HPA Axis Reactivity in Depression: Relation of Childhood Maltreatment, Affect Lability, & Testosterone

Abstract

Stress is one of the most important etiological factors implicated in depression. A principle physiological stress response system is the hypothalamic-pituitary-adrenal (HPA) axis. Dysregulation of the HPA axis is proposed as a mechanism that may help translate stress exposures, such as childhood maltreatment (CM), into heightened risk for depression. Further, sex differences in HPA axis regulation have been proposed to help explain women’s heightened vulnerability to depression. Overall, depression and CM are associated with blunted HPA axis reactivity to stress. However, studies also show patterns of heightened HPA axis reactivity in relation to depression, including among depressed individuals with CM, suggesting that other vulnerability factors may be necessary to promote blunted reactivity in depression. Two factors associated with depression in women, and which interact with the HPA axis, are disturbances in affective processes, such as affect dynamics, and hypothalamic-pituitary-gonadal axis functioning. Thus, in the current dissertation, in two separate models, I examine whether the relation of depression and childhood maltreatment on HPA axis reactivity may be further moderated by two indices of these systems, namely affect lability and basal testosterone. Specifically, I assessed HPA axis reactivity by assessing salivary cortisol output in response to a laboratory stress task (Trier Social Stress Test) in a sample of depressed and non-depressed women (i.e., no lifetime history of psychopathology). Childhood maltreatment was assessed as the presence of severe CM (sCM) using a rigorous contextual interview, affect lability was assessed via self-report, and basal testosterone was assessed via blood serum. Although I found that the relation of depression and HPA axis reactivity was moderated by sCM, affect lability, and testosterone, the specific pattern of effects among depressed women were not as hypothesized. Instead, I found that affect lability and testosterone helped to further characterize HPA axis reactivity but only for depressed women with no sCM, such that low affect lability/testosterone was associated with lower cortisol reactivity. In contrast, depressed women with sCM showed disturbances in HPA axis responding in the acclimation period just prior to the TSST regardless of affect lability. Implications and future directions for understanding HPA axis functioning in depression are discussed.