Women’s Mood Disorders

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 [...]

Probing the neurophysiological mechanisms underlying sex-specific testosterone-mood relationships during puberty: A randomized controlled trial using a smartphone-based training program 2023 Award: $45,080 Female and male adolescents may respond differently to pubertal changes in testosterone. This study will examine whether brain activity associated with emotion regulation may link testosterone change with different symptom profiles. Further, we will test the effects of a smartphone-based training program on brain dynamics underlying emotion regulation and symptoms of depression – the first step in developing new intervention and treatment approaches for adolescent psychopathology. Need/Problem: The pubertal transition marks an abrupt divergence between the sexes in rates of depression and other internalizing disorders in female adolescents, and externalizing disorders (i.e., attention-deficit/hyperactivity disorder (ADHD)) in male adolescents. The COVID-19 pandemic has further widened the gender gap in adolescent mental health, with a concerning escalation in depression, [...]

Hormone Flux and the Emergence of Irritability During Pregnancy: Investigating the Trajectory and Neurobiological Correlates of an Underrecognized Mood State2022 Award: $40,000Irritability is common in perinatal depression, however we do not know when irritability emerges during pregnancy and the neurobiological pathways underlying symptom progression are poorly understood. In this study we will investigate how hormone changes across pregnancy relate to the onset of irritability in women at risk for perinatal depression. We will also evaluate how hormone changes relate to neural and behavioral responses to threat and frustration, key components of irritability. Investigating the emergence and neurobiological correlates of irritability in perinatal depression is a critical first step to shed led light on this often underrecognized mood state and identify potential targets for prevention and intervention efforts that support the wellbeing of women and children.Need/Problem: Irritability is common in reproductive [...]

Monitoring Affective State Change with Wearable Technology: Assessing Physiological and Behavioral Mechanisms in Premenstrual Dysphoric Disorder 2021 Award: $40,000 Real-time monitoring during the transition in to or out of depression (affective state change) is an important precursor to providing targeted interventions to reduce high-risk periods of suicide and early detection and treatment for depression relapse. In this project, we capitalize on widely used wearable technology that can passively collect such real-time data including variables known to be associated with affective state change. Premenstrual dysphoric disorder (PMDD) provides a depression model with monthly switching of affective state. Establishing the physiological variables related to mood transition in PMDD is a first critical step in identifying mechanisms of risk for depression and suicide to develop a prediction model that may be applied to other mental health conditions. Need/Problem: Depression rates are continuing [...]

The Comorbidity of Depression and Cardiovascular Disease in Midlife Women: Investigating novel biological pathways of risk 2021 Award: $39,617 The risk for developing depression and cardiovascular disease increases significantly in midlife women and this combination of illnesses is a leading cause of disability in this population.  Disruption in the physiological pathways involved in stress response may underlie the connection between these illnesses, though this has not been fully studied. The primary objective of this proposal is to examine whether dysfunction in the renin-angiotensin-aldosterone system and autonomic nervous system pathways may be a mechanistic link underlying the association between depression and cardiovascular disease in women. Need/Problem: Depression and cardiovascular disease (CVD) contribute significantly to the morbidity and mortality of women. About 20% of women are impacted by this comorbidity, which is also the leading cause of disability in women worldwide. The [...]