Differential Susceptibility of the Developing Brain to Contextual Adversity and Stress

Neuropsychopharmacology. 2016 Jan;41(1):142-62. doi: 10.1038/npp.2015.294. Epub 2015 Sep 22.


A swiftly growing volume of literature, comprising both human and animal studies and employing both observational and experimental designs, has documented striking individual differences in neurobiological sensitivities to environmental circumstances within subgroups of study samples. This differential susceptibility to social and physical environments operates bidirectionally, in both adverse and beneficial contexts, and results in a minority subpopulation with remarkably poor or unusually positive trajectories of health and development, contingent upon the character of environmental conditions. Differences in contextual susceptibility appear to emerge in early development, as the interactive and adaptive product of genetic and environmental attributes. This paper surveys what is currently known of the mechanisms or mediators of differential susceptibility, at the levels of temperament and behavior, physiological systems, brain circuitry and neuronal function, and genetic and epigenetic variation. It concludes with the assertion that differential susceptibility is inherently grounded within processes of biological moderation, the complexities of which are at present only partially understood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / metabolism*
  • Brain / pathology
  • Disease Susceptibility / metabolism
  • Disease Susceptibility / pathology
  • Disease Susceptibility / psychology
  • Humans
  • Individuality*
  • Risk Factors
  • Social Environment*
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology
  • Stress, Psychological / psychology
  • Temperament / physiology*