Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: Associations with high cortisol during infancy

Brittany R. Howell, Kai M. McCormack, Alison P. Grand, Nikki T. Sawyer, Xiaodong Zhang, Dario Maestripieri, Xiaoping Hu, Mar M. Sanchez

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Background: Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods: Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity. Results: We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression. Conclusions: These findings highlight the long-term impact of infant maltreatment on brain white matter structural integrity, particularly in tracts involved in visual processing, emotional regulation, and somatosensory and motor integration. They also suggest a relationship between elevations in stress hormones detected in maltreated animals during infancy and long-term brain white matter structural effects.

Original languageEnglish (US)
Article number3
JournalBiology of Mood and Anxiety Disorders
Issue number1
StatePublished - Dec 2 2013

Bibliographical note

Funding Information:
We would like to thank Anne Glenn, Richelle Scales, and the Animal/ Veterinary Care staff at the Yerkes National Primate Research Center Field Station for their invaluable help in collecting the data presented. We would also like to thank Dr. Gwena?lle Douaud (FMRIB) and Matt Glasser for their help in applying the TBSS methodology to monkeys. The project described was supported by Grant Numbers MH65046 (MMS), MH62577 (DM), P50 MH078105, MH091645, and F31 MH086203 (BRH) from the National Institute of Mental Health (NIMH) and NICHD055255 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, NICHD or the National Institutes of Health. The project was also funded by the National Center for Research Resources P51RR165 (YNPRC Base grant) and is currently supported by the Office of Research Infrastructure Programs/OD P51OD11132. The YNPRC is fully accredited by the American for the Assessment and Accreditation of Laboratory Care, International.

Publisher Copyright:
© 2013 Howell et al.


  • Adolescence
  • Diffusion tensor imaging
  • Early life stress
  • Rhesus monkeys


Dive into the research topics of 'Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: Associations with high cortisol during infancy'. Together they form a unique fingerprint.

Cite this