Original articleSex differences in stress responses: social rejection versus achievement stress
Introduction
One of the most consistent findings in the epidemiology of depression is women’s greater rates of unipolar depression Boyd and Weissman 1981, Nolen-Hoeksema 1987, Nolen-Hoeksema 1990, Weissman and Klerman 1977. Across nations and cultures, women of reproductive age are approximately 2 times as likely to suffer from depressive syndromes and symptoms as men (Nolen-Hoeksema 1987). Although numerous theories to explain sex differences in depression have been proposed, adequate evidence in support of most theories has been lacking.
A large body of evidence has shown links between depression, psychological stress, and alterations in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis. Stressful life events and early adverse experiences, particularly when superimposed on genetic proclivities, have been consistently linked to the onset of depression Hammen et al 2000, Heim and Nemeroff 1999, Kaufman et al 2000, Kendler et al 1993, Kendler et al 1995, Kessler and Magee 1993, McCauley et al 1997. Similar alterations along the LHPA axis may underlie links between stress and depression. Acutely, perception of stress leads to activation of various central pathways that culminate in the release of corticotropin releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus. The release of CRH triggers a cascade of events resulting in the release of glucocorticoids from the adrenal cortex. Chronically, stress can lead to more permanent alterations along the LHPA axis, including both hypo- and hyperreactivity Chrousos and Gold 1992, Heim et al 2000. Similarly, depression has been associated with multiple abnormalities along the LHPA axis, including increased basal cortisol levels Halbreich et al 1985, Rubin et al 1987, nonsuppression in response to dexamethasone (suggesting blunted negative feedback; APA 1987, Carroll 1982, Carroll et al 1981, blunted adrenocorticotropin hormone (ACTH) response to CRH (Holsboer et al 1987) and increased central CRH drive, as evidenced by elevated CRH in cerebrospinal fluid Nemeroff et al 1984, Nemeroff et al 1991, and reduced CRH receptor binding sites in the frontal cortex (Nemeroff et al 1988). Given links between stress, LHPA dysregulation, and depression, we propose that sex differences in HPA responses to stress may be one mechanism underlying sex differences in depression.
Preclinical research has shown consistent sex differences in HPA responses. Similar to depressed humans, female rats consistently show greater basal corticosterone levels compared with male rats Allen-Rowlands et al 1980, Atkinson and Waddell 1997, Chisari et al 1995, Critchlow et al 1963, Griffin and Whitacre 1991, Hiroshige et al 1973, Kitay 1961, Kitay 1963. In response to both acute and chronic stressors, female rats also have consistently shown greater increases in both ACTH and corticosterone compared with males Armario et al 1995, Galea et al 1997, Haleem et al 1988, Handa et al 1994a, Kant et al 1983, Lesniewska et al 1990, Rivier 1999. Finally, recent research has also shown sex differences in central components of the HPA responses to stress, including expression of corticosteroid receptors and dendritic atrophy of the CA3 pyramidal neurons Galea et al 1997, Karandrea et al 2000.
Although women’s greater HPA reactivity in preclinical studies has been posited as relevant to greater rates of depression in women (Haleem et al 1988), the direction of sex differences in human HPA regulation is, if anything, reversed. In response to laboratory challenges including public speaking and mental arithmetic before an audience Kirschbaum et al 1992, Kirschbaum et al 1999, Kudielka et al 1998 as well as “real-world” examination stress (Frankenhaeuser et al 1978), male subjects have generally shown greater cortisol and ACTH responses compared with female subjects. Male subjects have also shown greater increases in epinephrine, blood pressure, and total peripheral resistance responses to performance tasks such as mirror star tracing, mental arithmetic, and public speaking Allen et al 1993, Girdler et al 1990, Matthews and Stoney 1988, Stoney et al 1987. In tests of basal HPA functioning, men have shown greater ACTH secretion compared with women, with no gender differences in cortisol secretion Dorn et al 1996, Horrocks et al 1990, Roelfsema et al 1993. Only in biological challenges to the HPA axis have women shown greater responses than men. Gallucci et al (1993) found that women exhibited greater and more prolonged ACTH responses to an ovine CRH (oCRH) challenge compared with men, with few gender differences in cortisol secretion; however, Dorn et al (1996) found a greater secretion of ACTH in male adolescents compared with their female counterparts following an oCRH challenge.
We hypothesized that most of the stressors in the human HPA stress studies have been achievement or instrumentally oriented (e.g., math problems, academic exams) and thus may have been more salient for male subjects. Instrumental traits tend to be more central to men’s self-construal than to women’s (e.g., Cross and Madson 1997), which might lead to greater investment in and physiologic responses to achievement-oriented tasks. This might explain the contrast between gender differences in human stress responses and gender differences in depression. In support of this, studies of gender role stress have shown that situations involving interpersonal concerns were perceived as more stressful for female subjects, whereas situations involving intellectual inferiority and performance failures were perceived as more stressful for male subjects Eisler and Skidmore 1987, Gillespie and Eisler 1992. Furthermore, Taylor et al (2000) proposed that women’s stress response may be better characterized by “tend and befriend,” involving nurturant activities and the creation of social networks, whereas men’s may involve the more traditional “fight or flight” response. Similarly, Cyranowski et al (2000) suggested that greater intensification in affiliative need along with exposure to negative events, particularly those with interpersonal consequences, may be one factor underlying the emergence of gender differences in depression during adolescence.
We propose that sex differences in HPA stress responses may be one mechanism underlying sex differences in depression. In particular, we predicted that women would show greater responses to social rejection stress, but men would demonstrate greater responses to achievement-oriented stress. To test this hypothesis, we examined sex differences in adrenocortical responses to achievement and social rejection stressors in healthy young male and female subjects.
Section snippets
Overview
First, a validation study verified the stressors as social rejection and achievement-oriented. For the main experiment, we randomly assigned men and women to the social rejection or the achievement challenge. Following a rest session to eliminate cortisol increases due to novelty, salivary cortisol was measured before, during, and after the stressors in a repeated-measures design.
Participants
Twenty-seven men and 31 women ranging in age from 17 to 23 years participated in the study. Exclusion criteria were
Baseline cortisol and affect measures by sex and stressor condition
To assess for unexpected baseline differences between conditions as well as baseline sex differences, we conducted a series of 2 (gender) × 2 (condition) ANOVAs comparing participants on year in college, baseline cortisol, and baseline NA and PA. No significant main effects for condition emerged, indicating that participants were appropriately randomized to experimental conditions. No significant sex differences in grade, or baseline NA, PA, or cortisol emerged.
There were no significant gender
Discussion
This experiment examined sex differences in HPA responses to social rejection and achievement stress in healthy subjects as a preliminary investigation into HPA stress responses as a mechanism underlying gender differences in depression. We tested the hypothesis that male subjects would show greater adrenocortical responses to an achievement challenge, but that female subjects would show greater responses to the rejection challenge. As predicted, with the effects of laboratory novelty
Acknowledgements
Preparation of this manuscript was supported in part by a NARSAD Junior Investigator Award to the first author. This work was also supported by NIH/NCRR/GCRC Program Grant No. RR00125 to the General Clinical Research Center at Yale; grants from the American Psychological Association, the Enders Research Foundation, and the Sigma Xi Scientific Research Society to the first author; and grants from the National Cancer Institute, National Institute of Mental Health, Mellon Foundation, and the
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