Activity as an endophenotype for genetic studies

描述(由申请人提供)：NIMH研究领域标准(RDoC)项目通过定义跨越障碍的功能的基本维度，为基础研究和翻译研究的整合提供了一个框架。在几种高度丧失能力和衰弱的精神障碍中观察到的昼夜节律和睡眠障碍，代表了觉醒和调节系统RDoC领域的关键结构。在精神病人群中研究昼夜节律和睡眠障碍是困难的，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活动成像技术应用于大规模基因研究的可行性。 跨传统诊断类别。为了促进这些研究，我们需要评估大规模、纵向活动模式的新方法。我们的目标是：1.识别活动描记设备，并建立适用于同时和纵向确定活动和睡眠的方案：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；以及目标2.测试使用活动描记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度。在情绪诊所出现的受试者和一组双胞胎代表中，与情绪、睡眠：清醒或休息：活动模式相关的参数的个体差异测量和遗传率的比较，将为跨几种疾病的大规模遗传学研究的参数选择提供重要的初步见解。最后，RDoC倡议是新的，将需要整合各领域的方法。这项提议将为跨学科团队(遗传学家、临床心理学家、精神病学家和统计学家)提供机会，启动与睡眠和昼夜节律紊乱有关的基于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.