Cortisol reactivity following pharmacological “clamp” exposes women’s vulnerability to major depressive disorder

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2016-05

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Jin, Shuo

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Abstract

Stress-evoked hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis—typically measured via cortisol activity—is a major risk factor in the pathogenesis of major depressive disorder (MDD). However, the standard laboratory assessment of stress reactivity—the Trier Social Stress Test (TSST)—reveals no sex differences, despite the finding that women experience MDD at about twice the rate of men. One possibility is that HPA axis responses to the TSST are at or the near physiologic ceiling. If true, then down-regulation of the HPA axis prior to TSST administration might reveal the expected sex difference in HPA axis response. To this end, we hypothesized that suppression of HPA axis response using dexamethasone would reveal the sex difference in TSST-evoked cortisol reactivity, thus supporting the role of hypercortisolemia in the pathophysiology of MDD. Prior to TSST administration, 92 healthy, never-depressed participants (50% female) were randomized to receive either two placebo pills, or 2mg dexamethasone and 80mg propranolol. Cardiovascular (heart rate) and HPA axis (cortisol) responses were assessed before, during, and after TSST administration. Replicating previous work, analyses revealed no sex differences in cortisol reactivity in the placebo condition. However, as hypothesized, relative to men, women showed greater TSST-evoked HPA axis reactivity in the drug condition. This sex difference was not explained by sex differences in depression, anxiety, anxiety sensitivity, or history of adverse childhood experiences. By describing conditions under which sex differences in acute-stress hyperreactivity will emerge, the current study lends support to the role of stress-evoked hyperreactivity in the pathophysiology of MDD.

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