Neural and Behavioral Mechanisms of Angry Hostility in Depression

抑郁症中愤怒敌意的神经和行为机制

• 批准号: 10744840
• 负责人: Jay C Fournier
• 金额: $ 81.61万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744840
• 关键词: Adult; Age; Aggressive behavior; Amygdaloid structure; Anger; Area; Attention; Behavior; Behavior assessment; Behavioral; Behavioral Mechanisms; Clinical; Clinical assessments; Code; Data; Depressed mood; Detection; Development; Diagnostic; Dimensions; Ecological momentary assessment; Elements; Emotional; Emotions; Evaluation; Face; Feedback; Fusiform gyrus; Future; Goals; Hostility; Impairment; Individual; Inferior frontal gyrus; Insula of Reil; Laboratories; Lead; Life; Link; Measures; Mediating; Mental Depression; Middle frontal gyrus structure; Modeling; Motor; National Institute of Mental Health; Neural Pathways; Neurobiology; Neuronal Dysfunction; Neurophysiology - biologic function; Outcome; Participant; Patients; Pattern; Phenotype; Prefrontal Cortex; Process; Protocols documentation; Quality of life; Recording of previous events; Regulation; Risk; Sensory; Severities; Short-Term Memory; Standardization; Support System; Symptoms; System; Testing; Visual; Work; base; brain dysfunction; burden of illness; depressive symptoms; disability; emotion regulation; experience; extrastriate; extrastriate visual cortex; follow up assessment; follow-up; functional disability; functional improvement; functional outcomes; high risk; improved outcome; individualized medicine; neural; neurobehavioral; neuroimaging; neuromechanism; novel; personalized medicine; prospective; psychiatric symptom; recruit; reduce symptoms; response; sex; stressor; suicidal risk; therapy development; treatment strategy

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.

抽象的 尽管几十年来已有多种不同的抑郁症治疗方法，但全球 疾病负担稳步加重。抑郁症现已成为全世界残疾的主要原因之一。 目前抑郁症的治疗策略大部分仍处于反复试验阶段，只有不到 40% 的患者能够治愈 对特定的治疗有反应，并且即使继续治疗，这种反应也能维持一年。一个中央 改善这些结果的障碍是需要描述抑郁症的更好的表型，这些表型是 比当前的症状群更接近可修改的神经生物学目标 诊断代码。我们小组和其他人的研究结果表明，这样的一种表型涉及 在经历负面经历后倾向于感到愤怒、敌意和烦躁，并以积极的方式做出反应 攻击性的、过度敌对的方式（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、攻击性行为以及现实世界的人际交往和工作有关 功能障碍可能会加剧抑郁症状。该项目的主要目标是测试 一种新颖的模型，通过该模型，成年抑郁症患者的愤怒敌意水平较高与 异常神经功能和行为的特定模式，导致功能结果和未来不佳 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 将招募 100 名人口统计匹配、精神健康的个体。参与者将完成 临床、神经影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 天的生态瞬时评估协议。该项目将检查 1) 是否 愤怒的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 设置; 3）先验神经系统和行为的异常是否可以前瞻性地预测较差的真实情况 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，这项研究的结果有潜力 描述愤怒情绪升高的神经生物学基础、行为机制和现实世界后果 患有抑郁症的成年人之间存在敌意。未来的工作将旨在开发个性化治疗方法以针对 本研究中确定的神经机制是为了减轻症状并改善功能结果 愤怒敌意程度较高的患有抑郁症的成年人。