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Neuroscience and Psychiatry
July 2015

Estrogen, Stress, and DepressionA Neurocognitive Model

Author Affiliations
  • 1Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2Geriatric Research, Education, and Clinical Center, Veterans Affairs Tennessee Valley Health System, Nashville
  • 3Neuroscience Graduate Program, University of Vermont, Burlington
JAMA Psychiatry. 2015;72(7):727-729. doi:10.1001/jamapsychiatry.2015.0487

Increased vulnerability for depression in women begins with puberty and declines after menopause. Studies have shown that perimenopause produces increased vulnerability for depressive symptoms and new-onset depression even among women with no history of affective disorders. While the reason or reasons for vulnerability to such disorders in women remain to be fully understood, the strongest candidate is the influence of cycling levels of gonadal steroids, particularly estradiol (the predominant circulating estrogen), on neurotransmitter systems and mood regulatory systems, interacting with biological vulnerability and life stress. Alterations in how the brain conducts emotional processing and encodes and retrieves emotional information may be critical to sex and age differences in the incidence, prevalence, and treatment of emotional and cognitive disorders. The menopause transition is a neurobiological and endocrine event that has effects on a variety of tissue and organ systems; alterations in mood regulation during this stage may inform our understanding of sex hormone effects on emotional cognition.

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