Depression is the leading cause of disability and a major contributor to the overall global burden of disease.1 As the 2022 Lancet Commission for Depression highlights, despite how common depression is across the life course, critical barriers have prevented depression from receiving sufficient resources and global attention.1 Depression has historically been stigmatized and misunderstood, and it arises due to a combination of biological, social, and psychological factors. Limited access to treatment and lack of cross-disciplinary, collaborative research and care has hindered progress. Additionally, women are disproportionately affected by depression and are twice as likely to have a diagnosis of depression as men, likely due to the combination of health inequities, gender biases, and biological factors.1 Depression is also a risk factor to develop dementia when elderly, and it might be a reason more women have dementia than men.2 Developing innovative solutions for depression—especially those focused on women that account for sex and gender differences—are critical to improving individual and collective resilience.
To develop women-focused solutions for depression, it is important to understand the various factors that contribute to women’s greater risk for depression. A health equity and public health lens is imperative. The distinction between sex and gender also needs to be clear, with sex referring to biological differences and gender encompassing socially constructed and enacted roles and behaviors shaped by historical and cultural contexts. Additionally, diagnostic tools, symptom screeners, medications, and other health tools must not have sex or gender bias.
Women in their reproductive years undergo cycle changes in steroid hormones (progesterone/estrogen) over the menstrual cycle. The role of these changes as a factor contributing to depression and mood changes is seen in women with premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). The estimated prevalence in reproductive women is 5% (PMDD) and 20% (PMS). There is growing evidence that the rise in ovarian steroid hormone production and the effect of their metabolites (in particular allopregnanolone) on central brain receptors as progesterone receptor modulators contribute to the mood symptoms in PMDD and PMS.3 More research is needed to understand the long-term neurological impacts of birth control and hormone therapy.4 Treatments are now being developed to target these newer proposed actions of hormones on the central brain systems with either suppressing ovarian function (removing the natural fluctuations in hormones) or “correcting” the neurotransmitter or neurosteroid dysregulation with the use oftargeted specific antidepressants.5,6
The female preponderance in depression occurs largely during the reproductive years, is not evident before puberty, and is less marked after menopause. Societal factors may also play an important role; even in developed countries, women still often take a greater responsibility for child rearing and domestic activities while still being expected to progress their careers—known as a “double day.” Women worldwide are also the majority of caregivers for family members needing health care; often this role is unpaid.
Intimate Partner Violence
Depression is also linked to intimate partner violence (IPV). One in 3 women globally have experienced physical or sexual IPV.7 Since the outbreak of COVID-19, IPV has escalated and been called the shadow pandemic of COVID-19. In numerous countries, there has been a 300% increase in police reports of IPV, likely fueled by effects and mitigation strategies of COVID-19.8 UN Women projected that an additional 15 million women would be affected by IPV for every 3 months of lockdown.9
One particularly devastating yet unaddressed and long neglected impact is the mental and brain health effects—including traumatic brain injury (TBI) and depression—resulting from IPV. Numerous studies have found that women exposed to IPV are more likely to develop depression than women who are not exposed.10 This finding is not surprising, given that mental health issues are common sequelae of brain injury that may emerge and worsen years after injury. However, IPV is too often left out of conversations around prevention and treatment of depression.
Chronic Health Conditions
It is also important to note the connection between depression and chronic health conditions in women, such as heart disease. Since 1989, heart disease has been the leading cause of death in US women.11 Women are also more likely than men to die after a heart attack.11 Women are more likely to be undiagnosed, misdiagnosed, or poorly treated for their heart disease due to pervasive bias and the male body being the default for biomedical care and research. Additionally, the Guidelines for the Prevention of Cardiovascular Disease in Women by the American Heart Association show the profound impact of hypertension, diabetes, and depression on women’s hearts.12 It is imperative to understand the huge impact of psychosocial risk factors on women’s hearts and address problems including depression and social isolation.12
Understanding the role of depression in dementia for women is also imperative. The WHAM Report (Women’s Health Access Matters) found that women are 66% of the nearly 7 million people in the United States with Alzheimer disease, and yet just 12% of 2019 NIH Alzheimer disease fund went to projects focused on women.13 Even more, the report showed the following: (1) Doubling the funds for women’s Alzheimer disease research pays for itself 3 times over; (2) this 224% return on investment adds 15% more to our economy than general Alzheimer disease research; and (3) adding $300 million for research on women generates $930 million in economic gains, adds back 4000 years of life, eliminates 6500 Alzheimer disease and related dementias, and saves 3500 years of nursing home care and costs. Depression is one of the largest modifiable risk factors for dementia.14 Thus, understanding the link between depression and dementia and accounting for depression in dementia prevention strategies in women is essential.14
Novel, women-focused solutions can reduce the impact of depression and increase global resilience. As a recent Rock Health report finds, women’s health solutions often remain siloed to pregnancy and reproductive-related issues.15 There is a dearth of women-focused solutions for chronic health and behavioral health and an even larger gap for solutions at the intersection of both.15 Women-focused solutions that include technology, drug development, and devices are urgently needed. Additionally, convergence solutions that combine multiple domains and technologies, such as blending platform and frontier technologies, are key.
Developing women-focused solutions is not only a medical and moral imperative—there is also significant economic and commercial upside. Emergen Research projects that the global market for women’s health will reach $60 billion in 2027.16 Additionally, women are the chief medical officers of society, controlling 80% of health care decisions in the United States and spending 29% more per capita on health care compared to men.17,18
By developing women-focused solutions for depression that account for various factors, including the relationship between depression with heart disease and dementia in women, we can build a more resilient society and world.
Ms Smith is an Atlantic Fellow for Equity in Brain Health at Global Brain Health Institute, a Thiel Fellow at Stanford University, and a Steering Committee member for OECD-PRODEO Institute Neuroscience-inspired Policy Initiative.Mr Heinemeyer is CEO of PRODEO and cofounder of the PRODEO Institute. Dr Chapman is founder and chief director of the Center for BrainHealth at UT Dallas. She is a distinguished professor at UT Dallas. Dr Zarutskie is a reproductive endocrinologist at Baylor College of Medicine. He is an active member of the American Society of Reproductive Medicine and the North American Menopause Society, with a special interest in the role of steroid hormones on cognitive function. Dr Wainer is deputy secretary of public health in the Victorian Department of Health and Honorary Melbourne Enterprise Professor with the University of Melbourne. Dr Berk is a NHMRC senior principal research fellow, Alfred Deakin professor of psychiatry at Deakin University, and director of the Institute for Mental and Physical Health and Clinical Translation at Deakin University. Dr Chadha is CEO and cofounder of the Women’s Brain Project. Dr Eyre is colead of the OECD-PRODEO Institute NIPI.He is a senior fellow in brain capital for the Meadows Mental Health Policy Institute. He holds adjunct or advisory roles with IMPACT at Deakin University, the Heka Fund, Brain Health Nexus at Cohen Veterans Bioscience, GBHI, Baylor College of Medicine, Latin American Brain Health (BrainLat), Universidad Adolfo Ibáñez, Chile, University of Texas Health Sciences Center at Houston, the Davos Alzheimer’s Collaborative and the Euro-Mediterranean Economists Association.
1. Herrman H, Patel V, Kieling C, et al. Time for united action on depression: a Lancet-World Psychiatric Association Commission. Lancet. 2022;399(10328):957-1022.
2. Barnes DE, Yaffe K, Byers AL, et al. Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch Gen Psychiatry. 2012;69(5):493-498.
3. Lanza di Scalea T, Pearlstein T. Premenstrual dysphoric disorder. Med Clin North Am. 2019;103(4):613-628.
4. Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study. BMJ. 2019;364:l665.
5. Schmidt PJ, Martinez PE, Nieman LK, et al. Premenstrual dysphoric disorder symptoms following ovarian suppression: triggered by change in ovarian steroid levels but not continuous stable levels. Am J Psychiatry. 2017;174(10):980-989.
6. Hantsoo L, Grillon C, Sammel M, et al. Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder. Psychopharmacology (Berl). 2021;238(10):2985-2997.
7. Breiding MJ, Smith SG, Basile KC, et al. Prevalence and characteristics of sexual violence, stalking, and intimate partner violence victimization–national intimate partner and sexual violence survey, United States, 2011. MMWR Surveill Summ. 2014;63(8):1-18.
8. Valera EM. When pandemics clash: gendered violence-related traumatic brain injuries in women since COVID-19. EClinicalMedicine. 2020;24:100423.
9. Mlambo-Ngcuka P. Gender-based violence: we must flatten the curve of this shadow pandemic. November 25, 2020. Accessed May 12, 2022. https://www.un.org/africarenewal/magazine/november-december-2020/gender-based-violence-we-must-flatten-curve-shadow-pandemic
10. Ellsberg M, Jansen HAFM, Heise L, et al. Intimate partner violence and women’s physical and mental health in the WHO multi-country study on women’s health and domestic violence: an observational study. Lancet. 2008;371(9619):1165-1172.
11. Mehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation. 2016;133(9):916-947.
12. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association. J Am Coll Cardiol. 2011;57(12):1404-1423.
13. Baird MD, Zaber MA, Dick AW, et al. Societal Impact of Research Funding for Women’s Health in Alzheimer’s Disease and Related Dementias. Rand Corporation; 2021.
14. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413-446.
15. DeSilva J, Krasniansky A. Building comprehensive women+ digital health: Eight sectors serving women+ needs. Rock Health. September 27, 2021. Accessed May 12, 2022. https://rockhealth.com/insights/building-comprehensive-women-digital-health-eight-sectors-serving-women-needs/
16. Femtech Market By Type (Devices, Software, Services), By End-Use (Direct-to-Consumer, Hospitals, Fertility Clinics, Surgical Centers, Diagnostic Centers), By Application (Reproductive Health, Pregnancy & Nursing Care, Pelvic & Uterine Healthcare), By Region, Forecasts to 2027. EMERGEN Research. June 2021. Accessed May 12, 2022. https://www.emergenresearch.com/industry-report/femtech-market
17. Femtech—time for a digital revolution in the women’s health market. Frost & Sullivan. January 31, 2018. Accessed May 12, 2022. https://www.frost.com/frost-perspectives/femtechtime-digital-revolution-womens-health-market/
18. Gambon E, Stotz C, Sandhu N. Femtech is expansive—it’s time to start treating it as such. Rock Health. August 3, 2020. Accessed May 12, 2022. https://rockhealth.com/femtech-is-expansive-its-time-to-start-treating-it-as-such/