The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome

PSYCHONEUROENDOCRINOLOGY

卷:38

Article

Daskalakis, Nikolaos P.^1,2,3,4,5,6  Bagot, Rosemary C.^7,8  Parker, Karen J.⁹  Vinkers, Christiaan H.^10,11,12  de Kloet, E. R.^5,6 

[1] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY USA

[2] Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY USA

[3] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, PTSD Clin Res Program, Bronx, NY USA

[4] James J Peters Vet Affairs Med Ctr, Lab Clin Neuroendocrinol & Neurochem, Bronx, NY USA

[5] Leiden Univ, Leiden Acad, Ctr Drug Res, Div Med Pharmacol, Leiden, Netherlands

[6] Leiden Univ, Leiden Univ Med Ctr, Leiden, Netherlands

[7] Douglas Mental Hlth Univ Inst, Neurosci Div, Montreal, PQ, Canada

[8] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Fishberg Dept Neurosci, Lab Mol Psychiat, New York, NY USA

[9] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[10] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands

[11] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacol, Utrecht, Netherlands

[12] Univ Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

关键词: Vulnerability;    Resilience;    Stress adaptation;    Three hit;    HPA axis;    Developmental programming;    Epigenetics Genetic predisposition;    Early life environment;    Later life environment;   

DOI  :  10.1016/j.psyneuen.2013.06.008

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

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