Catherine Monk - US grants

DESCRIPTION (provided by applicant): Historically, an unsubstantiated view held that pregnancy was a protective factor against depression. Data now dramatically contradict this view. Approximately 10-15% of pregnant women are depressed, which puts them -- and their children ---at risk for the deleterious affects of postpartum depression. Moreover, new data indicate that prenatal depression also may adversely affect the child even before birth. Despite the high prevalence rates of prenatal depression and its negative consequences, few controlled studies have tested the efficacy of psychotherapy during pregnancy. None has examined the effects of successfully treated depression on the fetus and newborn. The goal of this application -- submitted under the NIMH R34 mechanism for exploratory intervention research -- is to determine if an intervention for prenatal depression can enhance women's pre- and postpartum moods and improve fetal and newborn functioning. Specifically, in a study of 80 depressed women randomly assigned to either of two treatment options and 40 psychiatrically-healthy pregnant women, we hypothesize that depressed pregnant women treated with a group version of Interpersonal Psychotherapy versus standard psychiatric care will result in: (a) improved prenatal mood, (b) less postpartum depression and (c) fetal and newborn neurobehavioral profiles similar to healthy women's offspring. In past work we have shown that fetuses of depressed women have altered heart rate responses suggestive of risk for future stress-based psychopathology. Women's mood will be assessed using standard rating scales. Fetal heart rate and movement will be assessed while women undergo a laboratory stressor. Newborn heart rate will be assessed during an orthostatic challenge. This study has the potential to alter the clinical approach to perinatal mood disorders by demonstrating that we can (1) prevent postpartum depression before it occurs and (2) positively influence the child's development by limiting their exposure to women's pre- and postpartum depression.

On any given day in the United States, more than 1100 adolescents give birth, and massive evidence demonstrates that their children are at increased risk for adverse perintal outcomes and future psychopalhology. New dala for 2006 indicale that the birth rate for U.S. adolescents ages 15-19 years old increased by 3% since 2005, the first increase since 1991 [1]. The population of adolescent girls is expected to grow by 10% by 2010 (2]. further increasing the number of births to teens. Adolescents who are pregnant are more often materially poor, and minorities, and this trend too is on the rise. Rates are 63.7 births per 1,000 for non-Hispanic black adolescents - a 5% increase from 2005;83.0 for Hispanic teenagers, a 2% increase, and 26.6 for non- Hispanic white adolescents, a 3% increase [1). The overall goal of this application is to determine if, in this underserved and understudied population, exposure to maternal antenatal stress contributes to poor birth outcomes and alterations in perinatal neurobehavioral development. Positive findings would indicate that risk for poor developmental trajectories is initiated in the perinatal period, and would suggest openings for preemptive psychosocial interventions. The specific goals of the biopsychosocial research proposed here are to (1) assess life stress in pregnant adolescents and relate it to offspring outcomes and (2) determine the biological pathways for this putative association using ecologically valid approaches.

DESCRIPTION (provided by applicant): Of the over 4 million live births each year in the United States, nearly 800,000 - or 20% - of the mothers will develop major or minor depression within the first 3 months postpartum. This number dwarfs prevalence rates for gestational diabetes (2-5%) and preterm birth (12.7%). Existing clinical approaches to postpartum depression (PPD) use standard pharmacologic and psychological interventions to reduce women's symptoms. Nevertheless, PPD is undertreated, in part because women are reluctant to seek treatment due to stigma associated with mental health care and disinclination to take psychotropic medications when breastfeeding. The consequences of this are substantial. Untreated PPD is associated with diminished quality of life and significant emotional suffering for women, and, through compromised caregiving, poor outcomes in children's cognitive and social-emotional development. Although maternal risk factors for PPD are well known, protocols for prevention based on commonly used depression interventions are only beginning to be evaluated. Building on developmental data showing the profound bi-directionality of emotional and behavioral influences between mother and infant, we propose testing a novel PPD intervention protocol that challenges the standard, individually-focused treatment paradigm. Our intervention is based on the conceptualization of PPD as a potential disorder of the dyad, and one that can be approached through behavioral change in and affective engagement with mother and child. Studies show that infant cry/fuss and sleep behavior are associated with PPD, and that parenting interventions can change infant behavior, yet these findings have never been applied to PPD. In this R21 application, we aim to collect pilot and feasibility data on a novel PPD risk-reducing protocol based on a dyadic behavioral approach to PPD in which we treat at-risk women by promoting maternally-mediated behavioral changes in their infants. We will select a sample of pregnant women at risk for PPD, teach parenting skills to increase infant nocturnal sleep and reduce fuss/cry behavior to half of the sample during 3 perinatal visits, then evaluate infant behavior at 6 and 14 weeks, and maternal mood at 6, 10, and 14 weeks postpartum. In line with NIMH's strategic goal to develop an integrative understanding of basic brain-behavior processes, we will fully exploit the investigative opportunities of this intervention study by using state-of-the-art EEG and fetal monitoring to characterize early biomarkers associated with infant behavior and behavior change. Our proposal has the potential to have a major impact on clinical research, and to transform the standard care of PPD in that (1) the intervention will have high rates of treatment compliance because (a) the protocol sessions can be incorporated into usual perinatal medical visits, (b) parenting skills will appeal to women as a non-psychiatric intervention, (c) the clinical approach will have face validity given the dyadic focus of the perinatal period; (2) its aim is prevention; (3) it fosters both maternal and child well being; (4) it will expand the risk factors for PPD to include neurobehavioral markers in the perinate. PUBLIC HEALTH RELEVANCE: Postpartum depression (PPD) is undertreated and the consequences of this are substantial for women and children. Studies show that infant cry/fuss and sleep behavior are associated with PPD, and that parenting interventions can change infant behavior, yet these findings have never been applied to PPD. We propose teaching parenting skills to increase infant nocturnal sleep and reduce fuss/cry behavior to women likely to develop PPD to see if we can prevent the onset of this disorder.

DESCRIPTION (provided by applicant): Nearly half of the U.S. population will meet criteria for a psychiatric disorder during their lives, and 1 in 17 has a seriously debilitating illness. Increasingly, these psychopathologies are conceptualized as the late-stage cul- mination of aberrant developmental processes shaped by a complex interplay of genes and experience, includ- ing those occurring in utero. Decades of studies with pregnant animals demonstrate that stress-elicited pertur- bations in maternal biology affect offspring development, leading to a profile characterized by heightened be- havioral and physiologic stress responsivity. Studies of distress in pregnant women, which range from exami- nations of life stress to psychiatric disorder, largely mirror these findings. Despite ample evidence linking ante- natal maternal functioning to offspring outcomes, the mechanistic pathways for this in utero influence on chil- dren's neurodevelopment remain unknown, particularly with human subjects. The burgeoning field of epigenet- ics - the detection of the molecular effects of environmental experience - has only minimally been applied to pregnant women, yet may provide a vital link in understanding the mechanisms involved in the fetal origins of psychiatric disease risk. The goal of this project is to use recent advances in studying epigenetic gene regulation to identify the biological mechanisms mediating the impact of maternal distress on perinatal development. Aim 1: Determine the influence of pregnant women's distress on epigenetic gene regula- tion relevant to perinatal development. Specifically, to establish whether (a) prenatal distress (daily life stress assessed 3x in pregnancy using 24-hour Ecological Momentary Assessment (EMA) via a Personal Digi- tal Assistant (PDA)) and mood symptoms elicited by clinician interviews) predict women's stress hormone lev- els (cortisol (from 3x, 12 salivary samples in 48-hours) and CRH (3x blood draws) and gene expression in her PBL (3x blood draws); (b) the timing and degree of women's altered stress hormone levels and PBL gene ex- pression predict placental gene expression; (c) these mood-dependent biological alterations are associated with the epigenetic mechanism of DNA methylation. Aim 2: Determine perinatal consequences of pregnant women's distress. Specifically whether, (a) women's distress-associated altered HPA-axis hormone levels, PBL and placental gene expression/epigenetic variation, predict fetal cord blood gene expression/epigenetic variation, as well as a neurobehavioral profile characterized by heightened reactivity to novelty (fetal and new- born autonomic and central nervous system regulation in response to stimuli). Aim 3: Establish causal influ- ence of epigenetic modification on offspring neurodevelopment. Specifically, using a rodent model in which brain effects of chronic maternal prenatal stress exposure can be directly assessed, we aim to determine (a) the influence of maternal condition on DNA methylation and gene expression in maternal PBLs, placenta, and in the fetal/infant brain and, (b), the relationship between epigenetic variations in these tissues and the de- velopment of the postnatal ANS and CNS as indexed by behavioral and stress-hormone responsivity.

DESCRIPTION (provided by applicant): Children's neurocognitive development can cast long shadows on their futures, dramatically influencing their occupational functioning and psychosocial adjustment. While it is increasingly recognized that normative variation in early environmental experiences (i.e. parenting style), plays a significant role in shaping cognitive development, evidence indicates that the impact of the environment on cognitive development begins in utero. Two common experiences during pregnancy, psychosocial stress and inadequate micronutrient intake - prominently, iron and zinc, affect outcomes. Prenatal anxiety predicts delayed mental and motor development on the Bayley Scales in infancy, and a reduction in gray matter in the middle temporal lobe based on brain imaging in school-age children. Animal models have demonstrated that antenatal corticosteroid administration is associated with neurocognitive disabilities (i.e. difficulty learning) and structural brain changes such as reduction in hippocampal volume. Infants born to Zinc-deficient mothers show signs of memory impairment. Across both prenatal exposures, what differentiates the animal from the human studies is access to the neonatal brain. The goal of this project is to assess the influence of maternal prenatal stress and poor nutrition on neonatal brain structure and function, and to relate the imaging measures to cognitive outcomes in early childhood. The pro- posed R01 study is a follow-up to an ARRA-funded R01 assessing biopsychosocial stress and nutrition during adolescent pregnancy. Specifically, we have three primary aims to be carried out with pregnant adolescents (ages 15 -19) and their infants: (1) To determine associations between maternal antenatal stress and nutrition, and variation in newborn brain development (from multi-modal imaging). (2) To determine the neural bases of deficits in specific learning and memory tasks, and a general index of cognitive development, associated with prenatal stress and inadequate nutrition. (3) To determine the bidirectional influences between maternal care (i.e. maternal sensitivity and mother-infant attachment style) and infants'emerging learning and memory capacities. Establishing brain-associated relationships between these prenatal exposures and infant cognition has the potential to help specify the in utero developmental effects of two experiences common to pregnancy, high stress and inadequate nutrition, potentially constraining children's future learning even before birth. Such results would have significant public health relevance with respect to policy and early intervention approaches. They also could contribute to the identification of exposure-related 'brain signatures'to be used for diagnostic and treatment purposes, much as is emerging in imaging studies of depression. PUBLIC HEALTH RELEVANCE: The goal of this project is to assess the relationship between maternal prenatal stress and poor nutrition and newborn babies'brain structure and function, and to relate multi-modal imaging measures (MRI) of the new- born baby's brain to neurocognitive outcomes in early childhood. Establishing brain-associated relationships between these prenatal exposures and infant cognition has the potential to specify how women's experiences during pregnancy influence their baby's development, potentially affecting children's future learning even be- fore birth. These results could be very relevant to public health and could inform policy, early intervention approaches, and help to identify brain features that could inform diagnosis and treatment.

Summary Children's neurocognitive development can cast long shadows on their futures, dramatically influencing their occupational functioning and psychosocial adjustment. While it is increasingly recognized that normative varia- tion in early environmental experiences (i.e. parenting style), plays a significant role in shaping cognitive devel- opment, evidence indicates that the impact of the environment on cognitive development begins in utero. Two common experiences during pregnancy, psychosocial stress and inadequate micronutrient intake - promi- nently, iron and zinc, affect outcomes. Prenatal anxiety predicts delayed mental and motor development on the Bayley Scales in infancy, and a reduction in gray matter in the middle temporal lobe based on brain imaging in school-age children. Animal models have demonstrated that antenatal corticosteroid administration is asso- ciated with neurocognitive disabilities (i.e. difficulty learning) and structural brain changes such as reduction in hippocampal volume. Infants born to Zinc-deficient mothers show signs of memory impairment. Across both prenatal exposures, what differentiates the animal from the human studies is access to the neonatal brain. The goal of this project is to assess the influence of maternal prenatal stress and poor nutrition on neonatal brain structure and function, and to relate the imaging measures to cognitive outcomes in early childhood. The pro- posed R01 study is a follow-up to an ARRA-funded R01 assessing biopsychosocial stress and nutrition during adolescent pregnancy. Specifically, we have three primary aims to be carried out with pregnant adolescents (ages 15 -19) and their infants: (1) To determine associations between maternal antenatal stress and nutrition, and variation in newborn brain development (from multi-modal imaging). (2) To determine the neural bases of deficits in specific learning and memory tasks, and a general index of cognitive development, associated with prenatal stress and inadequate nutrition. (3) To determine the bidirectional influences between maternal care (i.e. maternal sensitivity and mother-infant attachment style) and infants' emerging learning and memory ca- pacities. Establishing brain-associated relationships between these prenatal exposures and infant cognition has the potential to help specify the in utero developmental effects of two experiences common to pregnancy, high stress and inadequate nutrition, potentially constraining children's future learning even before birth. Such results would have significant public health relevance with respect to policy and early intervention approaches. They also could contribute to the identification of exposure-related 'brain signatures' to be used for diagnostic and treatment purposes, much as is emerging in imaging studies of depression.

DESCRIPTION (provided by applicant): Major climatic events, such as hurricanes, appear to be increasing due to the consequences of global warming. Such events are likely associated with increased psychological stress. On October 29, 2012 Superstorm Sandy, a major hurricane, devastated the mid-Atlantic region of the United States, particularly the New York City/New Jersey area. Pregnant women are considered a vulnerable population and there is increasing evidence that acute psychosocial stressors may be associated with adverse pregnancy outcomes, such as decreases in birth weight and decreases in gestational length. Further, maternal exposure to stressful events may be associated with decreases in leukocyte telomere length (LTL) in the newborn. Capitalizing on a birth cohort currently being recruited, we propose a study to examine associations between exposure to Superstorm Sandy and pregnancy outcomes and newborn LTL. This study improves on previous studies of natural and manmade disasters because we will be able to parse exposure to specific trimesters and to the three months prior to conception; we have place controls, i.e. a cohort being recruited in an unaffected area using exactly the same measures; we have baseline information on maternal perceived stress, depression, anxiety, social support and resilience, and we have an adequate sample size to address the aims. Results from this study have the potential to inform emergency responders and clinicians how best to support and potentially mitigate the effects of psychological stress among pregnant women after a major natural disaster. Results will also set the stage for studies to inquire whether prenatal exposure to stressful events is associated with cognitive and behavioral problems in children.

PROJECT SUMMARY/ABSTRACT Of the nearly 4 million live births each year in the United States, approximately 560,000, or 14% of these women will develop depression within the first four months postpartum. The consequences are substantial: diminished quality of life and significant emotional suffering for women. PPD predicts diminished mother?infant bonding and poor outcomes in social?emotional and, for some, cognitive development. Relying on standard pharmacologic and psychological interventions, PPD is undertreated in part because women are reluctant to seek treatment due to the stigma associated with mental health care, logistical barriers to attending added health care appointments, and disinclination to take medications while breastfeeding. Risk factors for PPD are relatively well delineated. Even though prenatal depressive symptoms are some of the most reliable predictors, evidenced?based, preventive interventions for PPD are rare. Of the preventative interventions, few leverage the unique dyadic orientation of the childbearing period or imbed services in obstetrical care. To address the huge knowledge gap in the prevention and treatment of PPD, we developed (R21MH092665?01) and tested in a preliminary randomized control trial (RCT) a new intervention called PREPP (Practical Resources for Effective Postpartum Parenting) and, following promising published data, we propose to conduct a larger RCT of this treatment. PREPP enrolls pregnant women at risk for PPD, spans late pregnancy to the 6? week postpartum check up. It consists of four in?person `coaching' sessions adjunctive to obstetrical (OB) prenatal and postnatal appointments, and one phone session. PREPP includes (a) mindfulness and self? reflection skills, (b) parenting skills and (c) psycho?education. For this proposed project, we have three study aims to be realized in a PREPP vs Enhanced Treatment as Usual RCT of 214, 3rd trimester pregnant women (ages 18?35) at risk for PPD assessed 2x in pregnancy and at 6, 12, and 16 weeks postpartum: (1) Reduce women's distress during pregnancy (2) Determine the maintenance of improved maternal mood and differences in infant behavior (3) Identify some of the pathways by which PREPP positively affects the mother? infant dyad. PREPP is innovative in its novel conceptualization of PPD and design to overcome barriers to PPD treatment. The traditional clinical approach to PPD has as a focus the individual and improving their symptoms. In PREPP, PPD is viewed as a potential disorder of the mother?infant dyad, which can be approached through preventive psychological and behavioral changes in the mother ? commencing before birth ? that affect her and the child. PREPP exemplifies the vanguard of health care innovations aiming to increase metal health care uptake by integrating behavioral health services with primary health care. The proposed research is significant because it is expected to advance the treatment and prevention of PPD, and generate new knowledge about mother?infant behav-ioral influences during the first months of postnatal life.

PROJECT SUMMARY Self-regulatory deficits are common across a variety of childhood psychiatric disorders in which children have difficulty regulating their thoughts, emotions, and behaviors. By leveraging previously collected prenatal and neonatal data and acquiring new data from mother-infant dyads, this study will identify circuit-based markers of regulatory deficits that are passed inter-generationally, and persist from infancy to childhood. We will enroll 15- 45 year-old pregnant women/mothers, approximately 75% Latina, who are receiving health care from our ur- ban medical center, a sample that is underrepresented in U.S. biomedical research and facing significant psy- chosocial adversity. Age-appropriate measures of regulatory control processes will be acquired from their off- spring at 4- and 14-months and during preschool and school age, including resting-state fMRI data from neo- nates and both resting and task-based fMRI data from school-aged children who were previously scanned as neonates. Behavioral measures of regulatory capacity and resting and task-based fMRI will also be acquired from the mothers, allowing us to associate maternal-neonatal indices of self-regulatory control. Thus, this study will uncover trajectories of control processes and circuits from infancy to school age and the intergenerational transmission of regulatory deficits from mothers to offspring. Findings will set the stage for future research aimed at engaging these circuits as targets for strategies to prevent the risk for future maladaptive behaviors and at identifying prenatal mechanisms underlying the intergenerational transmission of regulatory deficits, such as epigenetic and stress-mediated biological alterations. This study supports the NIMH strategic objective to chart mental illness trajectories to determine when, where, and how to intervene by elucidating the develop- ment of regulatory control across the first decade of life. This study also supports both the NIH BRAIN and pre- cision medicine initiatives by evaluating the functional organization of control circuits across family generations and longitudinally, as well as using a novel imaging method to predict behavioral outcomes.

ABSTRACT The devastating effects of the COVID-19 pandemic have reverberated through every aspect of our civilization. While SARS-CoV-2, the viral etiology of COVID-19, seems to spare infants in terms of actual infection, it is currently unknown whether maternal infection during pregnancy will have long-term effects on children born during the pandemic. A variety of prenatal insults, including infections and stress, are well-known to lead to increased risk of affective disorders in both mother and child. With its disproportionate reach into already disadvantaged minority communities, the impact of the COVID-19 pandemic on the dyad is currently unknown and potentially of unprecedented magnitude with enduring consequences for women's mental health and children's developmental origins of health and disease (DOHaD). The COVID-19 Mother Baby Outcome (COMBO) initiative, a large multidisciplinary collaborative, was established at Columbia University Irving Medical Center to follow SARS-CoV-2 exposed laboring mothers and their newborns and compare their long- term health outcomes to case-matched dyads without prenatal exposure. This proposal will follow a subset of the larger COMBO cohort to study socioemotional circuits (fronto-limbic) and behavior (caregiving and bonding) in 100 mother-child dyads from prepartum to 18 months postpartum. The team assembled to carry out this study consists of two provider scientists (Dumitriu, pediatrician and neuroscientist, & Monk, clinical psychologist embedded in Ob/Gyn) and neuroscientist/pediatric neuroimager (Marsh). Using an innovative dyadic approach, olfaction testing, multimodal MRI, wearable in-home physiological recordings, observational mother and child assessments (free play, routine care, Harvard Reactivity and Still Face paradigms), this proposal will test the overarching hypothesis that prenatal SARS-CoV-2 exposure affects (1) mother and (2) child brain and behavior, and (3) demonstrate that the socioemotional health of each member of the mother- child dyad is intrinsically related to that of the other. Detecting COVID-19-related early neurobehavioral effects on mothers and the next generation will provide insights into intervention strategies and contribute significantly to DOHaD and stress science.

PROJECT ABSTRACT At odds with common assumptions ? and hope, pregnancy ends in preterm birth (PTB) for approximately 1 in 10 women. Yearly PTB affects 15 million infants worldwide and 386,580 in the United States. PTB is the leading cause of global, and U.S., neonatal mortality and morbidity and is associated with future risk for poor physical (higher blood pressure, chronic kidney disease, wheeze/asthma) and mental (ADHD, IQ decrements) health. Maternal health is not spared: women who deliver preterm are at an increased risk for depression, hypertension, cardiovascular and renal disease later in life. In the U.S., the racial and ethnic disparities in PTB rates are dramatic and independent of socio-economic status (SES): overall, 14.12% for Non-Hispanic Black compared to 9.09% for Non-Hispanic White women. Psychosocial stress and childhood trauma each are associated with risk for PTB. PTB has an intergenerational impact: mothers born preterm are more likely to give birth pretern, especially amongst Black women. Biomarkers to predict PTB have proven unsuccessful, and do not account for this emerging recognition of intergenerational transmission of PTB risk specifically via maternal heritage. Mitochondria, which contain their own genome, the mitochondria DNA, are inherited from the mother and represent a potential intersection point between psychosocial experiences and their biological embedding, including via immune dysregulation, in underlying disease outcomes. We aim to apply a mitochondria psychobiology approach to delineate by which mechanisms life stress ? including discrimination and childhood trauma ? results in disproportionate risk of PTB in minority women, and evaluate mitochondria as potential biomarkers of this birth outcome. In a sample of post-attrition n=175 pregnant women we will test the following three aims: Aim 1: To determine whether a data driven approach to multiple, 1st trimester psychosocial (self- report stress discrimination, 24-hour ambulatory mood, social support), lifecourse (hair cortisol, childhood trauma), and biological variables (acute laboratory physiological stress reactivity) generate unique stress profiles that partially explain the racial/ethnic differences in gestational age at birth. Aim 2: To identify molecular indices of mitochondrial and immune functioning in the mother (3x blood draw), placenta, and fetal cord blood that mediate the association between 1st trimester maternal stress phenotypes and risk for earlier gestational age at birth. Aim 3: To evaluate if reduction in stress levels and/or improvement in social support over the course of pregnancy is associated with molecular indices of mitochondrial and immune functioning and (exploratory) reduced risk of earlier birth relative to national and hospital norms. This new conceptual framing of this adverse health outcome (1) incorporates evidence of the psychosocial factors contributing to risk, (2) aims to account for the racial/ethnic disparities, and (3) harnesses cutting-edge mitochondria knowledge and tools to better characterize PTB?s pathophysiology and identify novel targets for its intervention and prevention.

ABSTRACT The COVID-19 pandemic has highlighted and exacerbated health disparities related to structural racism and discrimination (SRD), economic marginalization, and other social determinants of health (SDOH). Pregnant and postpartum women face unique social and health vulnerabilities related to the pandemic, including risk for stigma, housing, food, income and employment insecurity, psychological distress, and even mortality ? risks and consequences which are disproportionately significant and adverse for women of color and low socioeconomic status (SES). However, the collision of these multiple intersecting 21st century public health crises have not yet been empirically or rigorously studied for inequities in maternal mental health and severe morbidity. The COVID-19 Mother Baby Outcome (COMBO) initiative is a large multidisciplinary collaborative established at Columbia University Irving Medical Center to follow SARS-CoV-2 exposed laboring mothers and their newborns and compare their long-term health and wellbeing to case-matched dyads without prenatal exposure. The focus of the parent NIMH ?COMBO? R01 MH126531 is to understand the effects of SARS-CoV- 2 on mother-infant brain-behavior functioning in a subset of 100 COMBO-enrolled dyads with and without prenatal SARS-COV-2 infections. Responding to key priorities of NOSI NOT-OD-21-071 and leveraging COMBO?s robust infrastructure, this administrative supplement (PA-20-272) expands the parent R01 to study the independent and interactive effects of SRD/SDOH and SARS-CoV-2 on inequities in maternal mental health, taking advantage of COMBO?s unique setting (first pandemic epicenter) and understudied socially disadvantaged sample (>600 mother-infant dyads enrolled to-date, with 63% mothers identifying as racial/ethnic minority and/or low-SES women). By expanding parent R01 brain imaging, surveys, semi- structured interviews, and electronic health record (EHR) extraction, we will test the overarching hypothesis that SRD/SDOH and SARS-CoV-2 independently and additively increase risk of adverse maternal mental health outcomes, with the magnitude of the negative impact being greatest for women of social disadvantage and the health disparity gap ballooning during ? and persisting post ? the pandemic. Findings will inform patient-centered, multi-level interventions to ameliorate the intersecting epidemics of SRD/SDOH and SARS- CoV-2 and their mental health sequelae for women of social disadvantage in NYC and beyond.