetic and phenotypic heterogeneity. Our long-term aim is to evaluate the feasibility of applying actigraphy for large-scale genetic studies across traditional diagnostic categories. To facilitate these studies, we need to evaluate novel methods for large scale, longitudinal profiling of activity patterns. Our Aims are: Aim 1. To identify actigraphy devices and establish protocols suitable for concurrent and longitudinal ascertainment of activity and sleep: wake patterns and mood symptoms in 100 subjects recruited from an outpatient mood disorders treatment program; and Aim 2. To test heritability of an array of quantitative parameters collected using actigraphy devices (including activity levels, timing of activity and rest onsets, amplitude, organization of activity-rest cycles) and self- reported mood symptoms in a set of 250 twin pairs from the Pennsylvania Twin Registry. The comparison of individual difference measures and heritability of parameters related to mood, sleep: wake or rest: activity patterns in subjects presenting at the mood clinic and in a set of twins represents will provide important preliminary insights into parameter selection for large scale genetic studies across several disorders. Finally, the RDoC initiative is new and will require an integration of approaches across fields. This proposal will provide an opportunity for the interdisciplinary team (geneticists, clinical psychologists, psychiatrists and statisticians) t initiate RDoC-based phenotyping relevant to sleep and circadian disturbances.