Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy
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Brittany R Howell1, Kai M McCormack, Alison P Grand
1Department of Psychiatry & Behavioral Sciences, Emory University, 101 Woodruff Circle, WMB Suite 4000, Atlanta, GA 30322, USA. bcopp@emory.edu.
Insights
Infant maltreatment in rhesus monkeys leads to lasting white matter damage in adolescent brains, linked to early stress hormones. This early life stress impacts brain development and emotional regulation long-term.
Area of Science:
- Neuroscience
- Developmental Psychology
- Primatology
Background:
- Early adverse experiences, particularly disrupted mother-infant relationships, negatively affect primate socioemotional development.
- Childhood maltreatment in humans is linked to increased risk of psychopathologies.
- Neurodevelopmental alterations from early life stress are not fully understood.
Purpose of the Study:
- To investigate long-term effects of infant maltreatment on adolescent brain white matter integrity in a nonhuman primate model.
- To examine behavioral correlates and the relationship with early stress hormone levels.
Main Methods:
- Diffusion tensor imaging and tract-based spatial statistics were used to assess white matter integrity in maltreated and control adolescent rhesus monkeys.
- Basal plasma cortisol levels from infancy were correlated with white matter integrity.
- Social aggression was measured and correlated with white matter integrity.
Main Results:
- Maltreated adolescents showed reduced white matter structural integrity (fractional anisotropy) in key brain regions, including the corpus callosum, occipital white matter, and brainstem.
- Alterations in radial diffusivity suggest reduced myelin as the likely cause of tract integrity changes.
- Reduced white matter integrity was associated with elevated early-life plasma cortisol levels and increased social aggression.
Conclusions:
- Infant maltreatment has enduring effects on brain white matter structural integrity, impacting visual processing, emotional regulation, and sensorimotor integration.
- Elevated infant stress hormones correlate with long-term white matter structural changes in maltreated animals.
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.
