早期逆境与后期抑郁行为- - 基于非人灵长类的研究

Depression is a recurrent mental disorder characterized by lasting low mood which significantly affects a person's family and personal relationships. Chronic stress appears to have a strong causal association with depression. However, not all people who encounter stressful life events would be depressive. The link between genetic predisposition and life stressors in the etiology of depression has been demonstrate in a previous study, which showed that one or two copies of the short allele of a 5-HT transporter promoter polymorphism, in association with life stressor, significantly increased the risk for developing depression. However, many studies after that failed to replicate this result, or even yielded the contrary result.Thus, we assumed that besides the genotype other risk factors might influence the sensitivity to depression, for example, early adversity, which includes adverse experiences or stress events in early life. In fact,early adversity is a well established major risk factor for depression in late life by changing the plasticity of the brain. There is positive correlation between the frequencies, duration of early stress events with adult depression. In this study, we firstly use rhesus monkeys (Macaca mulatta), one of the non-human primate experimental animals which are evolutionally analogous to human being, to explore the relationship between early adversity and chronic stress-induced depression, This work would be very important for clarifying the relationship between early life stresses and late life depression induced by chronic stress. Furthermore, such research will allow for designing novel and effective interventions in childhood to prevent the effect of stress on depression and suggestive for developing non-human primate animal models for depression.

抑郁症是一种发病率很高的、反复发作的精神疾病，严重危害患者及家属的身心健康。慢性应激是诱发抑郁症的重要原因，但相当一部分个体在遭遇不幸或者重大应激事件后并不罹患抑郁症。有研究表明，携带五羟色胺转运体启动子区域短等位基因的个体在应激刺激诱导下更加容易患抑郁症，但相关研究结果并不统一，甚至还相互矛盾。所以我们推测：除了遗传因素之外，还存在其它因素对抑郁症的发病产生影响，例如早期逆境。早期逆境是指早期不幸经历或早期应激事件，它可以通过大脑的可塑性改变来增加抑郁症患病的风险，幼年经历应激性事件的强度和持续时间与成年抑郁症的发病率成正相关。在本研究中，我们将首次利用在进化系统上与人类较为相似的非人灵长类实验动物- - 猕猴来研究以母婴分离为代表的早期逆境与慢性应激诱导的抑郁症之间的关系，从而为人类抑郁症的早期干预提供理论依据，并为抑郁症的非人灵长类动物疾病模型开发提供基础。

抑郁症被称作精神感冒，核心症状包括情绪低落、快感缺失，已成为中国社会经济负担最重的第二大疾病，但其发病机理并不明确，虽然慢性应激是抑郁症的一大诱因，然而很多个体在经历慢性应激之后并不罹患抑郁症。因此，研究者提出抑郁症的素质-应激理论，认为在同样面临慢性应激的情况下，带有抑郁素质的个体更容易产生抑郁。因此，明确抑郁症的易感素质对其防治具有重大意义。素质受发育的影响。在发育早期，个体对环境因素最为敏感，此时如果经历早期逆境，将带来长期负面的影响。我们对青少年猕猴的研究发现，在同样慢性应激的诱导下，经历过出生后母婴分离猕猴的抑郁相关行为显著增加、压力应对系统HPA轴功能紊乱，而对照组的猕猴并未表现出上述行为和内分泌变化模式。我们认为，母婴分离组和对照组之间抑郁行为模式的差别可能来源于HPA轴的内分泌模式的差异，即早期母婴分离造成的HPA轴异常极有可能是抑郁症的易感素质之一。本项目为抑郁症模型开发和机制研究提供了基础理论指导。