Pregnancy is a unique period in a woman's emotional life, as she becomes a mother and reflects upon her own parenting and experience as a child. Pregnancy is also a unique period in a woman's endocrine life when sex steroids are at 10- to 100- fold their nonpregnancy levels and stress hormones are surging. In fact, at no other time in human life are both corticotropin releasing factor (CRF) and Cortisol persistently elevated as the placental production of CRF is positively driven by maternal and fetal Cortisol production. Project I serves as the initial segment of the lifespan approach to understanding the effects of prepubertal adversity on brain function as it relates to risk for affective disorders (depression and anxiety) in women. In this project we evaluate a two-generational model of stress by examining the effect of maternal prepubertal adversity on the progeny's health as a way to understand the earliest environmental influence on the biologic development of their offspring. We hypothesize that the effects of maternal past and present experience can be 'transmitted'to the fetus via the exceptional hormonal milieu of the intrauterine environment, programming the offspring's own response to future life events through HPA axis dysregulation. We propose that female infants will be more susceptible to fetal programming than male infants as one explanatory factor for increased prevalence of depression in females compared to males. This project examines maternal and infant HPA axis function and utilizes the well-tolerated acoustic startle paradigm to explore the potential link beh/veen maternal prepubertal adversity and the following outcomes;1) maternal HPA axis responsivity;2) maternal psychophysiology, at baseline and in response to affect modulation;3) infant behavioral and HPA axis response to stress;and 4) sex difference in infant outcomes. In addition, this project will serve as the basis for future exploration of the potential interaction between prepubertal adversity and serotonin and stress system genes in the sex bias for MDD and other disorders for which sex differences have been noted.

Public Health Relevance

Prepubertal trauma is one of the greatest predictors of affective disorder onset in women. Pregnancy is a particularly critical time in the potential transmission of stress-induced dysregulation in maternal psychophysiology and HPA axis fuction to the offspring. Understanding factors that may contribute to this h/vo generation model for HPA axis dysregulation is crucial if effective interventions are to be identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH099910-02
Application #
8522237
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$203,982
Indirect Cost
$76,493
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Hantsoo, Liisa; Golden, Carla E M; Kornfield, Sara et al. (2018) Startling Differences: Using the Acoustic Startle Response to Study Sex Differences and Neurosteroids in Affective Disorders. Curr Psychiatry Rep 20:40
Bromberger, Joyce T; Epperson, Cynthia Neill (2018) Depression During and After the Perimenopause: Impact of Hormones, Genetics, and Environmental Determinants of Disease. Obstet Gynecol Clin North Am 45:663-678
Hantsoo, Liisa; Criniti, Stephanie; Khan, Annum et al. (2018) A Mobile Application for Monitoring and Management of Depressed Mood in a Vulnerable Pregnant Population. Psychiatr Serv 69:104-107
Nugent, Bridget M; O'Donnell, Carly M; Epperson, C Neill et al. (2018) Placental H3K27me3 establishes female resilience to prenatal insults. Nat Commun 9:2555
Chan, Jennifer C; Nugent, Bridget M; Bale, Tracy L (2018) Parental Advisory: Maternal and Paternal Stress Can Impact Offspring Neurodevelopment. Biol Psychiatry 83:886-894
Kornfield, Sara L; Kang-Yi, Christina D; Mandell, David S et al. (2018) Predictors and Patterns of Psychiatric Treatment Dropout During Pregnancy Among Low-Income Women. Matern Child Health J 22:226-236
Epperson, C Neill; Sammel, Mary D; Bale, Tracy L et al. (2017) Adverse Childhood Experiences and Risk for First-Episode Major Depression During the Menopause Transition. J Clin Psychiatry 78:e298-e307
Freeman, Anne; Stanko, Patrick; Berkowitz, Lily N et al. (2017) Inclusion of sex and gender in biomedical research: survey of clinical research proposed at the University of Pennsylvania. Biol Sex Differ 8:22
Kornfield, Sara L; Moseley, Marian; Appleby, Dina et al. (2017) Posttraumatic Symptom Reporting and Reported Cigarette Smoking During Pregnancy. J Womens Health (Larchmt) 26:662-669

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