The proposed project will address the nature and impact of anxiety in women by examining the interplay of anxiety, cognitive control dysfunction, and ovarian hormones (i.e., estradiol and progesterone). Despite sex differences in brain structure and function critical to cognitive control, limited works has been dedicated to directly examining how such differences might play a role in how anxiety manifests in and affects women. We will address this glaring gap in our understanding of anxiety in women by testing the novel hypothesis that estradiol amplifies the association between anxiety - verbal worry, in particular - and cognitive control dysfunction. The design of the study uses a community sample of young adult females assessed intensively across the menstrual cycle to directly examine the contributions of ovarian hormones to the association between worry and cognitive control dysfunction. It will leverage the power of an interdisciplinary collaborative team consisting of experts in cognitive neuroscience, neuroendocrinology, women's health, clinical psychology, and computer engineering. The proposed project will involve collecting daily measures of anxiety-related symptoms and ovarian hormones as well as neurobehavioral indices of cognitive control at four separate occasions during the menstrual cycle.
The specific aims of the study are to: 1) establish the role of estradiol in the association between worry and impaired working memory, 2) confirm the role of estradiol in the association between worry and maladaptive cognitive control-related performance monitoring, and 3) delineate the role of estradiol in the interactive effect of worry and working memory on maladaptive cognitive control-related performance monitoring. The long-term promise of this research is that it will elucidate a neuroendocrinological mechanism involved in the unique nature and impact of anxiety in women. Our multi- method, mechanistic approach has the potential to pinpoint particular periods of elevated risk for anxiety- related cognitive dysfunction during the menstrual cycle and across the lifespan (e.g., puberty), as well as identify novel neurobiological treatment targets for anxiey disorders in women.

Public Health Relevance

Women are nearly twice as likely to suffer from an anxiety disorder than men and suffer greater disability related to anxiety such as having more than one mental health problem, missing more days of work and making greater use of health care. The proposed research applies an integrative approach involving the measurement of cognitive dysfunction, ovarian hormones, and anxiety symptoms in young adult females. This will enable us to test whether female hormones play a role in how brain activity used to correct mistakes and control behavior is affected by anxiety in women so that better diagnostic tools and treatment techniques can be developed that take female-specific factors into account.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Prabhakar, Janani
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Michigan State University
Schools of Arts and Sciences
East Lansing
United States
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