Family Study of Reward and Threat Sensitivity in Internalizing Psychopathology

描述(由申请人提供)：这项研究的目的是检查两个跨诊断维度-减少的奖励预期(RRA)和对潜在威胁的高度敏感(SPT)-是否代表内在化(即抑郁和焦虑)精神病理学的风险因素。拟议的项目意义重大，因为内化精神病理学是非常不同的，对分类诊断命名法(例如，DSM-IV)的有效性提出了质疑。因此，本研究采用研究领域标准(RDoC)的方法，试图确定跨越精神病理学传统类别的潜在维度结构。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记物(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结构的区分效度)来扩展RDoC的目标。具体地说，我们假设RRA(而不是SPT)将预测抑郁症状的风险，而SPT(但不是RRA)将预测某些焦虑症状(例如，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学的先证者，并使用多种生理、行为和自我报告测量来评估RRA和SPT。我们对RRA和SPT的主要指标将是脑电阿尔法不对称性，同时分别预测奖励和惊吓反应，同时预测潜在威胁。这些心理生理学变量被广泛用作RRA和SPT的测量，两者都利用预期的情感状态，从而加强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度，因此可以从第三个RDoC结构(急性威胁)来测试RRA和SPT的判别效度。这项研究的目的是检验：1)RRA和SPT是否可以预测内化精神病理学可分离方面的家族史(通过直接采访进行评估)；2)RRA和SPT的指标在具有高水平内化症状的先证者的年龄匹配的健康(或低症状)兄弟姐妹中是否异常；3)RRA和SPT的家族聚集性；以及4)我们使用这两个结构的心血管、行为和自我报告指标对RRA和SPT的电生理学测量的结构效度。这项研究的影响将是确定重要的潜在机制，这些机制在内化精神病理学的病因中发挥作用。此外，如果这些指标被证明是精神病的家族性风险标志，它们将成为预防/早期干预努力的优秀(和相对廉价的)实验室目标，以及治疗发展研究的目标。 公共卫生相关性：拟议的项目采用了一种新的方法来确定内在化精神病理学(即抑郁和/或焦虑)的风险因素，方法是检查特定潜在维度的变化是否意味着这些虚弱和代价高昂的疾病的风险。具体地说，这项研究将检查对奖励的敏感度降低和对威胁的敏感度增强是否代表抑郁风险和某些类型的焦虑症状的可分离维度。

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.