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Early Life Stress and Inherited Variation in Monkey Hippocampal Volumes
David M. Lyons, PhD;
Chou Yang, MA;
Anne M. Sawyer-Glover, RT(R)(MR);
Michael E. Moseley, PhD;
Alan F. Schatzberg, MD
Arch Gen Psychiatry. 2001;58:1145-1151.
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.
From the Departments of Psychiatry and Behavioral Science (Drs Lyons
and Schatzberg and Mr Yang) and Radiology (Ms Sawyer-Glover and Dr Moseley),
Stanford University Medical School, Stanford, Calif.
Corresponding author: David M. Lyons, PhD, Department of Psychiatry
and Behavioral Science, 1201 Welch Rd, Medical School Laboratory Surge Bldg,
Room P104–Mail Code 5485, Stanford University School of Medicine, Stanford,
CA 94305-5485 (e-mail: dmlyons{at}stanford.edu).
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