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Prenatal CRH: An integrating signal of fetal distress

Published online by Cambridge University Press:  02 August 2018

Curt A. Sandman
Curt A. Sandman*
Affiliation:
University of California, Irvine
*
Address correspondence and reprint requests to: Curt A. Sandman, Department of Psychiatry and Human Behavior, University of California, Irvine, One University Drive, Orange, CA 92866; E-mail: casandma@uci.edu.
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Abstract

Corticotropin-releasing hormone (CRH) is distributed throughout the brain and in peripheral sites but primarily is localized in the paraventricular nucleus of the hypothalamus. It is a “master” stress hormone that is responsible for the synthesis of proopiomelanocortin (POMC) in the anterior pituitary gland. Behaviorally active peptide hormones, including adrenocorticotropin hormone (ACTH) and B-endorphin, are liberated from POMC by enzymes to activate critical processes during stress. CRH is not detectable in the circulation even during extreme stress. However, during human pregnancy, the human placenta expresses the gene for CRH (pCRH) resulting in detectable levels in maternal plasma that increases 20- to 40-fold over the course of gestation. Placental CRH is identical to CRH of hypothalamic origin in size, structure, immunoreactivity, and bioactivity. However, unlike the negative feedback between adrenal cortisol and hypothalamic CRH, cortisol stimulates the synthesis and release of pCRH. The bidirectional release of pCRH into maternal and fetal compartments is associated with regulating the timing of delivery, remodeling the fetal nervous system, and influencing developmental trajectories. Fetal exposure to pCRH during early and late gestation is associated with unique patterns of cortical thinning in school-age children. Placental CRH is elevated in response to physical and behavioral stress and may be an integrative marker of early adversity.

Type
Special Issue Articles
Information
Development and Psychopathology , Volume 30 , Special Issue 3: Developmental Origins of Psychopathology: Mechanisms, Processes, and Pathways Linking the Prenatal Environment to Postnatal Outcomes , August 2018 , pp. 941 - 952
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

The research reported here was supported by National Institute of Health Grants NS-41298, HD-51852, HD-28413, HD-40967, HD-50662, and HD-65823, and Conte Center award MH-96889. The invaluable contributions to the research described here by my long-time collaborators, Laura Glynn and Elysia Davis, is gratefully acknowledged. The tireless work of many postdocs and research assistants, especially Claudia Buss, Mariann Howland, Cheryl Crippen, Carol Holliday, Quetzal Class, Christina Canino Brown, Megan Faulkner, Kendra Leak, Amanda Appel, and Kevin Head, made these studies possible. I am forever grateful for the mentoring and friendship of Abba Kastin, who introduced me to the wide world of neuropeptides and the research environment of a laboratory chasing a major discovery. Finally, it is impossible to overestimate the critical contributions by the families who participated in the research program, often making as many as 15, 2- to 3-hr visits to the laboratory and sacrificing weekends and holidays to allow us to learn about the most critical period of human life.

References

Aiken, C. E., & Ozanne, S. E. (2013). Sex differences in developmental programming models. Reproduction, 145, R1–R13.Google Scholar
Avishai-Eliner, S., Brunson, K. L., Sandman, C. A., & Baram, T. Z. (2002). “Stressed-out,” or in (utero)? Trends in Neuroscience, 25, 518–524.Google Scholar
Bale, T. L., Baram, T. Z., Brown, A. S., Goldstein, J. M., Insel, T. R., McCarthy, M. M., … Nestler, E. J. (2010). Early life programming and neurodevelopmental disorders. Biological Psychiatry, 68, 314–319.Google Scholar
Barker, D. J. (1998). Mothers, babies and health in later life. Edinburgh, UK: Churchill Livingston.Google Scholar
Boler, J., Enzmann, F., Folkers, K., Bowers, C. Y., & Schally, A. V. (1969). The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide. Biochemical and Biophysical Research Communications, 37, 705–710.Google Scholar
Bourgeois, J. P., Goldmanrakic, P. S., & Rakic, P. (1994). Synaptogenesis in the prefrontal cortex of Rhesus-monkeys. Cerebral Cortex, 4, 78–96.Google Scholar
Brar, B., Sanderson, T. C., Wang, N., & Lowry, P. J. (1997). Post-translational processing of human procorticotrophin-releasing factor in transfected mouse neuroblastoma and Chinese hamster ovary cell lines. Journal of Endocrinology, 154, 431–440.Google Scholar
Burgus, R., Dunn, T. F., Desiderio, D., & Guillemin, R. (1969). Molecular structure of the hypothalamic hypophysiotropic TRF factor of ovine origin: Mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence. C.R. Comptes Rendus Hebdomadaires Des Séances De l'Academie Des Sciences, Serie D:Sciences Naturelles, 269, 1870–1873.Google Scholar
Burgus, R., Ling, N., Butcher, M., & Guillemin, R. (1973). Primary structure of somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone. Proceedings of National Academy of Sciences, 70, 684–688.Google Scholar
Buss, C., Davis, E. P., Class, Q. A., Gierczak, M., Patillo, C., Glynn, L. M., & Sandman, C. A. (2009). Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus. Early Human Development, 85, 633–638.Google Scholar
Buss, C., Davis, E. P., Shahbaba, B., Pruessner, J. C., Head, K., & Sandman, C. A. (2012). Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proceedings of the National Academy of Sciences, 109, E1312–E1319.Google Scholar
Campbell, E. A., Linton, E. A., Wolfe, C. D., Scraggs, P. R., Jones, M. T., & Lowry, P. J. (1987). Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. Journal of Clinical Endocrinology and Metabolism, 64, 1054–1059.Google Scholar
Chan, E. C., Smith, R., Lewin, T., Brinsmead, M. W., Zhang, H. P., Cubis, J., … Hurt, D. (1993). Plasma corticotropin-releasing hormone, ß-endorphin and cortisol inter-relationships during human pregnancy. Acta Endocrinologica, 128, 339–344.Google Scholar
Charil, A., Laplante, D. P., Vaillancourt, C., & King, S. (2010). Prenatal stress and brain development. Brain Research Reviews, 65, 56–79.Google Scholar
Class, Q. A., Buss, C., Davis, E. P., Gierczak, M., Pattillo, C., Chicz-DeMet, A., & Sandman, C. A. (2008). Low levels of corticotrophin-releasing hormone during early pregnancy are associated with precocious maturation of the human fetus. Developmental Neuroscience, 30, 419–426.Google Scholar
Clifton, V. L. (2010). Review: Sex and the human placenta: Mediating differential strategies of fetal growth and survival. Placenta, 31(Suppl.), S33–S39.Google Scholar
Cooperstock, M., & Campbell, J. (1996). Excess males in preterm birth: Interactions with gestational age, race, and multiple birth. Obstetrics and Gynecology, 88, 189–193.Google Scholar
Curran, M. M., Sandman, C. A., Davis, E. P., Glynn, L. M., & Baram, T. Z. (2017). Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity. PLOS ONE, 12.Google Scholar
Davis, E. P., Glynn, L. M., Dunkel-Schetter, C., Hobel, C., Chicz-DeMet, A., & Sandman, C. A. (2005). Corticotropin-releasing hormone during pregnancy is associated with infant temperament. Developmental Neuroscience, 27, 299–305.Google Scholar
Davis, E. P., & Sandman, C. A. (2010). The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Development, 81, 131–148. doi:10.1111/j.1467-8624.2009.01385.xGoogle Scholar
Davis, M., Gendelman, D. S., Tischler, M. D., & Gendelman, P. M. (1982). A primary acoustic startle circuit: Lesion and stimulation studies. Journal of Neuroscience, 2, 791–805.Google Scholar
Denver, R. J. (1997). Environmental stress as a developmental cue: Corticotropin-releasing hormone is a proximate mediator of adaptive phenotypic plasticity in amphibian metamorphosis. Hormones & Behavior, 31, 169–179.Google Scholar
Denver, R. J. (1999). Evolution of the corticotropin-releasing hormone signaling system and its role in stress-induced phenotypic plasticity. Annals of the New York Academy of Sciences, 897, 46–53.Google Scholar
Ellman, L. M., Dunkel-Schetter, C., Hobel, C. J.Chicz-DeMet, A., Glynn, L. M., & Sandman, C. A. (2008). Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturation. Developmental Psychobiology, 50, 232–241.Google Scholar
Frim, D. M., Emanuel, R. L., Robinson, B. G., Smas, C. M., Adler, G. K., & Majzoub, J. A. (1990). Characterization and gestational regulation of corticotropin-releasing hormone messenger RNA in human placenta. American Journal of Physiology, 258 (4, Pt. 1).Google Scholar
Gangestad, S. W., Caldwell Hooper, A. E., & Eaton, M. A. (2012). On the function of placental corticotropin-releasing hormone: A role in maternal-fetal conflicts over blood glucose concentrations. Biological Reviews of the Cambridge Philosophical Society, 87, 856–873.Google Scholar
Giles, W. B., McLean, M., Davies, J. J., & Smith, R. (1996). Abnormal umbilical artery Doppler waveforms and cord blood corticotropin-releasing hormone. Obstetrics and Gynecology, 87, 107–111.Google Scholar
Gluckman, P. D., Hanson, M. A., Cooper, C., & Thornburg, K. L. (2008). Effect of in utero and early-life conditions on adult health and disease. New England Journal of Medicine, 359, 61–73.Google Scholar
Glynn, L. M., Dunkel-Schetter, C., Hobel, C. J., & Sandman, C. A. (2008). Pattern of perceived stress and anxiety in pregnancy predicts preterm birth. Health Psychology, 27, 43–51. doi:10.1037/0278-6133.27.1.43Google Scholar
Glynn, L. M., & Sandman, C. A. (2014). Evaluation of the association between placental corticotrophin-releasing hormone and postpartum depressive symptoms. Psychosomatic Medicine, 76, 355–362.Google Scholar
Goland, R. S., Conwell, I. M., & Jozak, S. (1995). The effect of pre-eclampsia on human placental corticotrophin-releasing hormone content and processing. Placenta, 16, 375–382.Google Scholar
Goland, R. S., Jozak, I. S., Warren, W. B., Conwell, I. M., Stark, R. I., & Tropper, P. J. (1993). Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses. Journal of Clinical Endocrinology and Metabolism, 77, 1174–1179.Google Scholar
Goland, R. S., Wardlaw, S. L., Stark, R. I., Brown, L. S., & Frantz, A. G. (1986). High levels of corticotropin-releasing hormone immunoreactivity in maternal and fetal plasma during pregnancy. Journal of Clinical Endocrinology and Metabolism, 63, 1199–1203.Google Scholar
Grino, M., Chrusos, G. P., & Margioris, A. N. (1987). The cortiocotropin releasing hormone gene is expressed in human placenta. Biochemical and Biophysical Research Communications, 148, 1208–1214.Google Scholar
Hales, C. N., & Barker, D. J. (2001). The thrifty phenotype hypothesis. British Medical Bulletin, 60, 5–20.Google Scholar
Harris, G. W. (1937). The induction of ovulation in the rabbit by electrical stimulation of the hypothalamo–hypophysial mechanism. Proceedings of the Royal Society B, 122, 374–394.Google Scholar
Harris, G. W. (1950). Oestrous rhythm. Pseudopregnancy and the pituitary stalk in the rat. Journal of Physiology, 111, 347–360.Google Scholar
Harris, G. W. (1955). Neural control of the pituitary gland. Monographs of the Physiological Society. London, UK: Edward Arnold.Google Scholar
Harris, G. W., Manabe, Y., & Ruf, K. B. (1969). A study of the parameters of electrical stimulation of unmyelinated fibres in the pituitary stalk. Journal of Physiology, 203, 67–81.Google Scholar
Hatalski, C. G., Guorguis, C., & Baram, T. Z. (1998). Corticotropin releasing factor mRNA expression in the hypothalamic paraventricular nucleus and the central nucleus of the amygdala is modulated by repeated acute stress in the immature rat. Journal of Neuroendocrinology, 10, 663–669.Google Scholar
Howland, M. A., Sandman, C. A., Glynn, L. M., Crippen, C., & Davis, E. P. (2016). Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms. Psychoneuroendocrinology, 67, 10–17.Google Scholar
Huang, H., Xue, R., Zhang, J. Y., Ren, T., Richards, L. J., Yarowsky, P., … Mori, S. (2009). Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging. Journal of Neuroscience, 29, 4263–4273.Google Scholar
Hunt, P. A., & Hassold, T. J. (2002). Sex matters in meiosis. Science, 296, 2181–2183.Google Scholar
Kane, H. S., Dunkel-Schetter, C., Glynn, L. M., Hobel, C. J., & Sandman, C. A. (2014). Pregnancy anxiety and prenatal cortisol trajectories. Biological Psychology, 100, 13–19. doi:10.1016/j.biopsycho.2014.04.003Google Scholar
Kastin, A. J., Plotnikoff, N., Schally, A. V., & Sandman, C. A. (1976). Endocrine and central nervous system effects of hypothalamic peptides and MSH. In Ehrenpreis, S. & Kopin, I. J. (Eds.), Reviews of neuroscience (Vol. 2, pp. 111–148). New York: Raven Press.Google Scholar
King, B. R., Smith, R., & Nicholson, R. C. (2001). The regulation of human corticotrophin-releasing hormone gene expression in the placenta. Peptides, 22, 1941–1947.Google Scholar
King, B. R., Smith, R., & Nicholson, R. C. (2002). Novel glucocorticoid and cAMP interactions on the CRH gene promoter. Molecular and Cellular Endocrinology, 194, 19–28.Google Scholar
Kostovic, I., Judas, M., Rados, M., & Hrabac, P. (2002). Laminar organization of the human fetal cerebrum revealed by histochemical markers and magnetic resonance imaging. Cerebral Cortex, 12, 536–544.Google Scholar
Krulich, L., Dhariwal, A. P., & McCann, S. M. (1968). Stimulatory and inhibitory effects of purified hypothalamic extracts on growth hormone release from rat pituitary in vitro. Endocrinology, 83, 783–790.Google Scholar
Krulich, L., & McCann, S. M. (1966). Evidence for the presence of growth hormone-releasing factor in blood of hypoglycemic hypophysectomized rats. Proceedings of the Society of Experimental Biology & Medicine, 122, 668.Google Scholar
Lowry, P. J. (1993). Corticotropin-releasing factor and its binding protein in human plasma. Ciba Foundation Symposium, 172, 108–128.Google Scholar
Mains, R. E., & Eipper, B. A. (1979). Synthesis and secretion of corticotropins, melanotropins, and endorphins by rat intermediate pituitary cells. Journal of Biological Chemistry, 254, 7885–7894.Google Scholar
McCann, S. M., & Friedman, H. M. (1960). The effect of hypothalamic lesions on the secretion of luteotrophin. Endocrinology, 67, 597–608.Google Scholar
McCann, S. M., & Fruit, A. (1957). Effect of synthetic vasopressin on release of adrenocorticotrophin in rats with hypothalamic lesions. Proceedings of the Society for Experimental Biology and Medicine, 96, 566–567.Google Scholar
McLean, M., Bisits, A., Davies, J., Woods, R., Lowry, P., & Smith, R. (1995). A placental clock controlling the length of human pregnancy. Nature Medicine, 1, 460–463.Google Scholar
McMullen, S., Langley-Evans, S. C., Gambling, L., Lang, C., Swali, A., & McArdle, H. J. (2012). A common cause for a common phenotype: The gatekeeper hypothesis in fetal programming. Medical Hypotheses, 78, 88–94.Google Scholar
O'Donnell, K., O'Connor, T. G., & Glover, V. (2009). Prenatal stress and neurodevelopment of the child: Focus on the HPA axis and role of the placenta. Developmental Neuroscience, 31, 285–292.Google Scholar
Peacock, J. L., Marston, L., Marlow, N., Calvert, S. A., & Greenough, A. (2012). Neonatal and infant outcome in boys and girls born very prematurely. Pediatric Research, 71, 305–310.Google Scholar
Peña, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., … Nestler, E. (2017). Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science, 356, 1185–1188.Google Scholar
Petraglia, F., Sawchenko, P. E., Rivier, J., & Vale, W. (1987). Evidence for local stimulation of ACTH secretion by corticotrophin-releasing factor in human placenta. Nature, 328, 717–719.Google Scholar
Petraglia, F., Sutton, S., & Vale, W. (1989). Neurotransmitters and peptides modulate the release of immunoreactive corticotrophin-releasing factor from cultured human placental cells. American Journal of Obstetrics and Gynecology, 160, 247–251.Google Scholar
Pujol, R., & Lavigne-Rebillard, M. (1985). Early stages of innervation and sensory cell differentiation in the human fetal organ of Corti. Acta Oto-laryngologica, 423(Suppl.), 43–50.Google Scholar
Pujol, R., Lavigne-Rebillard, M., & Uziel, A. (1990). Physiological correlates of development of the human cochlea. Seminars in Perinatology, 14, 275–280.Google Scholar
Sanderson, T. C., Woods, R. J., Kemp, C. F., & Lowry, P. J. (2000). Detection of N-terminal pro-corticotrophin releasing hormone (CRH) and a “novel” CRH in human maternal plasma and placenta. Placenta, 21, 218–225.Google Scholar
Sandman, C. A. (2015). Fetal exposure to placental corticotropic-releasing hormone (pCRH) programs developmental trajectories. Peptides, 72, 145–153.Google Scholar
Sandman, C. A., Class, Q. A., Glynn, L. M., & Davis, E. P. (2015). Neurobehavioral disorders and Developmental Origins of Health and Disease. In Rosenfeld, C. S. (Ed.), The epigenome and developmental origins of health and disease (pp. 235–266). Waltham, MA: Academic Press/Elsevier.Google Scholar
Sandman, C. A., Curran, M. M., Davis, E. P., Glynn, L. M., Head, K., & Baram, T. Z. (2018). Cortical thinning and neuropsychiatric outcomes in children exposed to prenatal adversity: A role for placental CRH? American Journal of Psychiatry. Advance online publication. doi:10.1176/appi.ajp.2017.16121433Google Scholar
Sandman, C. A., & Davis, E. P. (2012). Neurobehavioral risk is associated with gestational exposure to stress hormones. Expert Reviews of Endocrinology & Metabolism, 7, 445–459.Google Scholar
Sandman, C. A., Davis, E. P., Buss, C., & Glynn, L. M. (2011). Prenatal programming of human neurological function. International Journal of Peptides, 2011, 837596. doi:10.1155/2011/837596Google Scholar
Sandman, C. A., Davis, E. P., Buss, C., & Glynn, L. M. (2012). Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus. Neuroendocrinology, 95, 8–21.Google Scholar
Sandman, C. A., Davis, E. P., & Glynn, L. M. (2012). Prescient human fetuses thrive. Psychological Science, 23, 93–100.Google Scholar
Sandman, C. A., Denman, P., Miller, L. H., Knott, J. R., Kastin, A. J., & Schally, A. V. (1971). Electroencephalographic measures of melanocyte-stimulating hormone. Journal of Comparative and Physiological Psychology, 76, 303–310.Google Scholar
Sandman, C. A., Glynn, L. M., & Davis, E. P. (2013). Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. Journal of Psychosomatic Research, 75, 327–335.Google Scholar
Sandman, C. A., Glynn, L. M., & Davis, E. P. (2016). Neurobehavioral consequences of fetal exposure to gestational stress. In Kisilevsk, B. S. & Reissland, N. (Eds.), Fetal development: Research on brain and behavior, environmental influences and emerging technologies (pp. 229–265). New York: Springer.Google Scholar
Sandman, C. A., Kastin, A. J., & Schally, A. V. (1969). Melanocyte-stimulating hormone and learned appetitive behavior. Experientia, 25, 1001–1002.Google Scholar
Sandman, C. A., Miller, L. H., Kastin, A. J., & Schally, A. V. (1972). A neuroendocrine influence on attention and memory. Journal of Comparative and Physiological Psychology, 80, 54–58.Google Scholar
Sandman, C., Wadhwa, P., Chicz-DeMet, A., Porto, M., & Garite, T. (1999). Maternal corticotropin-releasing hormone and habituation in the human fetus. Developmental Psychobiology, 34, 163–173.Google Scholar
Sandman, C. A., Wadhwa, P. D., Hetrick, W. P., Porto, M., & Peeke, H. V. S. (1997). Human fetal heart rate dishabituation at 32 weeks gestation. Child Development, 68, 1031–1040.Google Scholar
Sasaki, A., Shinkawa, O., Margioris, A. N., Liotta, A. S., Sato, S., Murakami, O., … Yoshinaga, K. (1987). Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery. Journal of Clinical Endocrinology and Metabolism, 64, 224–229.Google Scholar
Sasaki, A., Tempst, P., Lotta, A. S., Margioris, A. N., Hood, L. E., Kent, S. B., … Krieger, D. T. (1988). Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta. Journal of Clinical Endocrinology and Metabolism, 67, 768–773.Google Scholar
Schally, A. V., & Bowers, C. Y. (1964). Purification of luteinizing hormone-releasing factor from bovine hypothalamus. Endocrinology, 75, 608–614.Google Scholar
Selye, H. (1950). Stress. Montreal, Canada: Acta.Google Scholar
Shibasaki, T., Odagiri, E., Shizume, K., & Ling, N. (1982). Corticotropinreleasing like activity in human placenta extract. Journal of Clinical Endocrinology and Metabolism, 55, 384–386.Google Scholar
Smith, R., Mesiano, S., & McGrath, S. (2002). Hormone trajectories leading to human birth. Regulatory Peptides, 108, 159–164.Google Scholar
Smith, R., Smith, J. I., Shen, X., Engel, P. J., Bowman, M. E., McGrath, S. A., … Smith, D. W. (2009). Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor. Journal of Clinical Endocrinology and Metabolism, 94, 2066–2074.Google Scholar
Stiles, J., & Jernigan, T. L. (2010). The basics of brain development. Neuropsychological Reviews, 20, 327–348.Google Scholar
Stout, S. A., Espel, E. V., Sandman, C. A., Glynn, L. M., & Davis, E. P. (2015). Fetal programming of children's obesity risk. Psychoneuroendocrinology, 53, 29–39.Google Scholar
Takahashi, E., Folkerth, R. D., Galaburda, A. M., & Grant, P. E. (2012). Emerging cerebral connectivity in the human fetal brain: An MR tractography study, 22, 455–464.Google Scholar
Tischler, M. D., & Davis, M. (1983). A visual pathway that mediates fear-conditioned enhancement of acoustic startle. Brain Research, 276, 55–71.Google Scholar
Vale, W., Spiess, J., Rivier, C., & Rivier, J. (1981). Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and p3-endorphin. Science, 213, 1394–1397.Google Scholar
Vazquez, D. M., Bailey, C., Dent, G. W., Okimoto, D., Steffek, A., Lopez, J. F., & Levine, S. (2006). Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation. Brain Research, 1121, 83–94.Google Scholar
Voltolini, C., & Petraglia, F. (2014). Neuroendocrinology of pregnancy and parturition. In Fliers, E., Korbonits, M., & Romijn, J. A. (Eds.), Handbook of clinical neurology: Vol. 124. Clinical neuroendocrinology (pp. 17–36). Amsterdam: Elsevier.Google Scholar
Wade, N. (1981). The Nobel duel: Two scientists’ 21-year race to win the world's most coveted research prize. Garden City, NY: Anchor Press/Doubleday.Google Scholar
Wadhwa, P. D., Garite, T. J., Porto, M., Glynn, L., Chicz-DeMet, A., Dunkel-Schetter, C., & Sandman, C. A. (2004). Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth and fetal growth restriction: A prospective investigation. American Journal of Obstetrics and Gynecology, 191, 1063–1069.Google Scholar
Wolfe, C. D. A., Patel, S. P., Campbell, E. A., Anderson, J., Dornhorst, A., Lowry, P. J., & Jones, M. T. (1988). Plasma corticotrophin-releasing factor (CRF) in abnormal pregnancy. British Journal of Obstetrics and Gynecology, 95, 1003–1006.Google Scholar
Wu, M. F., Suzuki, S. S., & Siegel, J. M. (1988). Anatomical distribution and response patterns of reticular neurons active in relation to acoustic startle. Brain Research, 457, 399–406.Google Scholar
Yim, I. S, Glynn, L. M., Dunkel-Schetter, C., Hobel, C. J., Chica-DeMet, A., & Sandman, C. A. (2009). Elevated corticotrophin-releasing hormone in human pregnancy increases the risk of postpartum depressive symptoms. Archives of General Psychiatry, 66, 162–169.Google Scholar