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) 是影响全世界数百万人的残疾的主要根源。尽管如此，30- 50% 的抑郁症患者对当前可用的治疗没有足够的反应。研究 表明治疗反应率低可能源于炎症信号传导升高和异常 目前可用的治疗方法并未精确针对奖励处理。然而，关系 MD 诊断中的炎症和奖赏功能异常并未得到一致检测。新兴 研究将不一致的发现归因于炎症和可能的症状特异性影响 奖励相关的大脑功能异常。事实上，炎症和奖赏异常之间存在联系 快感缺失，这是 MD 的一个主要特征，定义为对先前享受的事物的兴趣或快乐减少 活动，以及以严重快感缺失、躯体症状和功能障碍为特征的忧郁型MD 损伤通常由奖赏函数调节，但很少有证据支持这些异常。 与认知症状（例如消极认知）的关联。这表明需要检查是否 炎症和奖赏异常仅与某些 MD 症状相关。此外，炎症可能 考虑到奖赏功能障碍在改变奖赏相关的多巴胺能方面的作用，放大了奖赏功能障碍对这些症状的影响 音调和基底神经节功能。然而，很少有工作验证这些说法。发育阶段也可能 导致炎症和奖赏功能与 MD 之间联系的不一致研究结果。青少年可能会 鉴于大脑奖赏功能和炎症表型的快速变化，他们特别容易受到伤害。因此， 这项拟议的研究旨在检验以下假设：炎症增加和与奖励相关的大脑水平降低 功能，无论是单独的还是相互作用的，都与快感缺乏、躯体症状和 在青春期的脆弱发展阶段，功能障碍多于认知症状。这 拟议的研究将招募至少 192 名 14-16 岁的特质奖励敏感度各异的青少年，他们已经参加了 评估外周炎症标志物和奖励相关的神经激活和功能连接 我的资助者的 NIMH 资助的 R01 是首次发病 MD 的前瞻性纵向研究。培训计划已经制定 设计包括正式课程、研讨会、体验式学习和指导，以发展 申请人在情绪症状的病理生理学、心理神经免疫学、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、奖赏相关脑功能和个体 MD 症状的标准视角，这 研究可以更深入地了解炎症和奖赏相关异常在抑郁症中的作用 针对炎症和异常奖赏功能的干预措施的精神病理学和临床意义。 拟议的研究将在天普大学临床心理学博士课程中进行。程序，其中有一个 在进行有影响力的 NIH 资助研究和培训临床研究科学家方面拥有成功的记录。 1