5-羟色胺转运体基因和心脏事件的交互效应与负性情感反应的关系，及负性情感反应对急性冠脉综合征预后的影响

5-hydroxytrptamine transporter linked polymorphic region (5-HTTLPR) is the most investigated genetic variant in psychiatry, psychology, and neuroscience. There are many studies reported that individuals carrying short (S) allele of 5-HTTLPR exhibit elevated neuroticism, a personality trait involved in the propensity to depression. However, most studies are cross-section studies, from which cannot conclude causal relationship. This proposed study is a prospective cohort study. The participants are patients after their first onset of acute coronary syndrome (ACS). All participants are divided into 3 groups based on 3 genotypes of 5-HTTLPR: S/S, L/S, and L/L. They will be followed up until one and a half years after heart attack. We try to detect that which genotype is more likely to develop depression, anxiety, or burnout. Furthermore, to test the association between these negative affective responses due to heart attack and patients' recovery after ACS. Third, to observe whether negative affective responses can increase cortisol reactivity. Coronary heart disease (CHD) is a chronic disease resulting from a combination of multiple factors. The aim of this study is to explore the interaction of gene and chronic stress in the prognosis of CHD-This is a new research field at home and abroad.

5-HTT基因是目前研究证据最多的、与压力作用下的情绪反应关系密切的基因。5-HTT基因启动子区存在一个可变串联重复多态性，称为5-HTTLPR，短等位基因（S）和长等位基因（L）构成S/S，L/S，和L/L 三种基因型。大多数研究发现S等位基因携带者在压力作用下比较容易产生抑郁，但这些研究多为横断面研究，纵向研究并不多见。横断面研究不能推导因果关系，故本课题设计成一个前瞻性队列研究，研究对象是初次发生急性冠脉综合征的病人，把病人按照3种基因型分为3组，动态观察在急性心脏事件这一心理冲击后，某种基因型的病人是否更容易发生抑郁、焦虑、或倦怠，并进一步研究这些负性情感反应对病人预后的影响，以及负性情感反应能否激活下丘脑-垂体-肾上腺轴。冠心病是一个多因素共同作用所致的疾病，本课题的主旨是研究情绪相关基因和慢性压力的交互作用对冠心病预后的影响，这在国内外都属于比较新的研究领域。

负性情感反应和遗传因素可能与冠心病有密切关系。本课题以急性冠脉综合征（Acute myocardial infarction，ACS）的患者为研究对象，用专业量表评估其焦虑、抑郁和倦怠水平，随访1年，定期检测体力、生活质量和心率变异性（Heart rate variability，HRV）。取外周静脉血提取基因组DNA，PCR法确定5-羟色胺转运体基因启动子区可变数目串联重复多态性（5-hydroxytrptamine transporter linked polymorphic region，5-HTTLPR）。取少量头发，用高效液相色谱法测定患者的头发皮质醇浓度。经统计分析得到如下结果：①三种5-HTTLPR基因型（L/L、L/S、S/S）对ACS后的焦虑、抑郁和倦怠无明显影响；②抑郁和倦怠不利于ACS患者的体力恢复，焦虑对体力恢复的影响不明显；③焦虑、抑郁、倦怠均会降低ACS患者的生活质量，以抑郁和倦怠影响最大；④伴有抑郁或倦怠的ACS患者多项HRV频域指标下降，提示HRV下降可能是抑郁和倦怠导致ACS患者预后不良的原因之一，焦虑对HRV的影响不明显；⑤高倦怠和抑郁的ACS患者头发皮质醇浓度显著高于低倦怠和非抑郁的患者，焦虑与头发皮质醇浓度无显著相关关系。本研究结果提示抑郁和倦怠可能会使机体处于慢性应激状态，从而影响交感/副交感神经平衡，导致患者预后不良，如果在临床工作中对患者进行心理干预，减轻抑郁和倦怠程度，可能会改善ACS患者的预后。