The Influence of Estradiol on GABAergic Signaling in Perimenopausal-Onset Anhedonia 2026 Award: $59,326 Depression characterized by anhedonia—decreased interest or pleasure—during perimenopause is common, but our knowledge of how this arises and how to best treat it remains understudied. In this project, we will examine how hormonal variability and signals in the brain linked to mood respond to estradiol treatment. Findings will provide the first step towards development of novel treatments and inform the use of existing treatments to alleviate depressive symptoms during perimenopause. Need/Problem: Anhedonia, the loss of interest or pleasure, that arises during perimenopause is prevalent and associated with marked distress and reduced functioning. Improved understanding of the biological basis of perimenopausal-onset anhedonia and its treatment with estradiol is needed to shape intervention and alleviate suffering. Grant Summary:To examine a potential biomarker of perimenopausal-onset anhedonia, we will measure [...]

Establishing a UNC perinatal wearable data lake forpassive detection of postpartum depression 2026 Award: $58,820 Every year, millions of new mothers silently struggle with postpartum depression, not because help isn't available, but because the condition is never detected. Most women go undiagnosed. Our research aims to change that by turning the wearable device a woman already owns into an early warning system. Using AI to analyze patterns in heart rate, sleep, and activity data, we are developing a tool that can passively flag women who may be at risk, no clinic visit, no questionnaire, no extra burden required. This project will validate and expand that tool at UNC and build the data infrastructure needed to bring passive, technology-driven mental health screening into clinical practice.  Need/Problem: Postpartum depression affects about 1 in 6 new mothers, yet fewer than 1 in [...]

Suicide prevention among perinatal psychiatric inpatients: A randomized clinical trial 2025 Award: $59,999 Suicide is a leading cause of postpartum maternal deaths, yet no suicide prevention programs exist that are designed specifically for pregnant and postpartum women. This is a huge gap in maternal mental healthcare that we will address with this project. Thanks to the Foundation of Hope, we will be able to design and test the first ever perinatal-specific suicide prevention program for women who are experiencing high levels of psychological distress and suicide risk. Need/Problem: Suicide is a leading cause of postpartum maternal deaths in the United States, yet no perinatal suicide prevention programs exist. Some interventions indirectly reduce perinatal suicide risk by treating other mental health conditions, like postpartum depression, but these interventions are not always feasible for higher-risk patients who need more rapid, targeted [...]

Neurobiological mechanisms of susceptibility to estradiol fluctuation in female adolescents at risk of suicide: An experimental approach 2025 Award: $200,000 Female adolescents are 2-3 times more likely than their male peers to experience severe mental illness, possibly due to sensitivity to changing ovarian hormones (e.g., estradiol). Yet, the biological mechanisms that contribute to this elevated risk in females remain unclear. In this study, we will examine relationships between estradiol and depressive symptoms across the adolescent menstrual cycle to identify distinct windows of vulnerability to estradiol change, and use the experimental stabilization of estradiol to isolate the role of estradiol on depressive symptoms and underlying brain circuitry in female adolescents at risk of suicide. Need/Problem: Rates of suicidal ideation and attempts increase dramatically at the adolescent transition, particularly among females, yet remarkably little is known about why. With suicide being [...]

Examining the effect of estradiol on mood symptoms during perimenopause through immune gene expression 2024 Award: $44,745 Depression can increase during the transition to menopause (“perimenopause”), and hormonal treatments can help alleviate depressive symptoms. However, the mechanisms of how these treatments work and who they work for remain unclear. In this study, we propose the immune system may play a critical role in depressive symptoms and their treatment. Need/Problem: Rates of depression rise during the transition to menopause (“perimenopause”). Hormone treatments with estradiol can be helpful, but they are not effective or feasible for everyone. More research is needed to understand how and why estradiol works to better inform novel treatment approaches. Grant Summary: We will study expression of immune-related genes in a sample of perimenopausal women with depressive symptoms before and after three weeks of estradiol treatment or [...]

Increasing Access to Evidence-Based Therapy for Perinatal Women: A Novel App-Based Approach 2024 Award: $64,840 Perinatal depression affects 1.4M Americans each year and is a leading cause of maternal morbidity and mortality, yet only 7% of those with perinatal depression are diagnosed and treated effectively. Barriers to high-quality, evidence-based care are too high. We have created an new, internet-based behavior therapy app to overcome barriers to care, but we need to determine whether it works to treat depression and whether women find the app usable and relevant to their care. In this study, we will test the efficacy, acceptability, and feasibility of this new behavior therapy app. Identifying a population-level, cost-effective, evidence-based behavioral approach to treating perinatal depression would reduce the global burden of illness and improve the lives of women and their children. Need/Problem: Perinatal depression affects 1.4M [...]

Developing a pre-clinical model to study the interaction of female pubertal hormones and early-life stress in vulnerability to anhedonia 2024 Award: $44,577 This preclinical study aims to explore the interaction between chronic stress and reproductive hormones during puberty in females and investigating their role in vulnerability to depression in adulthood. Focusing on anhedonia, or the inability to experience pleasure, we will investigate the impact of these interactions on cortico-striatal circuits, offering insights into potential resilience factors and critical windows of vulnerability, thus advancing our understanding of major depressive disorder in women. Need/Problem: After puberty, women present twice the prevalence of major depressive disorder than men. The mechanisms by which reproductive hormones shape vulnerability to chronic stress-induced depression during puberty in women remain unexplored. Grant Summary: We will study how chronic stress interacts with reproductive hormones in females to shape [...]

Do APOE4+ women stand to benefit from menopausal hormone therapy? Piloting an experimental therapeutics approach to accelerate progress in dementia prevention research. 2023 Award: $44,875 Menopausal hormone replacement therapy (HRT) is not currently recommended to reduce risk for Alzheimer’s disease. However, emerging evidence suggests women who are APOE-4 carriers (the “Alzheimer’s gene”) may benefit from early initiation of HRT during the menopausal transition to reduce Alzheimer’s risk. We will pilot a short-term randomized, placebo-controlled trial to determine the potential efficacy of perimenopausal estrogen treatment to improve cognitive and brain markers associated with Alzheimer’s Disease in APOE-4 carriers compared to non-carriers. Need/Problem: Menopausal hormone replacement therapy (HRT) is not currently recommended to reduce risk for Alzheimer’s disease. However, emerging evidence suggests women who are APOE-4 carriers (the “Alzheimer’s gene”) may benefit from early initiation of HRT during the menopausal transition [...]

The Other Postpartum: Depression, Anxiety, and Post-Traumatic Stress Disorder following Stillbirth and Neonatal Death 2023 Award: $45,791 Each year, 1% of all live birth will be stillborn or result in neonatal death. The women and families that suffer these losses are at increased risk of anxiety, depression, and PTSD; however, their outcomes remain understudied, underrecognized, and undertreated. The grant allows us to begin to prospectively follow these women to begin to lay the groundwork for further investigation into biological risks, prevention, and best interventions. Need/Problem: Stillbirth and neonatal demise affects 1% of all live births. The repercussions of these losses have been understudied and undertreated, leaving many women and families to suffer without clear guidance and treatment options. Grant Summary: We will prospectively map the course depression, anxiety, and Post Traumatic Stress Disorder (PTSD) following stillbirth and neonatal loss and, for [...]

Mechanisms of Brexanolone Therapeutics in Post-Partum Depression: Expanded follow-up study 2023 Award: $100,000 Brexanolone is the first FDA approved medication for postpartum depression. This medication has a different mechanism of action than typical antidepressants and we will be investigating brexanolone’s impact on the systemic inflammatory pathways. Better understanding of why brexanolone is so effective for postpartum depression may provide a better understanding of postpartum depression itself and development of more accessible therapeutics. Need/Problem: Brexanolone is recently the first FDA approved medication for postpartum depression, which happens to be the most common complication of childbirth. This medication is an exciting development in psychiatry, in that it is rapidly acting, given by IV infusion over 60 hours, and has a vastly different mechanism of action than typical antidepressants. Despite these successes, there are limitations in that it requires a multiple day [...]