Lasting epigenetic influence of early-life adversity on the BDNF gene

Biol Psychiatry. 2009 May 1;65(9):760-9. doi: 10.1016/j.biopsych.2008.11.028. Epub 2009 Jan 15.


Background: Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. With a rat model of infant maltreatment by a caregiver, we investigated whether early-life adversity leaves lasting epigenetic marks at the brain-derived neurotrophic factor (BDNF) gene in the central nervous system.

Methods: During the first postnatal week, we exposed infant rats to stressed caretakers that predominately displayed abusive behaviors. We then assessed DNA methylation patterns and gene expression throughout the life span as well as DNA methylation patterns in the next generation of infants.

Results: Early maltreatment produced persisting changes in methylation of BDNF DNA that caused altered BDNF gene expression in the adult prefrontal cortex. Furthermore, we observed altered BDNF DNA methylation in offspring of females that had previously experienced the maltreatment regimen.

Conclusions: These results highlight an epigenetic molecular mechanism potentially underlying lifelong and transgenerational perpetuation of changes in gene expression and behavior incited by early abuse and neglect.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn / genetics*
  • Animals, Newborn / metabolism*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cytidine / administration & dosage
  • Cytidine / analogs & derivatives
  • Cytidine / pharmacology
  • DNA Methylation / drug effects
  • Epigenesis, Genetic*
  • Female
  • Gene Expression
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Male
  • Maternal Behavior
  • Models, Animal
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Long-Evans
  • Stress, Psychological / genetics*


  • Brain-Derived Neurotrophic Factor
  • Cytidine
  • pyrimidin-2-one beta-ribofuranoside