Neural and Behavioral Mechanisms of Angry Hostility in Depression

摘要 尽管几十年来已经有了多种不同的抑郁症治疗方法，但全球 疾病负担一直在稳步增长。抑郁症现在是全世界导致残疾的主要原因之一。 目前抑郁症的治疗策略基本上仍是反复试验，只有不到40%的患者 对给定的治疗做出反应，并将这种反应维持一年，即使治疗仍在继续。一个中环 改善这些结果的障碍是需要确定更好的抑郁症表型的特征，这些表型 与当前的症状星座和可修改的神经生物学靶点更紧密地结合 诊断代码。我们小组和其他人的研究结果表明，其中一个这样的表型涉及 在经历负面经历后，容易经历愤怒、敌意和易怒，并在 咄咄逼人的、过于敌视的态度(以下称为愤怒的敌意)。我们的初步数据表明 愤怒的敌意表型与神经区域功能改变的特定模式有关 支持情绪处理和情绪调节。此外，愤怒的敌意似乎很强烈 与挑衅后的敌对、攻击性行为有关，与现实世界的人际关系和工作有关- 会加重抑郁症状的功能障碍。这个项目的主要目标是测试一个 成年抑郁症患者中愤怒敌意水平较高的新模型 神经功能和行为异常的特定模式，导致不良的功能结果和未来 症状。为了实现这些目标，150名至少有轻微抑郁症状的成年人(18-45岁)将 将被招募，以及100名人口统计匹配、精神健康的个人。参赛者将完成 临床、神经成像和实验室行为评估，以及4、8和12个月的随访 评估和四个为期10天的生态瞬时评估方案。该项目将检查1)是否 愤怒敌意与情绪处理和情绪调节的神经功能异常有关 地区；2)愤怒的敌意是否与实验室和现实世界中的攻击行为有关 3)先验神经系统和行为异常是否预示着较差的实际生活质量。 世界功能和精神症状在12个月的随访中。该项目的目标与 国家精神卫生研究所的战略目标。此外，这项研究的结果具有潜在的 描述愤怒情绪高涨的神经生物学基础、行为机制和现实后果 成年抑郁症患者的敌意。未来的工作将致力于开发个性化的治疗方法，以针对 这项研究确定了神经机制，以减轻症状和改善功能预后 患有抑郁症的成年人有更高水平的愤怒敌意。

ABSTRACT Despite the fact that multiple different treatments for depression have been available for decades, the global burden of the illness has grown steadily. Depression is now one of the leading causes of disability worldwide. Current treatment strategies for depression remain largely trial-and-error, and fewer than 40% of patients respond to a given treatment and sustain that response for a year, even when treatment is continued. A central barrier to improving these outcomes is the need to characterize better phenotypes of depressive illness that are more closely aligned to modifiable neurobiological targets than are current symptom constellations and diagnostic codes. Findings from our group, and from others, suggest that one such phenotype involves the propensity to experience anger, hostility, and irritability following negative experiences and to respond in an aggressive, overly hostile manner (hereafter denoted Angry Hostility). Our preliminary data suggest that the Angry Hostility phenotype is associated with a particular pattern of altered functioning in neural regions that support emotion processing and emotion regulation. Furthermore, Angry Hostility appears to be strongly associated with hostile, aggressive behaviors following provocation and with real-world interpersonal and work- functioning impairments that can exacerbate depressive symptoms. The primary goal of this project is to test a novel model through which higher levels of Angry Hostility among adults with depression are associated with specific patterns of abnormal neural function and behavior, leading to poor functional outcomes and future symptoms. To achieve these goals, 150 adults (18-45 years old) with at least mild symptoms of depression will be recruited, as will 100 demographically matched, psychiatrically healthy individuals. Participants will complete clinical, neuroimaging, and laboratory behavioral assessments, as well as 4-, 8-, and 12-month follow-up assessments and four 10-day ecological momentary assessment protocols. The project will examine 1) whether Angry Hostility is associated with abnormal neural function in emotion processing and emotion regulation regions; 2) whether Angry Hostility is associated with aggressive behaviors in the laboratory and in real-world settings; and 3) whether abnormalities in a-priori neural systems and behaviors prospectively predict poorer real- world functioning and psychiatric symptoms over the 12-month follow-up. The aims of the project match well with the strategic goals of the National Institute of Mental Health. Moreover, the results of this study have the potential to describe the neurobiological bases, behavioral mechanisms, and real-world consequences of elevated Angry Hostility among adults with depression. Future work will aim to develop personalized treatments to target the neural mechanisms identified in this study in order to reduce symptoms and improve functional outcomes for adults with depression who have higher levels of Angry Hostility.