Neural and Behavioral Mechanisms of Angry Hostility in Depression

摘要 尽管抑郁症的多种不同治疗方法已经存在了几十年， 疾病的负担不断增加。抑郁症现在是全球残疾的主要原因之一。 目前抑郁症的治疗策略在很大程度上仍然是试错法，只有不到40%的患者 对特定的治疗有反应，并保持这种反应一年，即使继续治疗。中央 改善这些结果的障碍是需要更好地表征抑郁症的表型， 与当前症状星座相比，与可修改的神经生物学目标更紧密地对齐， 诊断代码我们小组和其他人的研究结果表明，其中一种表型涉及 在经历负面经历后，倾向于经历愤怒、敌意和易怒，并以一种 咄咄逼人，过于敌对的态度（下文称为愤怒的敌意）。我们的初步数据表明， 愤怒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，愤怒的敌意似乎强烈 与挑衅后的敌对、攻击行为以及现实世界中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 一种新的模型，通过该模型，成年抑郁症患者的愤怒敌意水平较高， 异常的神经功能和行为的特定模式，导致不良的功能结果和未来 症状为了实现这些目标，150名至少有轻度抑郁症状的成年人（18-45岁）将 招募100名人口统计学上匹配的精神健康个体。参与者将完成 临床、神经影像学和实验室行为评估，以及4、8和12个月随访 评估和四个为期10天的生态瞬时评估协议。该项目将审查1）是否 愤怒敌意与情绪加工和情绪调节的神经功能异常有关 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 设置;以及3）先验神经系统和行为的异常是否前瞻性地预测较差的真实的- 12个月随访期间的世界功能和精神症状。该项目的目标与 国家心理健康研究所的战略目标。此外，这项研究的结果有可能 描述神经生物学基础、行为机制和愤怒情绪升高的现实后果。 成人抑郁症患者的敌意。未来的工作将旨在开发个性化的治疗方法，以针对 本研究中确定的神经机制，以减少症状和改善功能结果， 患有抑郁症的成年人，他们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.