Mood, Mother and Child: The Psychobiology of Dyadic Resilience
NICHD R01HD093901
Perinatal depression (PND) affects more than 400,000 mother-infant dyads in the US each year, with devastating consequences. Mothers with PND exhibit reduced sensitivity to infant needs, increasing infant risk for impaired emotional regulation and insecure attachment. These dysregulated interactions in the first year of life are associated with impaired cognitive and socioemotional development, including child psychopathology and impaired executive function (EF). Mothers who experience PND are more likely to have continuing or relapsing depression and anxiety disorders, conferring further risk. Nevertheless, despite exposure to PND, some dyads emerge intact. The long-term goal of this research is to identify the psychobiological underpinnings of resilience among mother-child dyads exposed to PND and longer-term maternal depression and anxiety trajectories (MDATs). The objectives of this proposal are to characterize MDAT heterogeneity during the first 5 years of the child’s life, to identify mediators that explain the mechanisms through which MDATs influence child outcomes, and identify moderators that may serve as intervention points for promoting dyadic resilience. We will leverage an existing pool of participants in the Mood, Mother and Infant (MMI) study (R01HD073220, mmi.web.unc.edu, PI Stuebe), an ongoing longitudinal cohort study that we have led of mother-infant dyads (N=222) who have been extensively phenotyped during the first postpartum year. Our central hypothesis is that oxytocin plays a central role in dyadic development, indexed by associations between OT psychobiology, genetics and epigenetics and both MDATs and child development outcome. The rationale for this work is that our findings will inform targeted interventions to facilitate resilience and diminish the sequelae of maternal depression. We will accomplish the objective of our application by pursuing the following specific aims via an MMI follow-up study, the Mood, Mother and Child (MMC) study: 1) Elucidate the role of OT in the maternal psychobiological underpinnings of MDATs and parenting behavior, including effects of exogenous oxytocin (OT) on HPA axis reactivity; 2) Determine psychosocial mediators and moderators of associations between MDATs and child developmental outcome; and 3) Determine the extent to which child OXT and OXTR genotype moderates associations between MDATs, sensitivity, attachment quality, and developmental outcome; quantify the extent to which child epigenetic changes in OT and OXTR mediate associations between MDATs and developmental outcome. The expected outcomes of this work will be the determination of both predictive and protective factors for mother-infant dyads affected by depression and anxiety, laying the groundwork for novel approaches to promote resilience. Such results will have a positive impact by informing interventions to prevent intergenerational transmission of depression and anxiety.
Mood, Mother and Infant: The psychobiology of impaired dyadic development
NICHD R01HD073220
Postpartum depression (PPD) is a common, morbid condition that affects 10-15% of mothers. Recent work implicates reductions in oxytocin, a neuropeptide that plays a central role in mothering and social behavior, in the pathophysiology of this disorder. The proposed study will use lactation as a novel physiologic challenge to determine the extent to which low oxytocin mediates associations between PPD and impaired development of the mother-infant dyad. The long-term goal of this research is to identify mother-infant dyads at risk of PPD and implement targeted interventions to address their personal neuroendocrine vulnerabilities, thereby improving the health of mother and child. The objective here is to define the role of oxytocin and dysregulated stress reactivity in the psychobiology of PPD and impaired dyadic development, indexed by maternal sensitivity, infant emotional regulation, and insecure attachment. The central hypothesis is that PPD is associated with reduced oxytocin and maternal HPA axis dysregulation, indexed by loss of expected associations between ACTH and cortisol. These changes reduce maternal sensitivity, impairing dyadic development and increasing risk for insecure attachment. This hypothesis has been formulated based on published literature and preliminary data showing diminished oxytocin and dysregulation of the HPA axis among women with PPD symptoms. The rationale for this work is that as the underlying mechanisms of PPD are identified, interventions can be developed to target at-risk dyads and diminish PPD and its sequelae for mother and infant. Guided by strong preliminary data, the central hypothesis will be tested by pursuing three specific aims: 1. Use lactation as a physiologic challenge to quantify the extent to which PPD reduces oxytocin, dysregulates stress reactivity, and diminishes maternal sensitivity; 2. Use standardized mother-infant interactions to determine the extent to which PPD and reduced maternal sensitivity impair development of infant emotional regulation and increase risk for insecure attachment; 3. Determine the extent to which diminished maternal oxytocin and reduced sensitivity mediate associations between PPD, impaired infant emotional regulation, and insecure attachment. These aims will be achieved through a longitudinal study of 200 mother-infant dyads spanning late pregnancy through 12 months postpartum, half with a history of depression and/or anxiety and half with no psychiatric history, confirmed by diagnostic interview. Mother-infant dyads will be assessed during visits to the Mother-Infant Biobehavioral Lab. The approach is innovative, because this project will use lactation as a physiologic challenge to quantify intersections among maternal oxytocin physiology, stress reactivity, caregiving, emotional regulation, and attachment, thereby shedding light on both maternal mental health and infant emotional development. The proposed research is significant, because it is expected to define the role of oxytocin in PPD and impaired dyadic development. Ultimately, such knowledge has the potential to inform novel therapies to prevent PPD and reduce its sequelae for mother and child.
This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development R01 HD073220, Mood, mother and infant: The psychobiology of impaired dyadic development, and R01HD093901, Mood, Mother and Child: The Psychobiology of Dyadic Resilience.
Study Team
Samantha Meltzer-Brody, MD, MPH