Background
Hippocampal volumes previously determined in monkeys by magnetic resonance imaging
are used to test the hypothesis that small hippocampi predict increased stress levels
of adrenocorticotropic hormone (ACTH).
Methods
Plasma ACTH levels were measured after restraint stress in 19 male monkeys pretreated
with saline or hydrocortisone. Monkeys were then randomized to an undisturbed control
condition or intermittent social separations followed by new pair formations. After
17 months of exposure to the intermittent social manipulations, restraint stress tests
were repeated to determine test/retest correlations.
Results
Individual differences in postrestraint stress ACTH levels over the 17-month test/retest
interval were remarkably consistent for the saline (rs = .82, p = .0004) and hydrocortisone (rs = .78, p = .001) pretreatments. Social manipulations did not affect postrestraint stress ACTH
levels, but monkeys with smaller hippocampal volumes responded to restraint after
saline pretreatment with greater increases in ACTH levels with total brain volume
variation controlled as a statistical covariate (β = −.58, p = .031). Monkeys with smaller hippocampal volumes also responded with diminished
sensitivity to glucocorticoid feedback determined by greater postrestraint ACTH levels
after pretreatment with hydrocortisone (β = −.68, p = .010).
Conclusions
These findings support clinical reports that small hippocampi may be a risk factor
for impaired regulation of the hypothalamic-pituitary-adrenal axis in humans with
stress-related psychiatric disorders.
Key Words
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Article info
Publication history
Published online: June 16, 2007
Accepted:
March 16,
2007
Received in revised form:
March 7,
2007
Received:
September 26,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
