Women’s Mood Disorders

Depression in the menopause transition: cortisol circadian rhythms and sleep impairment as mechanisms of risk Award: $38,400 The menopause transition (MT) is a vitally important, yet understudied, period of time in women’s health. Women in the MT experience significant hormonal changes (e.g., estrogen), are at a 2-4-fold increased risk for developing significant depressive symptoms, and report substantial changes in sleep health. In this project, we will examine the role of hormone variability on sleep impairment as a potential mechanism for the development of depression. Need/Problem: The menopause transition (MT) is a critical time period in women’s health, characterized by changes in reproductive hormones (changes in estrogen), a 2-4-fold increase risk for major depression (MDD), and the emergence of significant sleep impairment. To date, experimentally controlled sleep science research in women’s health is scant. Grant Summary: This research utilizes a [...]

The gut microbiome and Perinatal Mood and Anxiety Disorders (PMAD): A pilot study to examine the microbiome in relation to perinatal changes in stress and immune systems Need/Problem: PMAD are common and can have grave consequences for mother including a risk of suicide and negative effects on the child’s development. However, the biologic mechanisms underlying PMAD are unclear. There is evidence that certain gut microbiota are associated with depression and anxious behaviors. Grant Summary: This grant is a novel approach to studying PMAD by studying the microbiota of women across the perinatal period (pregnancy and the postpartum time period) in relation to the development of depression and anxiety. Goals and Projected Outcomes: The goal of the study is to collect and analyze the gut microbiota samples in each trimester and 8 weeks postpartum from women with histories of mood [...]

Genomics of Postpartum Depression–Action towards Causes and Treatment (gPACT); PACT for the Cure Need/Problem: Postpartum depression (PPD) and postpartum psychosis (PPP) affect millions of women worldwide and are the leading cause of maternal morbidity and mortality. Research on the causes of PPD and PPP are greatly underfunded leaving researchers and clinicians with an incomplete understanding of who is at risk. Grant Summary: This project is an innovative and novel approach to rapidly elucidate the genetic basis of PPD and PPP by conducting an extremely rapid and large genome-wide association study. This will improve detection, prevention and treatment of these conditions. Goals and Projected Outcomes: Our goal is to learn more about the biological basis of PPD and PPP by conducting a large genome-wide association study using Apple’s newly created open-source Research Kit software. We anticipate enrolling 100,000 women in [...]

Single cell transcriptional profiling to identify novel neurocircuit targets for reproductive mood disorders Need/Problem: There are few rational strategies for targeting neuronal cell types in the brain for the treatment of neuropsychiatric disease. We propose to utilize state of the art high throughput sequencing technology establish an experimental and computational pipeline to quantitatively assess the number of cell types on the mammalian hypothalamus and how these are regulated by various reproductive hormonal manipulations. Grant Summary: This grant proposes experiments to classify the number of phenotype of neurons in the mammalian brain. Goals and Projected Outcomes: The goal of the study is to develop a high-throughput experimental and computational pipeline for accurately classifying and describing neuronal cell gene expression changes in response to environmental or hormonal manipulations. This approach will identify many novel therapeutic targets for the treatment of neuropsychiatric [...]

Characterizing the Hormone Sensitive Phenotype of Postpartum Depression: An Experimental Investigation of Mood and Behavior Need/Problem: Despite decades of research, little is known about the biological causes of postpartum depression. Our past research showed that changes in pregnancy hormone levels cause depression in some women, but at present, there is no simple way to identify these women. Grant Summary: This research provides a novel approach to testing risk for postpartum depression. Goals and Projected Outcomes: The purpose of this project is to test two simple, non-invasive approaches to identifying women at high-risk for postpartum depression. The projected outcome of this project is the ability to distinguish those at high and low risk for postpartum depression using minimally invasive, easy-to-implement protocols, thus potentially enabling the identification of women at risk for postpartum depression prior to its development. Crystal [...]

Depression Susceptibility in Adolescent Females: Estrogen Variability, Stress Exposure, and Fronto-Limbic Brain Dynamics Need/Problem: Dramatic fluctuations in reproductive hormones (e.g., estrogen), refinement of brain circuitry involved in cognitive and emotional processing, and elevated psychosocial stress during the pubertal transition (peripuberty) accompany a substantially increased risk for depression, particularly for adolescent girls. Although normal changes in estrogen provoke affective symptoms in vulnerable women during reproductive events, the role of changing estrogen levels in depression risk has not been studied in peripubertal girls. Furthermore, the neurophysiologic mechanisms underlying the vulnerability to estrogen fluctuations have yet to be identified. Grant Summary: : Estrogen exerts significant modulatory effects on the cortisol stress response and brain circuitry involved in regulating affective (mood) state. With the Foundation of Hope’s support, this research will use a novel multimodal approach involving precise ovarian hormone measurements, neurophysiological assessments of [...]

gPACT – a rapid large & inexpensive study of Postpartum Depression Award: $99,000 Dr. Samantha Meltzer-Brody helped assemble an international team of researchers and clinicians who, using open-source Apple software, could gather information from thousands of women experiencing symptoms of postpartum depression (PPD). Selected participants would submit DNA samples for researchers to compare against DNA from women who have never experienced depression. With this study, Dr. Meltzer-Brody and her team hope to discover genetic factors that could lead to better prediction, diagnosis, and treatment for perinatal mental illnesses. Samantha Meltzer-Brody, M.D. Need/Problem:  Despite its prevalence—up to 1 in 7 mothers experience postpartum depression—and its devastating effects on women and their families, PPD (and, by extension, PPP) is a poorly understood condition. Grant Summary: In an effort to combat this issue, Dr. Samantha [...]