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Neurohormones, Neurodevelopment, and Psychosis 267and cortisol levels is not restricted to clinical populations. A study of both young(19-30 years) and older (59-76 years) healthy male subjects showed that hippocampalvolume was inversely associated with urinary cortisol and corticotropin(ACTH) levels, after controlling for cerebral vault size (Wolf, Convit, de Leon,Caraos, & Qadri, 2002).Extending these findings, we recently conducted an investigation of salivarycortisol and hippocampal volume in a group of healthy young males (mean age 25years; Tessner et al., unpublished paper). The study employed a double-blind crossoverdesign. There were two experimental conditions: placebo and hydrocortisone(cortisol) administration. Each subject was assessed under both conditions, with halfrandomly assigned to each of the two condition orders. The placebo or drug (100mg) was administered approximately 2 hours prior to MRI scanning. Saliva wassampled 12 times at regular intervals, prior to scanning. The average of all cortisolsamples was computed for each subject within condition. As expected, the administrationof hydrocortisone resulted in a significant increase in cortisol secretion aboveplacebo levels. Controlling for whole brain volume, there was a trend toward a significantinverse correlation between total hippocampal volume and mean cortisolin the placebo condition. In the hydrocortisone condition, the inverse correlationwas larger, and statistically significant (r = –.59, p < .05). These findings lend furthersupport to the link between hippocampal volume and cortisol secretion, andsuggest that the relation is more pronounced when cortisol secretion is elevated. Thusthe hippocampus may play a greater role in modulating HPA activity when it is elevatedabove baseline in response to challenge.As noted, the relation between cortisol levels and hippocampal volume appearsto be partially due to an adverse effect of elevated cortisol on hippocampal morphology.When compared to age-matched controls, patients receiving chroniccorticosteroid therapy have smaller hippocampal volumes and declarative memorydeficits (E. S. Brown et al., 2004). Also, functional neuroimaging of human subjectshas revealed that acute administration of cortisol selectively reduces hippocampalglucose utilization, suggesting that cortisol elevation has direct and acuteeffects on hippocampal function (de Leon et al., 1997).From the standpoint of preventive intervention, it is noteworthy that the adverseeffects of elevated cortisol on hippocampal structure and function may be reversible,under some circumstances. Sapolsky (1994) found reversible morphologicalchanges in animals exposed to moderate stress. This suggests hippocampal plasticityin animals, and recent findings suggest this is also the case in humans. For example,after cortisol levels decline to normal concentrations in treated Cushing’spatients, there is an increase in hippocampal volume that is accompanied by cognitiveimprovements (Starkman et al., 1999; Starkman, Giordani, Gebarski, Berent,& Schork & Berent, 2003). At this point, there is no data base for drawing inferencesabout the temporal course of plasticity; the hippocampal change may occurshortly after reductions in cortisol levels or extend over long time periods.