| Abstract | Background: Opportunities for research on the causes
and consequences of stress-related hippocampal atrophy
are limited in human psychiatric disorders. Therefore,
this longitudinal study investigated early life stress
and inherited variation in monkey hippocampal volumes.
Methods: Paternal half-siblings raised apart from one
another by different mothers in the absence of fathers were
randomized to 1 of 3 postnatal conditions that disrupted
diverse aspects of early maternal care (n=13 monkeys
per condition). These conditions were previously
shown to produce differences in social behavior, emotional
reactivity, and neuroendocrine stress physiology.
Hippocampal volumes were subsequently determined
in adulthood by high-resolution magnetic resonance imaging.
Results: Adult hippocampal volumes did not differ
with respect to the stressful postnatal conditions. Based
on paternal half-sibling effects, the estimated proportion
of genetic variance, ie, heritability, was 54% for hippocampal
size. Paternal half-siblings with small adult hippocampal
volumes responded to the removal of all
mothers after weaning with initially larger relative
increases in cortisol levels. Plasma cortisol levels 3 and 7
days later, and measures of cortisol-negative feedback in
adulthood were not, however, correlated with hippocampal
size.
Conclusions: In humans with mood and anxiety disorders,
small hippocampal volumes have been taken as
evidence that excessive stress levels of cortisol induce
hippocampal volume loss. Results from this study of
monkeys suggest that small hippocampi also reflect
an inherited characteristic of the brain. Genetically
informed clinical studies should assess whether inherited
variation in hippocampal morphology contributes
to excessive stress levels of cortisol through diminished
neuroendocrine regulation. |
