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 (50))
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University of Pennsylvania
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Goel, Namni; Bale, Tracy L; Epperson, C Neill et al. (2014) Effects of sex and gender on adaptation to space: behavioral health. J Womens Health (Larchmt) 23:975-86
Howerton, Alexis R; Roland, Alison V; Bale, Tracy L (2014) Dorsal raphe neuroinflammation promotes dramatic behavioral stress dysregulation. J Neurosci 34:7113-23
Howerton, Christopher L; Bale, Tracy L (2014) Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction. Proc Natl Acad Sci U S A 111:9639-44
Altemus, Margaret; Sarvaiya, Nilofar; Neill Epperson, C (2014) Sex differences in anxiety and depression clinical perspectives. Front Neuroendocrinol 35:320-30
Morrison, K E; Rodgers, A B; Morgan, C P et al. (2014) Epigenetic mechanisms in pubertal brain maturation. Neuroscience 264:17-24
Kim, Deborah R; Hantsoo, Liisa; Thase, Michael E et al. (2014) Computer-assisted cognitive behavioral therapy for pregnant women with major depressive disorder. J Womens Health (Larchmt) 23:842-8
Hantsoo, Liisa; Ward-O'Brien, Deborah; Czarkowski, Kathryn A et al. (2014) A randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression. Psychopharmacology (Berl) 231:939-48
Boersma, G J; Bale, T L; Casanello, P et al. (2014) Long-term impact of early life events on physiology and behaviour. J Neuroendocrinol 26:587-602
Epperson, C Neill; Kim, Deborah R; Bale, Tracy L (2014) Estradiol modulation of monoamine metabolism: one possible mechanism underlying sex differences in risk for depression and dementia. JAMA Psychiatry 71:869-70
Hantsoo, Liisa; Czarkowski, Kathryn A; Child, Josiah et al. (2014) Selective serotonin reuptake inhibitors and endothelial function in women. J Womens Health (Larchmt) 23:613-8

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