The Relationships of Peripheral Inflammation and Reward-Related Brain Function with Anhedonia, Somatic Symptoms and Functional Impairment in Adolescence

周围炎症和奖赏相关脑功能与青春期快感缺失、躯体症状和功能障碍的关系

• 批准号: 10830254
• 负责人: Ka-Yi Chat
• 金额: $ 3.34万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2024-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10830254
• 关键词: 16 year old; Active Learning; Adolescence; Adolescent; Affect; Alloys; Anhedonia; Basal Ganglia; Behavior assessment; Behavioral; Blood; Brain; Clinical; Clinical Psychology; Clinical Research; Cognition; Cognitive; Data Analyses; Depressed mood; Desire for food; Development; Diagnosis; Doctor of Philosophy; Educational workshop; Emotions; Enrollment; Fatigue; Functional disorder; Funding; Health; Immune system; Impaired cognition; Impairment; Individual; Inflammation; Inflammatory; Intervention; Link; Major Depressive Disorder; Measures; Mental Depression; Mentorship; Moods; National Institute of Mental Health; Neurobehavioral Manifestations; Nucleus Accumbens; Peripheral; Persons; Phenotype; Play; Population; Prefrontal Cortex; Prevalence; Principal Investigator; Process; Psychoneuroimmunology; Psychopathology; Research; Research Domain Criteria; Research Personnel; Rewards; Robin bird; Role; Schools; Scientist; Severities; Signal Transduction; Sleep; Social Functioning; Societies; Source; Symptoms; Testing; Training; Treatment outcome; United States National Institutes of Health; Universities; Visit; Work; associated symptom; brain abnormalities; child depression; clinical training; cost; depressive symptoms; design; disability; discounting; follow-up; functional MRI scan; functional disability; immune function; improved; inflammatory marker; insight; interest; invention; longitudinal, prospective study; mood symptom; neural; neural circuit; neuroimaging; pleasure; programs; prospective; recruit; reward processing; stem; trait; treatment response

PROJECT SUMMARY/ABSTRACT Major depression (MD) is a major source of disability affecting millions of people worldwide. Nevertheless, 30- 50% of the depressed population does not respond sufficiently to currently available treatments. Research suggests that the low treatment response rate may stem from elevated inflammatory signaling and abnormal reward processing that are not precisely targeted by currently available treatments. However, relationships of inflammation and abnormalities in reward function with a MD diagnosis are not detected consistently. Emerging research attributes the inconsistent findings to possible symptom-specific effects of inflammation and abnormalities in reward-related brain function. Indeed, inflammation and reward abnormalities have been linked with anhedonia, a cardinal feature of MD defined by decreased interest or pleasure in previously enjoyable activities, and with melancholic MD characterized by severe anhedonia, somatic symptoms, and functional impairment commonly modulated by reward function, whereas little evidence supports these abnormalities' association with cognitive symptoms (e.g., negative cognitions). This suggests a need to examine whether inflammation and reward abnormalities are relevant to only some MD symptoms. Further, inflammation may amplify the effect of reward dysfunction on these symptoms, given its role in altering reward-related dopaminergic tone and basal ganglion function. However, little work has tested these claims. Developmental stage also may contribute to inconsistent findings on the links of inflammation and reward function with MD. Adolescents may be particularly vulnerable, given the rapid changes in reward brain function and inflammatory phenotype. Thus, the proposed study seeks to test the hypotheses that elevated inflammation and low reward-related brain function, separately, and in interaction, are more strongly associated with anhedonia, somatic symptoms, and functional impairment than cognitive symptoms, during the vulnerable developmental stage of adolescence. The proposed study will recruit at least 192 14-16 year-olds varying in trait reward sensitivity who have enrolled in an assessment of peripheral inflammatory markers and reward-related neural activation and functional connectivity for my sponsor's NIMH-funded R01, prospective, longitudinal study of first-onset MD. A training plan has been designed that consists of formal coursework, workshops, experiential learning, and mentorship to develop the applicant's expertise in the pathophysiology of mood symptoms, psychoneuroimmunology, neuroimaging, and data analysis necessary to become an independent clinical neuroscientist. Utilizing the Research Domain Criteria perspective to examine inflammation, reward-related brain function, and individual MD symptoms, this study can yield greater insight into the role of inflammation and reward-related abnormalities in depressive psychopathology and clinical implications for interventions targeting inflammation and abnormal reward function. The proposed study will take place in Temple University's clinical psychology Ph.D. program, which has a successful track record of conducting impactful NIH-funded research and training clinical research scientists. 1

项目 摘要/摘要 重度抑郁症（MD）是影响全球数百万人的主要残疾来源。然而，30- 50％的抑郁人群对当前可用的治疗没有足够的反应。研究 表明低治疗缓解率可能源于炎症信号升高和异常 当前可用的治疗方法不是精确针对的奖励处理。但是，关系 没有始终检测到具有MD诊断的奖励功能的炎症和异常。新兴 研究将不一致的发现归因于炎症和 与奖励相关的大脑功能异常。实际上，炎症和奖励异常已连接 与Anhedonia一起，MD的主要特征是由以前令人愉快的兴趣或愉悦感定义 活动，以及以严重的抗anhedonia，躯体症状和功能性的忧郁MD为特征 损害通常受奖励功能调节，而几乎没有证据支持这些异常 与认知症状的关联（例如，负认知）。这表明需要检查是否 炎症和奖励异常仅与某些MD症状有关。此外，炎症可能 鉴于其在改变与奖励相关的多巴胺能的作用，扩大奖励功能障碍对这些症状的影响 音调和基础神经节功能。但是，很少的工作已经测试了这些主张。发展阶段也可能 促成关于炎症和奖励功能与MD的联系的不一致的发现。青少年可以 鉴于奖励大脑功能和炎症表型的快速变化，特别容易受到伤害。因此， 拟议的研究旨在测试升高炎症和与奖励相关的大脑升高的假设 单独和相互作用的功能与Anhedonia，躯体症状和 在青春期脆弱的发育阶段，功能障碍比认知症状。这 拟议的研究将招募至少有192 14-16岁的年龄在特质奖励敏感性方面，他们已经参加了 评估周围炎症标记和奖励相关的神经激活和功能连通性 对于我的发起人的NIMH资助的R01，前瞻性，对第一届MD的纵向研究。培训计划已经 设计由正式课程，讲习班，体验式学习和指导组成 申请人在情绪症状，心理肌免疫学，神经影像学和 成为独立的临床神经科学家所必需的数据分析。利用研究领域 检查炎症，与奖励相关的大脑功能和单个MD症状的标准观点， 研究可以更深入地了解抑郁症的炎症和与奖励相关的异常 精神病理学和临床意义针对针对炎症和异常奖励功能的干预措施。 拟议的研究将在Temple University的临床心理学博士学位上进行。程序，有一个 成功进行有影响力的NIH资助的研究和培训临床研究科学家的成功记录。 1