Plasticity of the epigenome during early-life stress

Semin Cell Dev Biol. 2018 May;77:115-132. doi: 10.1016/j.semcdb.2017.09.033. Epub 2017 Oct 16.


Early life adversity remains a significant risk factor for the development of a host of negative behavioural and pathological outcomes in adulthood long after the stressor is over. Recent evidence indicates that these lasting effects of ELS may occur via alterations in the epigenetic landscape. Here, we review the main findings of the effects of early life adversity on DNA methylation, histone post-translational modification, and non-coding RNAs in the context of psychiatric disease in animal models and human cohorts. We specifically explore how early life adversity alters epigenetic patterns in both a global manner, and in specific candidate genes that play a role in relevant systems such as the hypothalamic-pituitary-adrenal axis, as well as neurotransmitter and neuroendocrine signalling. We also discuss how individual factors, such as genetics, sex, and age, as well as the type, and timing of early life adversity, can create differential susceptibility and significantly moderate outcomes. Although challenges remain in deciphering the complexity of how the early environment interacts with individual factors to determine epigenetic patterns, as well as how to translate these mechanistic findings into clinically relevant populations, the reviewed literature sheds light on the potential of the field to identify effective interventions for vulnerable individuals.

Keywords: Differential susceptibility; Early life adversity; Epigenetics; HPA axis; Psychopathology; Resilience.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • DNA Methylation / genetics
  • Disease Models, Animal
  • Epigenesis, Genetic / genetics*
  • Glutamic Acid / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / physiology
  • Mental Disorders / etiology*
  • Mental Disorders / genetics*
  • Mice
  • Pituitary-Adrenal System / physiology
  • Protein Processing, Post-Translational / genetics
  • Psychopathology
  • RNA, Untranslated / genetics
  • Rats
  • Resilience, Psychological*
  • Serotonin / metabolism
  • Signal Transduction / physiology
  • Stress, Psychological / genetics*
  • Stress, Psychological / psychology*
  • gamma-Aminobutyric Acid / metabolism


  • Brain-Derived Neurotrophic Factor
  • RNA, Untranslated
  • Serotonin
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • BDNF protein, human