Alloy Lauren B, Chat Iris K-Y, Grehl Mora M, Stephenson Auburn R, Adogli Zoe V, Olino Thomas M, Ellman Lauren M, Miller Gregory E, Nusslock Robin
Department of Psychology and Neuroscience, Temple University, USA.
Department of Psychology, Northwestern University, USA.
Brain Behav Immun Health. 2023 May 29;30:100643. doi: 10.1016/j.bbih.2023.100643. eCollection 2023 Jul.
Depression is associated with a reduced sensitivity to rewards and low reward-related brain function in cortico-striatal circuitry. A separate literature documents elevated peripheral inflammation in depression. Recently, integrated reward-inflammation models of depression have been proposed. These models draw on work indicating that peripheral inflammatory proteins access the brain, where they lower reward responsiveness. This blunted reward responsiveness is proposed to initiate unhealthy behaviors (substance use, poor diet), as well as sleep disruption and stress generation, which further heighten inflammation. Over time, dysregulation in reward responsiveness and immune signaling may synergize in a positive feedback loop, whereby dysregulation in each system exacerbates dysregulation in the other. Project RISE (Reward and Immune Systems in Emotion) provides a first systematic test of reward-immune dysregulation as a synergistic and dynamic vulnerability for first onset of major depressive disorder and increases in depressive symptoms during adolescence.
This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 300 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior major depressive disorder. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the low tail of the dimension in order to increase the likelihood of major depression onsets. At Time 1 (T1), T3, and T5, each a year apart, participants complete blood draws to quantify biomarkers of low-grade inflammation, self-report and behavioral measures of reward responsiveness, and fMRI scans of reward neural activity and functional connectivity. At T1-T5 (with T2 and T4 six months between the yearly sessions), participants also complete diagnostic interviews and measures of depressive symptoms, reward-relevant life events, and behaviors that increase inflammation. Adversity history is assessed at T1 only.
This study is an innovative integration of research on multi-organ systems involved in reward and inflammatory signaling in understanding first onset of major depression in adolescence. It has the potential to facilitate novel neuroimmune and behavioral interventions to treat, and ideally prevent, depression.
抑郁症与奖赏敏感性降低以及皮质-纹状体回路中与奖赏相关的脑功能低下有关。另一类文献记载了抑郁症患者外周炎症水平升高。最近，有人提出了抑郁症的综合奖赏-炎症模型。这些模型借鉴了相关研究成果，表明外周炎症蛋白可进入大脑，降低奖赏反应性。这种减弱的奖赏反应性被认为会引发不健康行为（物质使用、不良饮食）以及睡眠障碍和压力产生，进而进一步加剧炎症。随着时间的推移，奖赏反应性和免疫信号的失调可能会在一个正反馈回路中协同作用，即每个系统的失调都会加剧另一个系统的失调。RISE项目（情绪中的奖赏与免疫系统）首次系统地测试了奖赏-免疫失调作为青少年首次发作重度抑郁症和抑郁症状增加的一种协同且动态的易感性因素。
这项由美国国立精神卫生研究所资助的R01研究是一项为期3年的前瞻性纵向调查，研究对象为来自美国费城地区的约300名社区青少年。符合条件的参与者必须年龄在13至16岁之间，英语流利，且此前未曾患过重度抑郁症。他们是沿着自我报告的奖赏反应性的整个维度进行挑选的，在该维度的低分值端进行了过度抽样，以增加重度抑郁症发作的可能性。在第1时间点（T1）、第3时间点（T3）和第5时间点，每个时间点相隔一年，参与者进行血液抽取以量化低度炎症的生物标志物、奖赏反应性的自我报告和行为测量，以及奖赏神经活动和功能连接的功能磁共振成像扫描。在T1至T5期间（每年的时间段之间T2和T4相隔6个月），参与者还完成诊断访谈以及抑郁症状、与奖赏相关的生活事件和增加炎症的行为的测量。仅在T1评估逆境史。
这项研究创新性地整合了涉及奖赏和炎症信号传导的多器官系统研究，以理解青少年重度抑郁症的首次发作。它有可能促进新型神经免疫和行为干预措施的发展，用于治疗抑郁症，并理想地预防抑郁症。
