Family Study of Reward and Threat Sensitivity in Internalizing Psychopathology

描述（由申请人提供）：本研究的目的是检查两个transdiagnosis维度-降低的奖励预期（RRA）和对潜在威胁的高度敏感性（SPT）-是否代表内化的风险因素（即，抑郁和焦虑）精神病理学。拟议的项目是重要的，因为内化的精神病理学是非常异质性的，提出了关于分类诊断命名法的有效性的问题（例如，DSM-IV）。因此，本研究采取研究领域标准（RDoC）的方法，并试图确定潜在的维度结构，跨越传统的精神病理学类别。然而，拟议的项目通过检查拟议的维度结构是否反映1）精神病理学的风险标志物（通过经典的家庭研究方法定义风险）和2）可分离的结构（即，RDoC结构的判别有效性）。具体来说，我们假设RRA（而不是SPT）将预测抑郁症的风险，而SPT（而不是RRA）将预测某些焦虑症状的风险（例如，恐慌）。我们将从社区招募210名具有广泛内化精神病理学的先证者，并使用多种生理，行为和自我报告措施评估RRA和SPT。我们的RRA和SPT的主要指标将分别是预期奖励时的EEG α不对称性和预期潜在威胁时的惊吓反应。这些心理生理学变量已被广泛用于衡量RRA和SPT和挖掘预期的情感状态，从而锐化我们的判别效度测试。此外，惊吓任务评估了对急性威胁和潜在威胁的敏感性，因此允许从第三个RDoC结构（急性威胁）测试RRA和SPT的判别效度。 该研究旨在审查：1）RRA和SPT是否可预测家族史（通过一级亲属的直接访谈进行评估）内化精神病理学的可分离方面; 2）RRA和SPT指标在“健康”人群中是否异常（或低症状）先证者的年龄匹配的兄弟姐妹具有高水平的内化症状; 3）RRA和SPT的家族聚集性;（4）使用RRA和SPT的心血管、行为和自我报告指标对我们的RRA和SPT电生理测量进行结构效度分析。这项研究的影响将是在确定重要的潜在机制，发挥作用的内在精神病理学的病因。此外，如果这些指标被证明是精神病理学风险的家族标志物，它们将成为预防/早期干预工作的优秀（且相对便宜）实验室目标以及治疗开发研究的目标。 公共卫生相关性：拟议的项目采取了一种新的方法来确定内在精神病理学的风险因素（即，抑郁和/或焦虑），通过检查特定潜在维度的变化是否意味着这些使人衰弱和代价高昂的病症的风险。具体来说，这项研究将研究是否降低对奖励的敏感性和提高对威胁的敏感性代表抑郁症和某些类型的焦虑症状的风险的可分离维度。

DESCRIPTION (provided by applicant): The purpose of this study is to examine whether two transdiagnostic dimensions - reduced reward anticipation (RRA) and heightened sensitivity to potential threat (SPT) - represent risk factors for internalizing (i.e., depression and anxiety) psychopathology. The proposed project is significant because internalizing psychopathologies are very heterogeneous, raising questions as to the validity of the categorical diagnostic nomenclature (e.g., DSM-IV). This study therefore takes the Research Domain Criteria (RDoC) approach and seeks to identify underlying dimensional constructs that cut across traditional categories of psychopathology. However, the proposed project extends the aims of RDoC by examining whether the proposed dimensional constructs reflect 1) risk markers for psychopathology (defining risk via the classic family study method) and 2) separable constructs (i.e., the discriminant validity of RDoC constructs). Specifically, we hypothesize that RRA (but not SPT) will predict risk for depressive symptomatology and SPT (but not RRA) will predict risk for certain anxiety symptoms (e.g., panic). We will recruit 210 probands with a wide range of internalizing psychopathology from the community and assess RRA and SPT using multiple physiological, behavioral, and self-report measures. Our primary indicators of RRA and SPT will be EEG alpha asymmetry while anticipating reward and startle response while anticipating a potential threat, respectively. These psychophysiological variables have been used extensively as measures of RRA and SPT and both tap anticipatory affective states, thus sharpening our test of discriminant validity. In addition, the startle task assesses sensitivity to acute threat a well as potential threat and therefore allows a test of the discriminant validity of RRA and SPT from this third RDoC construct (acute threat). The study aims to examine: 1) whether RRA and SPT predict family history (assessed via direct interview of 1st degree relatives) of separable facets of internalizing psychopathology; 2) whether indicators of RRA and SPT are abnormal in 'healthy' (or low symptom) age-matched siblings of probands with high levels of internalizing symptoms; 3) the familial aggregation of RRA and SPT; and 4) the construct validity of our electrophysiological measures of RRA and SPT using cardiovascular, behavioral, and self- report indicators of these two constructs. The impact of the study would be in identifying important underlying mechanisms that play a role in the etiopathogeneses of internalizing psychopathology. In addition, if these indicators prove to be familial markers of risk for psychopathology, they would make excellent (and relatively inexpensive) laboratory targets for prevention/early intervention efforts as well as targets for treatment development studies. PUBLIC HEALTH RELEVANCE: The proposed project takes a novel approach to identifying risk factors for internalizing psychopathology (i.e., depression and/or anxiety) by examining whether variation on particular underlying dimensions connote risk for these debilitating and costly conditions. Specifically, this study will examine whether a reduced sensitivity to reward and a heightened sensitivity to threat represent separable dimensions of risk for depression and certain types of anxiety symptoms.