Estrogen, Stress, and Depression: Cognitive and Biological Interactions

Abstract

This article reviews the interactions of estrogen changes and psychosocial stress in contributing to vulnerability to major depressive disorder (MDD) in women. Estrogen modulates brain networks and processes related to changes in stress response, cognition, and emotional dysregulation that are core characteristics of MDD. Synergistic effects of estrogen on cognitive and emotional function, particularly during psychosocial stress, may underlie the association of ovarian hormone fluctuation and depression in women. We propose a model of estrogen effects on multiple brain systems that interface with stress-related emotional and cognitive processes implicated in MDD and discuss possible mechanisms through which reproductive events and changes in estrogen may contribute to MDD risk in women with other concurrent risk factors.

Keywords: attention; depression; emotion regulation; estrogen; steroids; stress.

Figure 1

Ventral and dorsal brain systems for emotion appraisal and regulation. Abbreviations: ACC, anterior cingulate cortex; PFC, prefrontal cortex.

Figure 2

Hypothalamic–pituitary–adrenal axis.

Figure 3

Ovarian hormones. (a) The hypothalamic–pituitary–gonadal axis in women. (b) Ovarian hormones during the menstrual cycle.

Figure 4

Proposed effect of differing estradiol levels during the menstrual cycle on dorsal and ventral emotion systems and interactions with stressful life events (e.g., trauma). (a) Low estradiol levels during the early follicular phase. (b) High estradiol levels during the periovulatory phase. The relative size of shapes indicates increased or reduced effects. High-estradiol-level phases during the menstrual cycle enhance the activity of dorsal regulatory structures during or following stressful events and lead to reduced activity of structures associated with negative emotions and better reappraisal, less negative emotional memory, and reduced negative affective state. This relationship changes during low estradiol phases. Abbreviations: ACC, anterior cingulate cortex; DL, dorsal lateral; DM, dorsal medial; OFC, orbital frontal cortex; PFC, prefrontal cortex; V, ventral; VL, ventral lateral. Figure adapted from Newhouse & Albert (2015).