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

描述（由申请人提供）：本申请提交给NIMH DATR情绪/睡眠研究计划A2-AID。抑郁症在炎症性疾病患者中的发生率很高，点患病率为15- 29%，是一般人群中观察到的患病率的2 - 3倍。大量证据表明，炎症和促炎性细胞因子活性的增加在患有炎性疾病的那些人中抑郁和抑郁症状（例如失眠、疲劳）的发作和持续中起关键作用（米勒et al.，2009年）。与此一致，实验工作已经表明，炎症激发可以增加原本健康的样品中的抑郁情绪（赖兴贝格等人，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因果关系的方式导致抑郁症，以及这些影响如何发生。 鉴于炎症过程会引发社交退缩（Dantzer，2001年;哈特，1988年），再加上证据表明，“社会脱节”的感觉发挥了关键作用，在发病和延续的抑郁症（非炎症形式）（Heinrich & Gullone，2006年），令人惊讶的是，炎症的社会心理后果及其对抑郁症的影响尚未得到更充分的探讨。在这里，我们认为炎症可能会增加社会脱节的感觉，这些社会心理变化可能是炎症相关抑郁症的重要因素。事实上，初步数据表明，实验诱导的炎症挑战（内毒素）导致自我报告的社会脱节感增加（例如，“我感到与他人脱节”），除了抑郁情绪的增加（艾森伯格等人，2009年b）。然而，除了这些发现之外，还没有研究探讨炎症过程对人类社会经验的影响。这项提议的首要目标是探索炎症诱导的社会经验变化的经验和神经相关性（例如，社会脱节的感觉），这可能为理解炎症和抑郁症之间的关系提供了关键的缺失环节。 受试者（n=100）将被随机分配接受内毒素或安慰剂，然后在接下来的6小时内进行监测。每小时采集一次血液，以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。此外，在细胞因子反应达到峰值时，参与者将完成神经影像学检查，以检查炎症激发对社会排斥和社会接受的神经敏感性的影响。据推测，内毒素会随着时间的推移增加社会脱节的感觉，并且引起这些感觉的潜在神经敏感性（例如，对社会排斥的神经敏感性增加;对社会接受的神经敏感性降低）将有助于炎症诱导的抑郁情绪。

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.