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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZRG1-EMNR-Q)
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University of Pennsylvania
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Morrison, Kathleen E; Narasimhan, Sneha; Fein, Ethan et al. (2016) Peripubertal Stress With Social Support Promotes Resilience in the Face of Aging. Endocrinology 157:2002-14
Jašarević, Eldin; Morrison, Kathleen E; Bale, Tracy L (2016) Sex differences in the gut microbiome-brain axis across the lifespan. Philos Trans R Soc Lond B Biol Sci 371:20150122
Smith, Ariana L; Hantsoo, Liisa; Malykhina, Anna P et al. (2016) Basal and stress-activated hypothalamic pituitary adrenal axis function in postmenopausal women with overactive bladder. Int Urogynecol J 27:1383-91
Bronson, Stefanie L; Bale, Tracy L (2016) The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming. Neuropsychopharmacology 41:207-18
Morrison, Kathleen E; Epperson, C Neill; Sammel, Mary D et al. (2016) Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice. Biol Psychiatry :
Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D et al. (2015) Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain. Endocrinology 156:3265-76
Kim, Deborah R; Bale, Tracy L; Epperson, C Neill (2015) Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep 17:5
Hantsoo, Liisa; Epperson, C Neill (2015) Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Curr Psychiatry Rep 17:87
Epperson, C Neill; Shanmugan, Sheila; Kim, Deborah R et al. (2015) New onset executive function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology (Berl) 232:3091-100
Nugent, Bridget M; Bale, Tracy L (2015) The omniscient placenta: Metabolic and epigenetic regulation of fetal programming. Front Neuroendocrinol 39:28-37

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