Estrogen, Stress, and Depression: Cognitive and Biological Interactions

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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.

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Most cited references 98

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Cognition and depression: current status and future directions.

Ian Gotlib, Jutta Joormann (2010)

Cognitive theories of depression posit that people's thoughts, inferences, attitudes, and interpretations, and the way in which they attend to and recall information, can increase their risk for depression. Three mechanisms have been implicated in the relation between biased cognitive processing and the dysregulation of emotion in depression: inhibitory processes and deficits in working memory, ruminative responses to negative mood states and negative life events, and the inability to use positive and rewarding stimuli to regulate negative mood. In this review, we present a contemporary characterization of depressive cognition and discuss how different cognitive processes are related not only to each other, but also to emotion dysregulation, the hallmark feature of depression. We conclude that depression is characterized by increased elaboration of negative information, by difficulties disengaging from negative material, and by deficits in cognitive control when processing negative information. We discuss treatment implications of these conclusions and argue that the study of cognitive aspects of depression must be broadened by investigating neural and genetic factors that are related to cognitive dysfunction in this disorder. Such integrative investigations should help us gain a more comprehensive understanding of how cognitive and biological factors interact to affect the onset, maintenance, and course of depression.

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Adult hippocampal neurogenesis buffers stress responses and depressive behavior

Jason Snyder, Amélie Soumier, Michelle Brewer … (2011)

Summary Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness 1, 2 . In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis 3 . Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking 4, 5 . Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioral components of the stress response. Using transgenic and radiation methods to specifically inhibit adult neurogenesis, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice compared with intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis 6, 7 . Relative to controls, neurogenesis-deficient mice showed increased food avoidance in a novel environment after acute stress, increased behavioral despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.

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Epidemiology of women and depression.

R Kessler (2003)

Depression is the leading cause of disease-related disability among women in the world today. Depression is much more common among women than men, with female/male risk ratios roughly 2:1. Recent epidemiological research is reviewed. Implications are suggested for needed future research. The higher prevalence of depression among women than men is due to higher risk of first onset, not to differential persistence or recurrence. Although the gender difference first emerges in puberty, other experiences related to changes in sex hormones (pregnancy, menopause, use of oral contraceptives, and use of hormone replacement therapy) do not significantly influence major depression. These observations suggest that the key to understanding the higher rates of depression among women than men lies in an investigation of the joint effects of biological vulnerabilities and environmental provoking experiences. Advancing understanding of female depression will require future epidemiologic research to focus on first onsets and to follow incident cohorts of young people through the pubertal transition into young adulthood with fine-grained measures of both sex hormones and gender-related environmental experiences. Experimental interventions aimed at primary prevention by jointly manipulating putative biological and environmental risk factors will likely be needed to adjudicate between contending causal hypotheses regarding the separate and joint effects of interrelated risk factors.

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Author and article information

Journal

Title: Annual Review of Clinical Psychology

Abbreviated Title: Annu. Rev. Clin. Psychol.

Publisher: Annual Reviews

ISSN (Print): 1548-5943

ISSN (Electronic): 1548-5951

Publication date Created: May 07 2019

Publication date (Print): May 07 2019

Volume: 15

Issue: 1

Pages: 399-423

Affiliations

[1 ]Center for Cognitive Medicine, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA;

[2 ]Geriatric Research, Education, and Clinical Center, Tennessee Valley Veterans Affairs Medical Center, Nashville, Tennessee 37212, USA

Article

DOI: 10.1146/annurev-clinpsy-050718-095557

PubMed ID: 30786242

SO-VID: f805a3d3-1ee3-482b-8f24-6383f9bcd0e4

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ScienceOpen disciplines: Sociology,Psychology,Anthropology,Social & Behavioral Sciences,General social science,General behavioral science

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ScienceOpen disciplines: Sociology, Psychology, Anthropology, Social & Behavioral Sciences, General social science, General behavioral science

Estrogen, Stress, and Depression: Cognitive and Biological Interactions

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Abstract

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Annual Reviews Child Development

Most cited references 98

Cognition and depression: current status and future directions.

Adult hippocampal neurogenesis buffers stress responses and depressive behavior

Epidemiology of women and depression.

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Journal

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