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跨诊断维度-奖励预期降低（RRA）和对潜在威胁的敏感性提高(SPT) -是否代表内化（即抑郁和焦虑）精神病理学的风险因素。拟议的项目是重要的，因为内化精神病理学是非常异构的，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，本研究采用研究领域标准（RDoC）方法，并试图确定跨越传统精神病理学类别的潜在维度结构。然而，该项目扩展了RDoC的目的，通过检验提出的维度构念是否反映了1)精神病理学的风险标记（通过经典的家庭研究方法定义风险）和2)可分离构念（即RDoC构念的区别效度）。具体来说，我们假设RRA（而不是SPT）会预测抑郁症状的风险，而SPT（而不是RRA）会预测某些焦虑症状（如恐慌）的风险。我们将从社区招募210名具有广泛内化精神病理的先证者，并使用多种生理、行为和自我报告测量来评估RRA和SPT。RRA和SPT的主要指标分别是预期奖励时的脑电图α不对称和预期潜在威胁时的惊吓反应。这些心理生理变量已被广泛用于RRA和SPT的测量，两者都涉及预期情感状态，从而提高了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）中测试RRA和SPT的区别效度。本研究旨在探讨：1)RRA和SPT是否能预测内化精神病理可分方面的家族史（通过直接访谈一级亲属评估）；2)内化症状高水平先证者的“健康”（或低症状）年龄匹配兄弟姐妹的RRA和SPT指标是否异常；3) RRA和SPT的家族聚集性；4)使用心血管、行为和自我报告指标对RRA和SPT进行电生理测量的构念效度。这项研究的影响在于确定在内化精神病理学发病机制中起作用的重要潜在机制。此外，如果这些指标被证明是精神病理学风险的家族性标记，它们将成为预防/早期干预工作以及治疗开发研究的优秀（且相对便宜）实验室目标。

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.