The focus of this application is on the developmental consequences for children exposed to stress during gestation. One of the major placental stress signals in pregnant primates is the peptide corticotrophin-releasing hormone (CRH). This peptide plays a key role in the maturation of the fetal hypothalamic-pituitary-adrenal (HPA) axis and it synchronizes events that underlie fetal growth and maturation. Placental CRH is responsive to all the major biological signals of stress in the maternal and fetal compartments. Stress-related alterations in the normal pattern of placental CRH production during pregnancy have major implications for childhood development. Extensive research supports the conclusion that placental CRH is the stress index consistently associated with birth outcomes, however placental CRH has not been used to predict neurodevelopmental outcomes. The focus on placental CRH capitalizes on a direct index of fetal experience and avoids the assumption that maternal stress results in a coherent and consistent maternal physiological profile that is transmitted to the fetus. We propose to assess 600 children (between the ages of 6-0 and 7-11 years) for whom we have extensive histories of prenatal stress exposure and birth phenotypes with measures of (a) emotional regulation; (b) cognition; (c) anatomy of brain structures (using structural magnetic resonance imaging (MRI); and (d) regulation of the HPA stress axis. Influences of prenatal CRH on emotional regulation (Aim 1) will be evaluated by examining the relation between levels of CRH with measures of parent and self-report of temperament. Programming effects of early exposure to CRH on cognition (Aim 2) will be evaluated by examining the relation between levels of placental CRH and performance on standardized measures of intelligence and novel measures of attention, memory and executive function. The effects of prenatal exposure to CRH on the volume of the hippocampus, amygdala and prefrontal cortex (Aim 3) will be evaluated in a subgroup of 80 children in the upper and lower quintile of third trimester CRH level. Prenatal influences of CRH on HPA reactivity (Aim 4) will be evaluated by assessing salivary cortisol at rest and after mild stress. These studies in children are the first to examine the role of prenatal CRH on human development. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD051852-02
Application #
7284823
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Freund, Lisa S
Project Start
2006-09-15
Project End
2011-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$520,812
Indirect Cost
Name
University of California Irvine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Riley, Jeffrey D; Chen, E Elinor; Winsell, Jessica et al. (2018) Network specialization during adolescence: Hippocampal effective connectivity in boys and girls. Neuroimage 175:402-412
Sandman, Curt A; Curran, Megan M; Davis, Elysia Poggi et al. (2018) Cortical Thinning and Neuropsychiatric Outcomes in Children Exposed to Prenatal Adversity: A Role for Placental CRH? Am J Psychiatry 175:471-479
Glynn, Laura M; Stern, Hal S; Howland, Mariann A et al. (2018) Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood. Neuropsychopharmacology :
Davis, Elysia Poggi; Head, Kevin; Buss, Claudia et al. (2017) Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood. Psychoneuroendocrinology 75:56-63
Hankin, Benjamin L; Davis, Elysia Poggi; Snyder, Hannah et al. (2017) Temperament factors and dimensional, latent bifactor models of child psychopathology: Transdiagnostic and specific associations in two youth samples. Psychiatry Res 252:139-146
Howland, Mariann A; Sandman, Curt A; Glynn, Laura M (2017) Developmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Rev Endocrinol Metab 12:321-339
Snyder, Hannah R; Hankin, Benjamin L; Sandman, Curt A et al. (2017) Distinct patterns of reduced prefrontal and limbic grey matter volume in childhood general and internalizing psychopathology. Clin Psychol Sci 5:1001-1013
Davis, Elysia Poggi; Stout, Stephanie A; Molet, Jenny et al. (2017) Exposure to unpredictable maternal sensory signals influences cognitive development across species. Proc Natl Acad Sci U S A 114:10390-10395
Curran, Megan M; Sandman, Curt A; Poggi Davis, Elysia et al. (2017) Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity? PLoS One 12:e0180311
Kim, Dae-Jin; Davis, Elysia Poggi; Sandman, Curt A et al. (2016) Children's intellectual ability is associated with structural network integrity. Neuroimage 124:550-556

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