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，其点患病率为15-29%，是在一般人群中观察到的2 - 3倍。大量证据表明，炎症和促炎细胞因子活性的增加在患有炎症性疾病的人的抑郁和抑郁症状（如失眠、疲劳）的发生和持续中起着关键作用（Miller et al., 2009）。与此一致的是，实验工作表明，炎症挑战可以增加健康样本的抑郁情绪（Reichenberg et al., 2001）。基于这些发现，人们越来越关注炎症过程是否会以因果方式导致抑郁症，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（非炎症形式的）抑郁症的发病和延续中起着关键作用（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探索。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，“我觉得与他人脱节”），以及抑郁情绪增加（Eisenberger et al., 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经验的影响。本研究的首要目标是探索炎症引起的社会经验变化（例如，社会脱节的感觉）的经验和神经相关性，这可能为理解炎症和抑郁之间的关系提供一个关键的缺失环节。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6小时内进行监测。抽血以评估细胞因子水平以及自我报告的与社会脱节的感觉和抑郁情绪将每小时收集一次。此外，在细胞因子反应高峰时，参与者将完成神经成像会议，以检查炎症挑战对社会排斥和社会接受的神经敏感性的影响。据推测，随着时间的推移，内毒素会增加社会脱节的感觉，而产生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.