ReviewPsychoneuroendocrinology2013
The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.
Review in Psychoneuroendocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04165473 (A Training Program for Developing Social- and Personal Resources and Its Effects on Emotional, Physical and Social Wellbeing in Adults), which is not on this map. Cited by 248 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Training Program for Developing Social- and Personal Resources and Its Effects on Emotional, Physical and Social Wellbeing in Adults
Who cites it
248 citing papers in PubMed, 3 syntheses or guidelines pooled it, 575 citations in OpenAlex.
- From placenta to the foetus: a systematic review of in vitro models of stress- and inflammation-induced depression in pregnancy.Molecular psychiatry · 2025Pooled it
- Prenatal stress and externalizing behaviors in childhood and adolescence: A systematic review and meta-analysis.Psychological bulletin · 2024Pooled it
- Auditory verbal hallucinations and continuum models of psychosis: A systematic review of the healthy voice-hearer literature.Clinical psychology review · 2017Pooled it
- Do weighted blankets improve sleep among children with a history of maltreatment? A randomized controlled crossover trial.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2024Trial
- The prospective association between stressful life events and inflammation among adolescents with a history of early institutional rearing.Development and psychopathology · 2020Trial
- Mapping links between childhood maltreatment and biopsychosocial health in pregnancy: a network analysis.Archives of women's mental health · 2026Article
- Childhood socioeconomic status and changes in biological aging across mid-to-later life.Social science & medicine (1982) · 2026Article
- Revisiting 'environmental effects': Directions for multidisciplinary investigations of air quality and psychopathology.Clinical psychological science : a journal of the Association for Psychological Science · 2026Article
- Is there a bidirectional relationship between the number of unhealthy lifestyle factors and depressive symptoms in adolescents? Evidence from a longitudinal study.BMC medicine · 2026Article
- Maternal deprivation and adolescent alcohol exposure induce sex-dependent alterations in stress-related behavior and lipid signaling in rats.Biology of sex differences · 2026Article
- Early-life adversity in rodents: Experimental design is of the essence.Neurobiology of stress · 2026Article
- From teratogens to trajectories: Integrating teratology and Developmental Origins of Health and Disease (DOHaD) frameworks for a new take on fetal alcohol spectrum disorders (FASD).Neurobiology of stress · 2026Article
- Consistent changes in global gene expression patterns despite strong variation in individual gene expression in the male mouse hippocampus following early life stress.Neurobiology of stress · 2026Article
- Science with Seymour Levine: on glucocorticoid action from birth to senescence.Neurobiology of stress · 2026Article
- Environmental enrichment as an intervention to prevent behavioral and neurobiological consequences of maternal separation in rodents: a scope review.Neurobiology of stress · 2026Article
- Effects of early life adversity on socially learned analgesia and empathy in virtual reality.NPJ digital medicine · 2026Article
- Exploring Trajectories of Anxiety Symptoms in Autistic and Non-Autistic Youth over Adolescence Using Parent- and Self-Report Measures.Research in autism · 2026Article
- Stress-diathesis based predictors of depression and anxiety trajectories in adolescence: a population-based longitudinal cohort study.Psychological medicine · 2026Article
- Adrenarche as a regulator of sensitivity to early adversity.Journal of neuroendocrinology · 2026Review
- Divergent Inflammatory Profiles but No Predictive Biomarkers of Psychiatric Sequelae After Viral Infection: A 12-Month Cohort Study.International journal of molecular sciences · 2026Article
188 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.