Early life stress and inherited variation in monkey hippocampal volumes

Background: Opportunities for research on the causes and consequences of st ress-related hippocampal atrophy are limited in human psychiatric disorders . Therefore, this longitudinal study investigated early life stress and inh erited 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 condi tions that disrupted diverse aspects of early maternal care (n=13 monkeys p er condition). These conditions were previously shown to produce difference s in social behavior, emotional reactivity, and neuroendocrine stress physi ology. Hippocampal volumes were subsequently determined in adulthood by hig h-resolution magnetic resonance imaging. Results: Adult hippocampal volumes did not differ with respect to the stres sful postnatal conditions. Based on paternal half-sibling effects, the esti mated proportion of genetic variance, ie, heritability, was 54% for hippoca mpal size. Paternal half-siblings with small adult hippocampal volumes resp onded to the removal of all mothers after weaning with initially larger rel ative increases in cortisol levels. Plasma cortisol levels 3 and 7 days lat er, and measures of cortisol-negative feedback in adulthood were not, howev er, correlated with hippocampal size. Conclusions: In humans with mood and anxiety disorders, small hippocampal v olumes 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 brai n. Genetically informed clinical studies should assess whether inherited va riation in hippocampal morphology contributes to excessive stress levels of cortisol through diminished neuroendocrine regulation.