The hypothalamic-pituitary-adrenal (HPA) axis mediates many adaptations to stress, and HPA dysfunction occurs in depression and other stress-related disorders. During pregnancy, HPA-related mechanisms mediate stress-related communication between the maternal and fetal compartments through the placenta, which secretes corticotrophin-releasing hormone (CRH). The overarching hypothesis guiding Project 2 is that fetal and encoding key components of the hypothalamic-pituitary-adrenal (HPA) axis substantially influence fetal vulnerability to intrauterine exposures and maternal emotional distress by modulating (i) the sensitivity of the fetus to the milieu, and (ii) fetal-maternal communication mediated by the placenta. We will use family-based association methods (FBAT and PBAT) to address that hypothesis, by pursuing' the following Specific Aims: (1) examine the effects of maternal stress and fetal genotypes on placental expression of HPA-related genes, (2) examine the relationship among fetal polymorphisms in HPA-related genes and maternal and fetal serum concentrations of CRH, CRHBP and cortisol, (3) test the association of fetal genotypes and haplotypes of HPA-axis related genes with fetal and neonatal outcome (uterine blood flow, birth weight and infant cortisol response after inoculation and strange situation), and (4) test for gene x environment interactions, the environment being low vs. high maternal stress during pregnancy on the outcomes examined in Specific Aims 2 and 3. Public-health relevance: Increasing evidence suggests that maternal depression and other stress-related disorders occurring during pregnancy negatively impact fetal and infant outcomes. HPA-related mechanisms appear to be critical mediators and modulators of the relationship between maternal stress and depression, and such outcomes. Understanding whether and how variation at specific HPA-axis-related genes alters the vulnerability of offspring to maternal stress and depression may elucidate the role of the gene products they encode in negative (and positive) fetal and infant outcomes. Such knowledge will facilitate early-intervention strategies for at-risk children, and their mothers

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National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1)
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Emory University
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Gustafsson, Hanna C; Goodman, Sherryl H; Feng, Tianshu et al. (2018) Major depressive disorder during pregnancy: Psychiatric medications have minimal effects on the fetus and infant yet development is compromised. Dev Psychopathol 30:773-785
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
Putnam, Karen T; Wilcox, Marsha; Robertson-Blackmore, Emma et al. (2017) Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium. Lancet Psychiatry 4:477-485
Neigh, Gretchen N; Nemeth, Christina L; Kelly, Sean D et al. (2017) Prenatal stress-induced increases in hippocampal von Willebrand factor expression are prevented by concurrent prenatal escitalopram. Physiol Behav 172:24-30
Lusby, Cara M; Goodman, Sherryl H; Yeung, Ellen W et al. (2016) Infant EEG and temperament negative affectivity: Coherence of vulnerabilities to mothers' perinatal depression. Dev Psychopathol 28:895-911
House, Samuel J; Tripathi, Shanti P; Knight, Bettina T et al. (2016) Obsessive-compulsive disorder in pregnancy and the postpartum period: course of illness and obstetrical outcome. Arch Womens Ment Health 19:3-10
Knight, Anna K; Craig, Jeffrey M; Theda, Christiane et al. (2016) An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biol 17:206
Johnson, Katrina C; Smith, Alicia K; Stowe, Zachary N et al. (2016) Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function. J Clin Psychiatry 77:e176-82
Ehrlich, David E; Neigh, Gretchen N; Bourke, Chase H et al. (2015) Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats. Neuropharmacology 97:251-8
Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium (2015) Heterogeneity of postpartum depression: a latent class analysis. Lancet Psychiatry 2:59-67

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