Exposure to maternal depression during pregnancy is common and associated with adverse medical and behavioral outcomes in infants. However, little is known about mechanisms underlying early adverse effects. This information is critical for early identification and intervention efforts with high-risk infants. In animal models, maternal prenatal stress results in long-term dysregulation (""""""""programming"""""""") of the hypothalamic pituitary adrenocortical (HPA) stress response and neurobehavior. Prominent mechanisms underlying effects of prenatal stress in animals involve increases in maternal glucocorticoids and downregulation of placental 11? hydroxysteroid dehydrogenase type 2 (11? HSD 2), an enzyme that inactivates cortisol to cortisone. Our group has begun to translate this animal work to humans. We have shown effects of maternal depressive symptoms on fetal and neonatal stress response and neurobehavior. We have also shown that placental 11? HSD 2 is downregulated by norepinephrine, which is, in turn, regulated by the placental norepinephrine transporter (NET). Critical next steps in our program of research and the field are to determine effects of major depressive disorder (MDD) rather than depressive symptoms on fetal/neonatal stress response and neurobehavior, and to elucidate pathways linking prenatal MOD to fetal/neonatal neurobehavioral dysregulation. Thus, our aims are: 1) to characterize effects of pregnancy MDD on fetal and neonatal stress response and neurobehavior, 2) to test the hypothesis that maternal MDD influences fetal/neonatal stress response via alterations in maternal cortisol, and downregulation of placental NET and 11? HSD 2. In response to reviewer concerns, we added an exploratory aim to examine effects of comorbid MDD + anxiety disorders relative to MDD-only on fetal/neonatal neurobehavior and maternal-placental HPA regulation. This revised application proposes an intensive, longitudinal investigation of maternal MDD, maternal-placental neuroendocrine dysregulation, and fetal/neonatal stress response and neurobehavior. Three groups of mothers and offspring will be identified: a) mothers with MDD during pregnancy (including MDD- only and MDD + anxiety disorder), b) mothers with a history of MDD who remain euthymic during pregnancy, and c) mothers with no history of or current psychiatric disorder (controls). Neonatal assessment will involve cortisol and behavioral response to a neurobehavioral examination at 1-2 and 30 days; fetal assessment will include heart rate and behavioral response to vibroacoustic stimulus. Measures of maternal-placental neuroendocrine regulation will include maternal circadian cortisol, and placental NET and 11? HSD 2 gene expression. Results may elucidate early markers of risk and help to delineate early pathways to later behavioral dysregulation. Early identification of high-risk fetuses and infants may also lead to education for parents to improve interactions with stressed newborns, and, potentially, novel therapeutic targets to protect fetuses from consequences of maternal depression. ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH079153-01A1
Application #
7320395
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Delcarmen-Wiggins, Rebecca
Project Start
2007-09-01
Project End
2012-07-31
Budget Start
2007-09-01
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$648,113
Indirect Cost
Name
Miriam Hospital
Department
Type
DUNS #
063902704
City
Providence
State
RI
Country
United States
Zip Code
02906
Bublitz, Margaret H; Bourjeily, Ghada; D'Angelo, Christina et al. (2018) Maternal Sleep Quality and Diurnal Cortisol Regulation Over Pregnancy. Behav Sleep Med 16:282-293
Aubuchon-Endsley, Nicki; Morales, Monique; Giudice, Christina et al. (2017) Maternal pre-pregnancy obesity and gestational weight gain influence neonatal neurobehaviour. Matern Child Nutr 13:
Salisbury, Amy L; O'Grady, Kevin E; Battle, Cynthia L et al. (2016) The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month. Am J Psychiatry 173:147-57
Bublitz, Margaret H; Vergara-Lopez, Chrystal; O'Reilly Treter, Maggie et al. (2016) Association of Lower Socioeconomic Position in Pregnancy with Lower Diurnal Cortisol Production and Lower Birthweight in Male Infants. Clin Ther 38:265-74
Stroud, Laura R; Papandonatos, George D; Parade, Stephanie H et al. (2016) Prenatal Major Depressive Disorder, Placenta Glucocorticoid and Serotonergic Signaling, and Infant Cortisol Response. Psychosom Med 78:979-990
Aubuchon-Endsley, Nicki L; Bublitz, Margaret H; Stroud, Laura R (2014) Pre-pregnancy obesity and maternal circadian cortisol regulation: Moderation by gestational weight gain. Biol Psychol 102:38-43
Bublitz, Margaret H; Parade, Stephanie; Stroud, Laura R (2014) The effects of childhood sexual abuse on cortisol trajectories in pregnancy are moderated by current family functioning. Biol Psychol 103:152-7
Bublitz, Margaret H; Rodriguez, Daniel; Polly Gobin, Asi et al. (2014) Maternal history of adoption or foster care placement in childhood: a risk factor for preterm birth. Am J Obstet Gynecol 211:397.e1-6
Bublitz, Margaret H; Stroud, Laura R (2013) Maternal history of child abuse moderates the association between daily stress and diurnal cortisol in pregnancy: a pilot study. Stress 16:706-10
Bublitz, Margaret H; Stroud, Laura R (2012) Childhood sexual abuse is associated with cortisol awakening response over pregnancy: preliminary findings. Psychoneuroendocrinology 37:1425-30

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