The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.
The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.
复制标题
DOI：
10.1016/j.psyneuen.2013.06.008
复制
发表时间：
2013-09
影响因子：
3.7
通讯作者：
de Kloet, E. R.
中科院分区：
文献类型：
--
作者：
Daskalakis, Nikolaos P.;Bagot, Rosemary C.;Parker, Karen J.;Vinkers, Christiaan H.;de Kloet, E. R.
关键词：
早年的应激经历可以调节特定大脑回路的遗传编程，这些回路是行为适应晚年应激经历的情感和认知方面的基础。尽管这种由经验相关因素产生的编程效应是心理健康的一个重要决定因素，但其结果取决于认知输入，因此取决于个人对特定环境背景的分配。从这个角度，我们将通过对啮齿动物、非人类灵长类动物和人类的研究，强调三次打击的概念，即对与压力相关的精神障碍的脆弱性和恢复力，该概念基于围产期和青少年大脑发育的关键阶段的基因-环境相互作用。三次打击(即HIT-1：遗传易感性，HIT-2：早期生活环境，HIT-3：晚年环境)的概念适应了累积应激假设，即在给定的背景下，当未能应对逆境时，脆弱性会增强。或者，这个概念还指向个体的预测适应能力，这是压力接种和匹配/不匹配假设的基础。后一种假设认为，相对温和的早期生活逆境经历为未来做准备，并促进对以后生活中类似挑战的韧性；当早期生活经历和后期生活经历之间出现不匹配时，应对能力受到影响，脆弱性增强。对于理解个体如何为即将到来的生活做好准备并保持弹性，或者在看似相同的情况下无法应对并屈服于与压力相关的精神障碍，三次打击的概念是基本的。
Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual’s predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances.
登录
查看更多内容
影响因子：
11
作者：
通讯作者：
--
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
DOI：
10.1073/pnas.95.9.5335
发表时间：
1998-04-28
影响因子：
11.1
作者：
Caldji, C;Tannenbaum, B;Meaney, MJ
通讯作者：
Meaney, MJ
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH