The relationship between stress induced cortisol levels and memory differs between men and women
Introduction
Epidemiological studies suggest that women have a higher incidence of several psychiatric disorders in which hypothalamus pituitary adrenal (HPA) axis dysregulations might be involved as causal or modulatory factors (e.g. post-traumatic stress disorder, major depression and Alzheimer's disease (Jorm et al., 1987, Breslau et al., 1997, Desai and Jann, 2000). Beside other research strategies, the investigation of gender differences in the response to stress might help to elucidate some of the underlying mechanisms responsible for these findings.
Exposure to stress influences cognition in animals and humans and it has been demonstrated that the stress-induced release of glucocorticoids (GCs; corticosterone in rats, cortisol in humans) is among other factors like epinephrine or CRH responsible for these effects. Studies in rodents have revealed that GCs enhance or impair performance dependent on the specific memory type tested and on the timing of the stress exposure, respectively (Diamond et al., 1996, Lupien and McEwen, 1997, de Quervain et al., 1998, De Kloet et al., 1999, Roozendaal, 2000). Experimental studies in humans have repeatedly shown, that GC administration can interfere with performance in working memory as well as declarative memory tasks, (Wolkowitz et al., 1990, Kirschbaum et al., 1996, Newcomer et al., 1999, Lupien et al., 1999, de Quervain et al., 2000, Wolf et al., 2001). Even though the data are not entirely consistent it appears that acute GC treatment impairs working memory (Lupien et al., 1999, Wolf et al., 2001) and delayed recall of declarative material (de Quervain et al., 2000, Wolf et al., 2001). Prolonged treatment (several days) seems to be needed in order for declarative learning deficits to occur (Newcomer et al., 1994, Newcomer et al., 1999, Schmidt et al., 1999, Young et al., 1999). In line with these pharmacological studies, memory impairing effects have been observed in young and elderly subjects after exposure to psychosocial laboratory stressors (Kirschbaum et al., 1996, Lupien et al., 1997, Wolf et al., 1999).
Only a few studies have tried to investigate whether memory processes of women and men might differ in their susceptibility to acute stress. A recent animal study strongly suggests that gender plays an important role in the effects of stress on cognition. Woods and Shors reported that stress enhanced classical conditioning in male rats, whereas it impaired it in female rats (Wood and Shors, 1998). In humans, an epidemiological study observed that higher basal cortisol levels were associated with poorer memory in elderly women, but not men (Seeman et al., 1997), suggesting, that elderly women are more susceptible to the effects of glucocorticoids. Similarly an experimental study in elderly humans found that exposure to a laboratory stressor impaired the recall of previously learned material more strongly in elderly women when compared to elderly men (Wolf et al., 1999). Most of the prior human studies investigating young subjects only studied men or the investigated populations were too small to detect gender differences (Kirschbaum et al., 1996, Lupien et al., 1997, Lupien et al., 1999). Moreover studies which included women did not control for phase of the menstrual cycle and/or the use of oral contraceptives (Newcomer et al., 1999, de Quervain et al., 2000).
In a previous study from this laboratory, it was observed that the stress-induced cortisol increase was negatively correlated with the memory performance after cessation of the stressor (Kirschbaum et al., 1996). Those subjects, who reacted with a strong cortisol increase performed more poorly in the memory task, than those subjects showing only a mild cortisol response. This pilot study did not include an unstressed control group and also did not consist of enough female subjects in order to address the issue of possible gender differences. The study reported here was therefore designed to first test the hypothesis, that subjects exposed to psychosocial stress perform poorer in a memory test than subjects from a control group, secondly to investigate whether the stress-induced cortisol increase is a predictor of memory performance after the stressor, and thirdly to explore the possibility that the relationship between the stress-induced cortisol increase and memory might differ between women and men.
Section snippets
Subjects
Participants of a larger study, which investigated endocrine response patterns to psychosocial stress exposure were also tested for memory performance. Smokers, subjects suffering from acute or chronic hormonal dysregulations, atopic-, psychosomatic-, or psychiatric diseases were excluded. All subjects reported to be free of medication. Before entering the study all participants received oral as well as written information about the study, provided written consent and underwent a comprehensive
Cortisol reaction to the stressor
Free cortisol levels doubled in response to the TSST from 10.4±1.1 nmol/l to 20.9±2.3 nmol/l. The net cortisol increase was 10.3±2.3 nmol/l in women (baseline: 8.6±1.1 nmol/l; post-stress: 18.9±2.5 nmol/l) and 11.0±4.2 nmol/l in men (baseline: 13.5±2.2 nmol/l; post-stress: 24.5±4.7 nmol/l). ANOVA indicated a significant main effect of “stress” (F(1,20)=23.84, P<0.001), in the absence of a gender main effect or a gender by stress interaction (both P values>0.10).
Memory performance: comparison between the stressed group and the control group
As a group, subjects exposed to
Discussion
In the present experiment, exposure to psychosocial stress in the laboratory did not impair recall of a word-list when the stress group was compared to a non-stressed control group. Even though the stressor lead to a two-fold cortisol increase, peak cortisol levels were still much lower than those observed in previous pharmacological studies (e.g. (Kirschbaum et al., 1996 (experiment II); de Quervain et al., 2000). It could be speculated that more pronounced stress-induced cortisol increases
Acknowledgments
This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) Ki 537/9-1, He1013/13-1, WO 733/2-1.
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