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 尽管数十年来已有多种不同的抑郁症治疗方法，但全球 疾病负担稳步增长。抑郁症现在是全球残疾的主要原因之一。 当前的抑郁症治疗策略在很大程度上是反复试验的，不到40％的患者 应对给定的治疗方法并维持这种反应一年，即使继续进行治疗。中央 改善这些结果的障碍是需要表征更好的抑郁疾病表型 与目前的症状星座相比，与可修改的神经生物学靶标更加一致 诊断代码。我们小组和其他人的发现表明，这样的表型涉及 在负面经历后经历愤怒，敌意和烦躁的倾向，并在 激进的，过于敌对的态度（以下表示愤怒的敌意）。我们的初步数据表明 愤怒的敌对表型与神经区域的特定功能改变有关 支持情绪处理和情绪调节。此外，愤怒的敌意似乎是强烈的 与挑衅以及现实世界际交往和工作相关的敌对，积极行为有关 功能障碍会加剧抑郁症状。该项目的主要目标是测试 新型模型通过，抑郁症患者中更高水平的愤怒敌意与 异常神经功能和行为的特定模式，导致功能不良和未来 症状。为了实现这些目标，至少有轻度抑郁症状的150名成年人（18-45岁）将 被招募，以及100个人口统计学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个，8个月和12个月的随访 评估和四个10天的生态瞬时评估方案。该项目将检查1）是否 愤怒的敌意与情绪处理和情绪调节中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侵略性行为有关 设置; 3）a-priori神经系统中的异常和行为的异常是否前瞻性地预测了较差的现实 在12个月的随访中，世界功能和精神病症状。该项目的目的与 国家心理健康研究所的战略目标。此外，这项研究的结果具有潜力 描述神经生物学基础，行为机制和现实世界的后果 抑郁症成年人的敌意。未来的工作将旨在开发个性化治疗，以针对 在本研究中确定的神经机制，以减轻症状并改善功能结果 抑郁症的成年人愤怒的敌意水平更高。