It is well established that childhood adversity is one of the most potent predictors of adult affective disorders, particularly among women. Further, an important dissociation has been reported for a subgroup of women who experience early life adversity but do not present with adult disease, suggesting that there may be resiliency factors important in disease protection or amelioration. In fact, the availability of a caring and stable parent or guardian has been shown to be one of the most important aspects that distinguish between positive and negative outcomes in abused individuals. We propose that one vital contributor to the increased risk for major depressive disorder (MOD) in women, and propensity for other affective disturbances at specific reproductive time points, is the programming effect of prepubertal adversity on dysregulation of hypothalamic pituitary adrenal (HPA) activity and ovarian steroid responsiveness across the lifespan. It is well documented that from puberty to the late perimenopause, MOD and several anxiety disorders are more common in females than males. Moreover, periods of hormonal flux across the female lifespan are associated with increased risk for affective disturbance: the premenstrum (premenstrual dysphoric disorder), the postpartum (onset/relapse bipolar disorder, MOD), and the perimenopause (depression symptoms and MDD. The goal of the scientific Projects in this SCOR proposal is to determine how the experience of prepubertal adversity reprograms the brain toward stress dysregulation, and how this intersects with periods of dynamic hormonal flux across the life span, including pregnancy (Projects I & III) and aging (Projects II & III). In addition, mechanistic epigenetic studies will examine sex differences in response to stress during this sensitive window of brain maturation (Project III). SCOR funding would harness the respective expertise of Drs. Epperson and Bale in behavioral and molecular models of stress and reproductive neuroendocrinology, psychophysiology, and neuroimaging, to create the Penn Center for the Study of Sex and Gender in Behavioral Health. The Center would provide an intellectual platform with important resources to encourage established investigators, and their mentees, to consider sex and gender as crucial factors in their research.

Public Health Relevance

Early life adversity is one of the greatest predictors of affective disorder onset in women. That gonadal steroids impact the initiation and maintenance of the stress response suggests that these systems are critical to the sex differences observed in neuropsychiatric and substance use disorders, as well as medical conditions such as autoimmune disorders, cardiovascular disease, obesity, and migraines to name a few.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH099910-04
Application #
8902955
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Zehr, Julia L
Project Start
2012-08-06
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Cooney, Laura G; Milman, Lauren W; Hantsoo, Liisa et al. (2018) Cognitive-behavioral therapy improves weight loss and quality of life in women with polycystic ovary syndrome: a pilot randomized clinical trial. Fertil Steril 110:161-171.e1
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
Hantsoo, Liisa; Podcasy, Jessica; Sammel, Mary et al. (2017) Pregnancy and the Acceptability of Computer-Based Versus Traditional Mental Health Treatments. J Womens Health (Larchmt) 26:1106-1113
JaĊĦarevi?, Eldin; Howard, Christopher D; Misic, Ana M et al. (2017) Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner. Sci Rep 7:44182
Di Florio, A; Putnam, K; Altemus, M et al. (2017) The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale. Psychol Med 47:787-799

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