Preliminary evidence that hippocampal volumes in monkeys predict stress levels of adrenocorticotropic hormone.
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 (r(s) = .82, p = .0004) and hydrocortisone (r(s) = .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 (beta = -.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 (beta = -.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.
Lyons
David M
DM
Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, California 94305-5485, USA. dmlyons@stanford.edu
Parker
Karen J
KJ
Zeitzer
Jamie M
JM
Buckmaster
Christine L
CL
Schatzberg
Alan F
AF
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006854:Hydrocortisone / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012453:Saimiri; D012934:Social Isolation / Q000523:psychology; D013315:Stress, Psychological / Q000097:blood* / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone