初发淋巴瘤患者脑情绪环路功能失调与炎性活动失衡的交互作用机制的功能磁共振研究

The emotional-circuit, exerted itself in regulating the mood state and additionally affecting the cognitive function, serves as an executive functional network in affection and cognition. With the support of Excellent Youth Fund of Natural Science Foundation of China and the adoption of the cutting-edge MRI techniques, the applicant have revealed the mechanism that the disturbances in affection attributed greatly to the structural and functional changes of emotional-circuit. However, the molecular and physiological mechanisms underlying these imaging findings remain unclear. Recently, a serial of reviews and articles have been published in Nature and postulated that there might be potential association between the disturbance of inflammatory process and the abnormalities of emotional-circuit. Meanwhile, our previous studies have also found the association between anatomical brain changes and the single nucleotide polymorphisms (SNPs) relevant to the human leucocyte antigen (HLA). These evidences suggested a specific relationship between the functional disturbance of emotional-circuit and the imbalance between pro- or anti-inflammatory activities. Under the circumstance, patients with lymphoma are a typical cohort of subjects featured with significant disturbances in both emotion and immunity, and provide a good medium to investigate the question. Based on this, the applicant plans to combine the state-of-art MRI techniques, the analysis of humoral immune and the emotional and cognitive ratings, to explore the interactions between functional abnormalities of the emotional-circuit and the disturbance of inflammatory activity, both at baseline and after treatment, in the first episode lymphoma patients. Findings revealed by the present study are of great significance in elucidating the molecular and physiological mechanisms underlying the MRI biomarkers of the emotional-circuit.

“情绪环路”是调节人的情绪状态并显著影响认知功能的神经环路，在大脑的情感和认知调控中发挥着关键作用。申请人前期在国家自然科学基金优秀青年基金的支持下，采用磁共振新技术揭示了“情绪环路”结构、功能改变是情感障碍发生的脑机制。然而，这些影像改变的分子生理机制不清，近期在Nature上连续发表综合和论著提示了炎性活动的失衡与情绪环路损害的潜在联系。而申请人前期研究也发现了脑结构改变和与免疫相关的人类白细胞抗原相关基因变异之间存在关系。这些证据表明“情绪环路”功能失调与炎性活动失衡之间存在一定的关系。而淋巴瘤是临床上情绪障碍和炎性失衡的典型疾病。基于此，申请人拟通过将新型磁共振技术与体液免疫分析、情绪认知评估相结合，用于探索初发淋巴瘤患者治疗前后“情绪环路”功能改变与炎性活动失衡之间的交互作用机制，成果对揭示“情绪环路”磁共振影像生物表征的分子生理学机制具有重要意义。

申请人基于国内现有的影像学研究平台，创新性地结合结构与功能磁共振技术，探索不同细胞因子水平如何通过对脑功能和结构产生影响，从而导致行为症状的变化规律，并明确情绪状态的干预对细胞因子水平的影响。研究成果在精神病学领域和放射学领域顶级杂志American Journal of Psychiatry和Neuropsychopharmacology等上共发表SCI论文23篇，5篇IF>5。成果先后获得德国洪堡基金弗劳恩霍夫-贝塞尔研究奖、树兰医学青年奖，中华医学科技奖一等奖（排名第二），同时，申请人先后被授予教育部长江学者及中华医学会放射学分会杰出青年专家。