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Open Access Research

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

Brittany R Howell12*, Kai M McCormack23, Alison P Grand2, Nikki T Sawyer4, Xiaodong Zhang2, Dario Maestripieri5, Xiaoping Hu6 and Mar M Sanchez12

Author Affiliations

1 Department of Psychiatry & Behavioral Sciences, Emory University, 101 Woodruff Circle, WMB Suite 4000, Atlanta, GA 30322, USA

2 Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA

3 Department of Psychology, Spelman College, 350 Spelman Lane, Box 209, Atlanta, GA 30314, USA

4 Department of Natural Sciences, Clayton State University, 2000 Clayton State Boulevard, Morrow, GA 30260, USA

5 Department of Comparative Human Development, University of Chicago, 5730 South Woodlawn Avenue, Chicago, IL 60637, USA

6 Biomedical Imaging Technology Center, Emory University, 1760 Haygood Drive, Room W232, Atlanta, GA 30322, USA

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Biology of Mood & Anxiety Disorders 2013, 3:21  doi:10.1186/2045-5380-3-21

Published: 2 December 2013

Abstract

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.

Keywords:
Early life stress; Adolescence; Rhesus monkeys; Diffusion tensor imaging