Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms

炎症引起的抑郁情绪：社会神经认知机制的作用

• 批准号: 8429495
• 负责人: Naomi Ilana Eisenberger
• 金额: $ 39.49万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429495
• 关键词: Accounting; Affective; Anterior; Behavioral; Blood; Coupled; Cytokine Gene; Data; Depressed mood; Depressive disorder; Disease; Distress; Dorsal; Endotoxins; Exposure to; Fatigue; Feeling; Female; Functional Magnetic Resonance Imaging; General Population; Genes; Genetic Polymorphism; Happiness; Hour; Human; Immune; Individual; Individual Differences; Inflammation; Inflammatory; Insula of Reil; Interleukin-6; Link; Loneliness; Measures; Mediating; Mental Depression; Methodology; Monitor; Moods; National Institute of Mental Health; Neurocognitive; Opioid; Opioid Receptor; Outcome; Participant; Pathway interactions; Patient Self-Report; Patients; Placebos; Play; Prevalence; Process; Randomized; Research; Role; Sampling; Sleep; Sleeplessness; Social Change; Social Perception; Social isolation; Social support; Testing; Time; Variant; Ventral Striatum; Withdrawal; Work; base; cingulate cortex; cytokine; depressive symptoms; experience; indexing; innovation; insight; interest; neuroimaging; novel; programs; psychologic; public health relevance; relating to nervous system; response; reward processing; social

DESCRIPTION (provided by applicant): This application is submitted to the NIMH DATR Mood/Sleep Research Program A2-AID. Depressive disorders occur at a high rate in patients with inflammatory disorders, with a point prevalence of 15-29%, which is two to three times greater than that observed in the general population. Substantial evidence has shown that inflammation and increases in proinflammatory cytokine activity play a critical role in the onset and perpetuation of depression and depressive symptoms (e.g. insomnia, fatigue) in those who are co-morbid for inflammatory disorders (Miller et al., 2009). Consistent with this, experimental work has shown that an inflammatory challenge can increase depressed mood in an otherwise healthy sample (Reichenberg et al., 2001). Based on these findings, there has been a growing interest in whether inflammatory processes can contribute to depression in a causal manner and how these effects might occur. Given the observation that inflammatory processes trigger social withdrawal (Dantzer, 2001; Hart, 1988), coupled with evidence that feelings of 'social disconnection' play a critical role in the onset and perpetuation of (non-inflammatory forms of) depression (Heinrich & Gullone, 2006), it is surprising that the social psychological consequences of inflammation and their contribution to depression have not been more fully explored. Here, we suggest that inflammation may increase feelings of social disconnection and that these social psychological changes may be an important contributor to inflammation-associated depression. Indeed, preliminary data demonstrated that an experimentally-induced inflammatory challenge (endotoxin) led to increases in self-reported feelings of social disconnection (e.g., "I feel disconnected from others") in addition to increases in depressed mood (Eisenberger et al., 2009b). Aside from these findings, however, there are no studies that have explored the effect of inflammatory processes on social experience in humans. The over- arching objective of this proposal is to explore the experiential and neural correlates of inflammatory- induced changes in social experience (e.g., feelings of social disconnection), which may provide a critical missing link in understanding the relationship between inflammation and depression. Participants (n=100) will be randomly assigned to receive either endotoxin or placebo and will then be monitored for the next six hours. Blood draws to assess cytokine levels as well as self-reported feelings of social disconnection and depressed mood will be collected hourly. In addition, at the time of peak cytokine response, participants will complete a neuroimaging session to examine the effect of inflammatory challenge on neural sensitivity to social rejection and social acceptance. It is hypothesized that endotoxin will increase feelings of social disconnection over time, and that the underlying neural sensitivities that give rise to these feelings (e.g., increased neural sensitivity to social rejection; decreased neural sensitivity to social acceptance) will contribute to inflammatory-induced depressed mood.

描述(由申请者提供)：此申请提交给NIMH DATR情绪/睡眠研究计划A2-AID。在炎症性疾病患者中，抑郁障碍的发生率很高，其时点患病率为15%-29%，比普通人群的患病率高出两到三倍。大量证据表明，炎症和促炎细胞因子活性的增加在合并炎症性疾病的患者中抑郁和抑郁症状(如失眠、疲劳)的发生和持续起着关键作用(Miller等人，2009年)。与此一致的是，实验工作表明，发炎挑战可以增加原本健康的样本的抑郁情绪(Reichenberg等人，2001年)。基于这些发现，人们越来越感兴趣的是炎症过程是否会以一种因果的方式导致抑郁症，以及这些影响是如何发生的。鉴于观察到炎症过程会引发社交退缩(Dantzer，2001；Hart，1988)，再加上有证据表明，“社会脱节”的感觉在(非炎症性形式的)抑郁症的发生和持续中起着关键作用(Heinrich&Gullone，2006)，令人惊讶的是，炎症的社会心理后果及其对抑郁症的贡献尚未得到更充分的研究。在这里，我们认为炎症可能会增加社会疏离感，这些社会心理变化可能是炎症相关抑郁的重要因素。事实上，初步数据表明，实验诱导的炎症挑战(内毒素)除了增加抑郁情绪外，还会导致自我报告的社交脱节感觉增加(例如，“我感觉与他人脱节”)(Eisenberger等人，2009b)。然而，除了这些发现之外，还没有研究探索炎症过程对人类社会体验的影响。这一建议的总体目标是探索炎症引起的社会体验变化(例如，社会脱节的感觉)的经验性和神经性相关性，这可能是理解炎症和抑郁之间关系的关键缺失环节。参与者(n=100)将被随机分配接受内毒素或安慰剂，然后在接下来的六个小时内接受监测。抽血评估细胞因子水平，以及自我报告的社交脱节和抑郁情绪的感觉将每小时收集一次。此外，在细胞因子反应达到高峰时，参与者将完成神经成像课程，以检查炎症挑战对神经对社会拒绝和社会接受的敏感性的影响。假设随着时间的推移，内毒素会增加社交脱节的感觉，而引起这些感觉的潜在神经敏感性(例如，对社会拒绝的神经敏感性增加；对社会接受的神经敏感性降低)将有助于炎症性诱导的抑郁情绪。

项目成果

An empirical review of the neural underpinnings of receiving and giving social support: implications for health.

• DOI: 10.1097/psy.0b013e31829de2e7
• 发表时间: 2013-07
• 期刊: Psychosomatic medicine
• 影响因子: 3.3
• 作者: Eisenberger NI

Ventromedial prefrontal cortex activity differentiates sick from healthy faces: Associations with inflammatory responses and disease avoidance motivation.

腹内侧前额叶皮层活动区分病人和健康的面孔：与炎症反应和疾病回避动机的关联。

• DOI: 10.1016/j.bbi.2021.11.011
• 发表时间: 2022
• 期刊: Brain, behavior, and immunity
• 作者: Leschak,CarrianneJ;Hornstein,EricaA;ByrneHaltom,KateE;Johnson,KerriL;Breen,ElizabethC;Irwin,MichaelR;Eisenberger,NaomiI
• 通讯作者: Eisenberger,NaomiI

Social ties and health: a social neuroscience perspective.

• DOI: 10.1016/j.conb.2013.01.006
• 发表时间: 2013-06
• 期刊: Current opinion in neurobiology
• 影响因子: 5.7
• 作者: Eisenberger NI

Frontostriatal functional connectivity underlies self-enhancement during social evaluation.

• DOI: 10.1093/scan/nsab139
• 发表时间: 2022-08-01
• 期刊: SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
• 影响因子: 4.2
• 作者: Parrish, Michael H.;Dutcher, Janine M.;Muscatell, Keely A.;Inagaki, Tristen K.;Moieni, Mona;Irwin, Michael R.;Eisenberger, Naomi, I
• 通讯作者: Eisenberger, Naomi, I

Effects of inflammation on social processes and implications for health.

• DOI: 10.1111/nyas.13864
• 发表时间: 2018-09
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Moieni M;Eisenberger NI
• 通讯作者: Eisenberger NI