Skip to main content
SpringerLink
Log in

Stress as a Determinant of Neurodevelopmental Outcomes

  • Chapter
  • First Online:
Neurodevelopmental Pediatrics

  • 1535 Accesses

Abstract

It is known that neurodevelopment is a dynamic process that will respond to various external stimuli. Acute maternal stress, which is reported in 15–28% of all pregnancies, can shift the neurodevelopmental trajectory resulting in altered behaviour and neuroendocrine function in offspring after birth. Notably, affected infants and children exhibit modified HPA axis function, most often showing elevated cortisol levels in both basal and stimulated states. Girls, at higher prevalence than boys, show an increased risk for affective disorder following prenatal exposure to maternal stress, while boys are more likely to exhibit symptoms of hyperactivity and reduced attention. Cognitive deficits have also been observed in association with prenatal maternal stress in both sexes, though the gestational period at which the stress occurred is critical to the nature of the outcome. In this chapter, we examine in detail the various neurologic outcomes in offspring associated with prenatal maternal stress and discuss the potential mechanisms involved. Elevated cortisol levels, placental dysfunction, and maternal immune imbalance represent possible pathways to altered fetal brain structure, neurogenesis, and synaptogenesis resulting in altered brain function and behavioural outcomes. We also discuss the growing literature around epigenetic modifications which may underlie these developmental pathways, and how maternal stress can differentially shape the developing epigenome for an altered growth trajectory.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Barker DJP. The developmental origins of adult disease. J Am Coll Nutr. 2004;23:588S–95S.

    Article  CAS  Google Scholar 

  2. Woods SM, Melville JL, Guo Y, Fan MY, Gavin A. Psychosocial stress during pregnancy. Am J Obstet Gynecol. 2010;202:61.e1–7. https://doi.org/10.1016/j.ajog.2009.07.041.

    Article  Google Scholar 

  3. Rotenberg S, McGrath JJ. Inter-relation between autonomic and HPA axis activity in children and adolescents. Biol Psychol. 2016;117:16–25.

    Article  Google Scholar 

  4. Laplante DP, et al. Stress during pregnancy affects general intellectual and language functioning in human toddlers. Pediatr Res. 2004;56:400–10. https://doi.org/10.1203/01.PDR.0000136281.34035.44.

    Article  Google Scholar 

  5. Laplante DP, Brunet A, Schmitz N, Ciampi A, King S. Project ice storm: prenatal maternal stress affects cognitive and linguistic functioning in 51/2-year-old children. J Am Acad Child Adolesc Psychiatry. 2008;47:1063–72.

    Article  Google Scholar 

  6. Andiarena A, et al. Evening salivary cortisol and alpha-amylase at 14 months and neurodevelopment at 4 years: sex differences. Horm Behav. 2017;94:135–44.

    Article  CAS  Google Scholar 

  7. Glover V, O’Donnell KJ, O’Connor TG, Fisher J. Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology - A global perspective. Dev Psychopathol. 2018;30:843–54.

    Article  Google Scholar 

  8. Hamada H, Matthews SG. Prenatal programming of stress responsiveness and behaviours: Progress and perspectives. J Neuroendocrinol. 2019;31:e12674.

    Article  Google Scholar 

  9. Sejbaek CS, et al. Maternal exposure to psychosocial job strain during pregnancy and behavioral problems in the 11-year-old children: a Danish cohort study. Eur Child Adolesc Psychiatry. 2020;30:1413–26. https://doi.org/10.1007/s00787-020-01619-z.

    Article  Google Scholar 

  10. Baibazarova E, et al. Influence of prenatal maternal stress, maternal plasma cortisol and cortisol in the amniotic fluid on birth outcomes and child temperament at 3 months. Psychoneuroendocrinology. 2013;38:907–15.

    Article  CAS  Google Scholar 

  11. Kinney DK, Munir KM, Crowley DJ, Miller AM. Prenatal stress and risk for autism. Neurosci Biobehav Rev. 2008;32:1519–32. https://doi.org/10.1016/j.neubiorev.2008.06.004.

    Article  Google Scholar 

  12. Bergman K, Sarkar P, Glover V, O’Connor TG. Quality of child-parent attachment moderates the impact of antenatal stress on child fearfulness. J Child Psychol Psychiatry Allied Discip. 2008;49:1089–98.

    Article  CAS  Google Scholar 

  13. Bergman K, Sarkar P, Glover V, O’Connor TG. Maternal prenatal cortisol and infant cognitive development: moderation by infant-mother attachment. Biol Psychiatry. 2010;67:1026–32. https://doi.org/10.1016/j.biopsych.2010.01.002.

    Article  CAS  Google Scholar 

  14. Belfort MB, et al. Breast Milk feeding, brain development, and neurocognitive outcomes: A 7-year longitudinal study in infants born at less than 30 weeks’ gestation. J Pediatr. 2016;177:133–139.e1.

    Article  Google Scholar 

  15. Brown Belfort M. The science of breastfeeding and brain development. Breastfeed Med. 2017;12:459–61.

    Article  Google Scholar 

  16. Paragliola RM, Papi G, Pontecorvi A, Corsello SM. Treatment with synthetic glucocorticoids and the hypothalamus-pituitary-adrenal axis. Int J Mol Sci. 2017;18 https://doi.org/10.3390/ijms18102201.

  17. Carpenter T, Grecian SM, Reynolds RM. Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans suggest increased vulnerability in females: A systematic review. J Dev Orig Health Dis. 2017;8:244–55. https://doi.org/10.1017/S204017441600074X.

    Article  CAS  Google Scholar 

  18. De Bruijn ATCE, Van Bakel HJA, Wijnen H, Pop VJM, Van Baar AL. Prenatal maternal emotional complaints are associated with cortisol responses in toddler and preschool aged girls. Dev Psychobiol. 2009;51:553–63. https://doi.org/10.1002/dev.20393.

    Article  CAS  Google Scholar 

  19. Yong Ping E, et al. Prenatal maternal stress predicts stress reactivity at 21/2 years of age: the Iowa flood study. Psychoneuroendocrinology. 2015;56:62–78. https://doi.org/10.1016/j.psyneuen.2015.02.015.

    Article  Google Scholar 

  20. Van Den Bergh BRH, Van Calster B, Smits T, Van Huffel S, Lagae L. Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: A prospective study on the fetal origins of depressed mood. Neuropsychopharmacology. 2008;33:536–45. https://doi.org/10.1038/sj.npp.1301450.

    Article  Google Scholar 

  21. Henry C, Kabbaj M, Simon H, Le Moal M, Maccari S. Prenatal stress increases the Hypothalamo-pituitary-adrenal Axis response in young and adult rats. J Neuroendocrinol. 1994;6:341–5. https://doi.org/10.1111/j.1365-2826.1994.tb00591.x.

    Article  CAS  Google Scholar 

  22. Kapoor A, Matthews SG. Short periods of prenatal stress affect growth, behaviour and hypothalamo-pituitary-adrenal axis activity in male Guinea pig offspring. J Physiol. 2005;566:967–77. https://doi.org/10.1113/jphysiol.2005.090191.

    Article  CAS  Google Scholar 

  23. Kapoor A, Matthews SG. Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female Guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle. Endocrinology. 2008;149:6406–15. https://doi.org/10.1210/en.2008-0347.

    Article  CAS  Google Scholar 

  24. Clarke AS, Wittwer DJ, Abbott DH, Schneider ML. Long-term effects of prenatal stress on HPA axis activity in juvenile rhesus monkeys. Dev Psychobiol. 1994;27:257–69.

    Article  CAS  Google Scholar 

  25. Tollenaar MS, Beijers R, Jansen J, Riksen-Walraven JMA, De Weerth C. Maternal prenatal stress and cortisol reactivity to stressors in human infants. Stress. 2011;14:53–65.

    Article  CAS  Google Scholar 

  26. Capron L, Glover V, Ramchandani P. Does maternal antenatal depression alter infant hypothalamic-pituitary-adrenal (HPA) axis functioning in the offspring at 4 months postpartum? Psychoneuroendocrinology. 2015;61:33.

    Article  Google Scholar 

  27. Green MK, et al. Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress. Neuroscience. 2011;192:438–51.

    Article  CAS  Google Scholar 

  28. Brunton PJ, Russell JA. Prenatal social stress in the rat programmes neuroendocrine and behavioural responses to stress in the adult offspring: sex-specific effects. J Neuroendocrinol. 2010;22:258–71.

    Article  CAS  Google Scholar 

  29. St-Cyr S, Abuaish S, Sivanathan S, McGowan PO. Maternal programming of sex-specific responses to predator odor stress in adult rats. Horm Behav. 2017;94:1–12.

    Article  Google Scholar 

  30. Danielson ML, et al. Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016. J Clin Child Adolesc Psychol. 2018;47:199–212.

    Article  Google Scholar 

  31. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). in SpringerReference (2012). doi:https://doi.org/10.1007/springerreference_179660.

  32. Lin YJ, Lo KW, Yang LK, Gau SSF. Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: comparison of life quality, functional impairment, and family function. Res Dev Disabil. 2015;47:48–60.

    Article  Google Scholar 

  33. The National Institute of Mental Health: www.nimh.nih.gov. Attention-Deficit / Hyperactivity Disorder Overview Hyperactivity-Impulsivity Risk Factors. (2019). Available at: https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml.

  34. Rodriguez A, Bohlin G. Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? J Child Psychol Psychiatry Allied Discip. 2005;46:246–54. https://doi.org/10.1111/j.1469-7610.2004.00359.x.

    Article  Google Scholar 

  35. Grizenko N, et al. Maternal stress during pregnancy, ADHD symptomatology in children and genotype: gene-environment interaction. J Can Acad Child Adolesc Psychiatry. 2012;21:9–15.

    Google Scholar 

  36. Gerardin P, et al. Depression during pregnancy: is the developmental impact earlier in boys? A prospective case-control study. J Clin Psychiatry. 2011;72:378–87. https://doi.org/10.4088/JCP.09m05724blu.

    Article  Google Scholar 

  37. Van Den Bergh BRH, Marcoen A. High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Dev. 2004;75:1085–97. https://doi.org/10.1111/j.1467-8624.2004.00727.x.

    Article  Google Scholar 

  38. Kapoor A, Matthews SG. Testosterone is involved in mediating the effects of prenatal stress in male Guinea pig offspring. J Physiol. 2011;589:755–66.

    Article  CAS  Google Scholar 

  39. Emack J, Kostaki A, Walker CD, Matthews SG. Chronic maternal stress affects growth, behaviour and hypothalamo-pituitary-adrenal function in juvenile offspring. Horm Behav. 2008;54:514–20.

    Article  CAS  Google Scholar 

  40. Emack J, Matthews SG. Effects of chronic maternal stress on hypothalamo-pituitary-adrenal (HPA) function and behavior: no reversal by environmental enrichment. Horm Behav. 2011;60:589–98.

    Article  CAS  Google Scholar 

  41. Bronson SL, Bale TL. Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal antiinflammatory treatment. Endocrinology. 2014;155:2635–46. https://doi.org/10.1210/en.2014-1040.

    Article  CAS  Google Scholar 

  42. Watson D, Clark LA. Negative affectivity: the disposition to experience aversive emotional states. Psychol Bull. 1984;96:465–90. https://doi.org/10.1037/0033-2909.96.3.465.

    Article  CAS  Google Scholar 

  43. Rubinow DR, Schmidt PJ. Sex differences and the neurobiology of affective disorders. Neuropsychopharmacology. 2019;44:111–28.

    Article  Google Scholar 

  44. Liu J, Chen X, Lewis G. Childhood internalizing behaviour: analysis and implications. J Psychiatr Ment Health Nurs. 2011;18:884–94.

    Article  CAS  Google Scholar 

  45. Demmer DH, Hooley M, Sheen J, McGillivray JA, Lum JAG. Sex differences in the prevalence of oppositional defiant disorder during middle childhood: a meta-analysis. J Abnorm Child Psychol. 2017;45:313–25.

    Article  Google Scholar 

  46. Sandman CA, Buss C, Head K, Davis EP. Fetal exposure to maternal depressive symptoms is associated with cortical thickness in late childhood. Biol Psychiatry. 2015;77:324–34. https://doi.org/10.1016/j.biopsych.2014.06.025.

    Article  Google Scholar 

  47. Swales DA, et al. Maternal depression and cortisol in pregnancy predict offspring emotional reactivity in the preschool period. Dev Psychobiol. 2018;60:557–66. https://doi.org/10.1002/dev.21631.

    Article  Google Scholar 

  48. Soe NN, et al. Pre- and post-natal maternal depressive symptoms in relation with infant frontal function, connectivity, and behaviors. PLoS One. 2016;11:e0152991. https://doi.org/10.1371/journal.pone.0152991.

    Article  CAS  Google Scholar 

  49. Sharp H, Hill J, Hellier J, Pickles A. Maternal antenatal anxiety, postnatal stroking and emotional problems in children: outcomes predicted from pre- and postnatal programming hypotheses. Psychol Med. 2015;45:269–83. https://doi.org/10.1017/S0033291714001342.

    Article  CAS  Google Scholar 

  50. Buss C, et al. Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc Natl Acad Sci. 2012;109:E1312–9. https://doi.org/10.1073/pnas.1201295109.

    Article  Google Scholar 

  51. Graham AM, et al. Maternal cortisol concentrations during pregnancy and sex-specific associations with neonatal amygdala connectivity and emerging internalizing behaviors. Biol Psychiatry. 2019;85:172–81. https://doi.org/10.1016/j.biopsych.2018.06.023.

    Article  CAS  Google Scholar 

  52. Soares-Cunha C, et al. Mild prenatal stress causes emotional and brain structural modifications in rats of both sexes. Front Behav Neurosci. 2018;12 https://doi.org/10.3389/fnbeh.2018.00129.

  53. Bennett GA, Palliser HK, Shaw JC, Walker D, Hirst JJ. Prenatal stress alters hippocampal neuroglia and increases anxiety in childhood. Dev Neurosci. 2015;37:533–45. https://doi.org/10.1159/000437302.

    Article  CAS  Google Scholar 

  54. Bennett GA, Palliser HK, Saxby B, Walker DW, Hirst JJ. Effects of prenatal stress on fetal neurodevelopment and responses to maternal neurosteroid treatment in Guinea pigs. Dev Neurosci. 2013;35:416–26. https://doi.org/10.1159/000354176.

    Article  CAS  Google Scholar 

  55. Buss C, Davis EP, Hobel CJ, Sandman CA. Maternal pregnancy-specific anxiety is associated with child executive function at 69 years age. Stress. 2011;14:665–76. https://doi.org/10.3109/10253890.2011.623250.

    Article  CAS  Google Scholar 

  56. Davis EP, Sandman CA. The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev. 2010;81:131–48. https://doi.org/10.1111/j.1467-8624.2009.01385.x.

    Article  Google Scholar 

  57. Buitelaar JK, et al. Prenatal stress and cognitive development and temperament in infants. Neurobiol Aging. 2003;24:S53–60. https://doi.org/10.1016/S0197-4580(03)00050-2.

    Article  Google Scholar 

  58. DiPietro JA, Novak MFSX, Costigan KA, Atella LD, Reusing SP. Maternal psychological distress during pregnancy in relation to child development at age two. Child Dev. 2006;77:573–87. https://doi.org/10.1111/j.1467-8624.2006.00891.x.

    Article  Google Scholar 

  59. Sun H, et al. Prenatal stress impairs spatial learning and memory associated with lower mRNA level of the CAMKII and CREB in the adult female rat hippocampus. Neurochem Res. 2017;42:1496–503. https://doi.org/10.1007/s11064-017-2206-z.

    Article  CAS  Google Scholar 

  60. Yang J, Han H, Cao J, Li L, Xu L. Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring. Hippocampus. 2006;16:431–6. https://doi.org/10.1002/hipo.20181.

    Article  Google Scholar 

  61. de los Angeles GAM, del Carmen ROM, Wendy PM, Socorro RM. Tactile stimulation effects on hippocampal neurogenesis and spatial learning and memory in prenatally stressed rats. Brain Res Bull. 2016;124:1–11. https://doi.org/10.1016/j.brainresbull.2016.03.003.

    Article  Google Scholar 

  62. de los Angeles GAM, del Carmen ROM, Arzate SG, Retana-Márquez S. Prenatal stress reduces learning and memory in pre-pubertal, young, and adult rats of both sexes. Glob J Zool. 2017;2:013–20.

    Article  Google Scholar 

  63. Sofiabadi M, et al. Effects of prenatal combined stress on passive avoidance learning and memory in rats. Neurophysiology. 2018;50:116–23.

    Article  Google Scholar 

  64. Modir F, Elahdadi Salmani M, Goudarzi I, Lashkarboluki T, Abrari K. Prenatal stress decreases spatial learning and memory retrieval of the adult male offspring of rats. Physiol Behav. 2014;129:104–9. https://doi.org/10.1016/j.physbeh.2014.02.040.

    Article  CAS  Google Scholar 

  65. Son GH. Maternal stress produces learning deficits associated with impairment of NMDA receptor-mediated synaptic plasticity. J Neurosci. 2006;26:3309–18. https://doi.org/10.1523/jneurosci.3850-05.2006.

    Article  CAS  Google Scholar 

  66. Setiawan E, Jackson MF, Macdonald JF, Matthews SG. Effects of repeated prenatal glucocorticoid exposure on long-term potentiation in the juvenile Guinea-pig hippocampus. J Physiol. 2007;581:1033–42. https://doi.org/10.1113/jphysiol.2006.127381.

    Article  CAS  Google Scholar 

  67. Pickering C, Gustafsson L, Cebere A, Nylander I, Liljequist S. Repeated maternal separation of male Wistar rats alters glutamate receptor expression in the hippocampus but not the prefrontal cortex. Brain Res. 2006;1099:101–8. https://doi.org/10.1016/j.brainres.2006.04.136.

    Article  CAS  Google Scholar 

  68. Roceri M, Hendriks W, Racagni G, Ellenbroek BA, Riva MA. Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Mol Psychiatry. 2002;7:609–16. https://doi.org/10.1038/sj.mp.4001036.

    Article  CAS  Google Scholar 

  69. Meunier J, Gué M, Récasens M, Maurice T. Attenuation by a sigma 1 (σ 1) receptor agonist of the learning and memory deficits induced by a prenatal restraint stress in juvenile rats. Br J Pharmacol. 2004;142:689–700. https://doi.org/10.1038/sj.bjp.0705835.

    Article  CAS  Google Scholar 

  70. Su T-P, Hayashi T. Understanding the molecular mechanism of Sigma-1 receptors: towards A hypothesis that Sigma-1 receptors are intracellular amplifiers for signal transduction. Curr Med Chem. 2005;10:2073–80. https://doi.org/10.2174/0929867033456783.

    Article  Google Scholar 

  71. Lemaire V, Koehl M, Le Moal M, Abrous DN. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA. 2000;97:11032–7.

    Article  CAS  Google Scholar 

  72. Darnaudéry M, Maccari S. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008;57:571–85. https://doi.org/10.1016/j.brainresrev.2007.11.004.

    Article  CAS  Google Scholar 

  73. Moors M, et al. Dickkopf 1 mediates glucocorticoid-induced changes in human neural progenitor cell proliferation and differentiation. Toxicol Sci. 2012;125:488–95. https://doi.org/10.1093/toxsci/kfr304.

    Article  CAS  Google Scholar 

  74. Li J, et al. Late gestational maternal serum cortisol is inversely associated with fetal brain growth. Neurosci Biobehav Rev. 2012;36:1085–92. https://doi.org/10.1016/j.neubiorev.2011.12.006.

    Article  CAS  Google Scholar 

  75. Jones SL, et al. Larger amygdala volume mediates the association between prenatal maternal stress and higher levels of externalizing behaviors: sex specific effects in project ice storm. Front Hum Neurosci. 2019;13 https://doi.org/10.3389/fnhum.2019.00144.

  76. Mehta MA, et al. Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian adoptees study pilot. J Child Psychol Psychiatry. 2009;50:943–51. https://doi.org/10.1111/j.1469-7610.2009.02084.x.

    Article  Google Scholar 

  77. Favaro A, Tenconi E, Degortes D, Manara R, Santonastaso P. Neural correlates of prenatal stress in young women. Psychol Med. 2015;45:2533–43. https://doi.org/10.1017/S003329171500046X.

    Article  CAS  Google Scholar 

  78. Buss C, et al. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus. Early Hum Dev. 2009;85:633–8. https://doi.org/10.1016/j.earlhumdev.2009.08.001.

    Article  Google Scholar 

  79. Nathanielsz PW, et al. Life before birth: effects of cortisol on future cardiovascular and metabolic function. Acta Paediatrica Int J Paediatr. 2003;92:766–72. https://doi.org/10.1080/08035250310003668.

    Article  CAS  Google Scholar 

  80. Kim DJ, et al. Prenatal maternal cortisol has sex-specific associations with child brain network properties. Cereb Cortex. 2017;27:5230–41. https://doi.org/10.1093/cercor/bhw303.

    Article  Google Scholar 

  81. Van Den Bergh BRH, Dahnke R, Mennes M. Prenatal stress and the developing brain: risks for neurodevelopmental disorders - ERRATUM. Dev Psychopathol. 2018;31:395. https://doi.org/10.1017/S0954579418001402.

    Article  Google Scholar 

  82. Soe NN, et al. Perinatal maternal depressive symptoms alter amygdala functional connectivity in girls. Hum Brain Mapp. 2018;39:680–90. https://doi.org/10.1002/hbm.23873.

    Article  Google Scholar 

  83. Kang HJ, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478:483–9. https://doi.org/10.1038/nature10523.

    Article  CAS  Google Scholar 

  84. Salm AK, et al. Lateral amygdaloid nucleus expansion in adult rats is associated with exposure to prenatal stress. Dev Brain Res. 2004;148:159–67. https://doi.org/10.1016/j.devbrainres.2003.11.005.

    Article  CAS  Google Scholar 

  85. Sarabdjitsingh RA, Loi M, Joëls M, Dijkhuizen RM, Van Der Toorn A. Early life stress-induced alterations in rat brain structures measured with high resolution MRI. PLoS One. 2017;12:e0185061. https://doi.org/10.1371/journal.pone.0185061.

    Article  CAS  Google Scholar 

  86. Coe CL, et al. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biol Psychiatry. 2003;54:1025–34. https://doi.org/10.1016/S0006-3223(03)00698-X.

    Article  CAS  Google Scholar 

  87. Jia N, et al. Prenatal stress causes dendritic atrophy of pyramidal neurons in hippocampal CA3 region by glutamate in offspring rats. Dev Neurobiol. 2010; https://doi.org/10.1002/dneu.20766.

  88. Behan ÁT, et al. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress. Eur Neuropsychopharmacol. 2011;21:71–9. https://doi.org/10.1016/j.euroneuro.2010.07.004.

    Article  CAS  Google Scholar 

  89. Martínez-Téllez RI, Hernández-Torres E, Gamboa C, Flores G. Prenatal stress alters spine density and dendritic length of nucleus accumbens and hippocampus neurons in rat offspring. Synapse. 2009;63:794–804. https://doi.org/10.1002/syn.20664.

    Article  CAS  Google Scholar 

  90. Hosseini-Sharifabad M, Hadinedoushan H. Prenatal stress induces learning deficits and is associated with a decrease in granules and CA3 cell dendritic tree size in rat hippocampus. Anat Sci Int. 2007;82:211–7. https://doi.org/10.1111/j.1447-073X.2007.00186.x.

    Article  Google Scholar 

  91. Lussier SJ, Stevens HE. Delays in GABAergic interneuron development and behavioral inhibition after prenatal stress. Dev Neurobiol. 2016;76:1078–91. https://doi.org/10.1002/dneu.22376.

    Article  CAS  Google Scholar 

  92. Zhang H, Shang Y, Xiao X, Yu M, Zhang T. Prenatal stress-induced impairments of cognitive flexibility and bidirectional synaptic plasticity are possibly associated with autophagy in adolescent male-offspring. Exp Neurol. 2017;298:68–78. https://doi.org/10.1016/j.expneurol.2017.09.001.

    Article  Google Scholar 

  93. Bonnin A, et al. A transient placental source of serotonin for the fetal forebrain. Nature. 2011;472:347–50. https://doi.org/10.1038/nature09972.

    Article  CAS  Google Scholar 

  94. Bonnin A, Torii M, Wang L, Rakic P, Levitt P. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci. 2007;10:588–97. https://doi.org/10.1038/nn1896.

    Article  CAS  Google Scholar 

  95. Bonnin A, Peng W, Hewlett W, Levitt P. Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience. 2006;141:781–94. https://doi.org/10.1016/j.neuroscience.2006.04.036.

    Article  CAS  Google Scholar 

  96. Paquette AG, Marsit CJ. The developmental basis of epigenetic regulation of HTR2A and psychiatric outcomes. J Cell Biochem. 2014;115:2065–72. https://doi.org/10.1002/jcb.24883.

    Article  CAS  Google Scholar 

  97. Goeden N, et al. Maternal inflammation disrupts fetal neurodevelopment via increased placental output of serotonin to the fetal brain. J Neurosci. 2016;36:6041–9. https://doi.org/10.1523/jneurosci.2534-15.2016.

    Article  CAS  Google Scholar 

  98. Peters DAV. Effects of maternal stress during different gestational periods on the serotonergic system in adult rat offspring. Pharmacol Biochem Behav. 1988;31:839–43. https://doi.org/10.1016/0091-3057(88)90393-0.

    Article  CAS  Google Scholar 

  99. Peters DAV. Both prenatal and postnatal factors contribute to the effects of maternal stress on offspring behavior and central 5-hydroxytryptamine receptors in the rat. Pharmacol Biochem Behav. 1988;30:669–73. https://doi.org/10.1016/0091-3057(88)90081-0.

    Article  CAS  Google Scholar 

  100. Peters DAV. Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxytryptamine synthesis in rats: A possible mechanism by which stress influences brain development. Pharmacol Biochem Behav. 1990;35:943–7. https://doi.org/10.1016/0091-3057(90)90383-S.

    Article  CAS  Google Scholar 

  101. Meaney MJ, et al. Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin. J Neurosci. 2000;20:3926–35.

    Article  CAS  Google Scholar 

  102. Mitchell JB, Rowe W, Boksa P, Meaney MJ. Serotonin regulates type II corticosteroid receptor binding in hippocampal cell cultures. J Neurosci. 1990;10:1745–52.

    Article  CAS  Google Scholar 

  103. Erdeljan P, MacDonald JF, Matthews SG. Glucocorticoids and serotonin alter glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR) mRNA levels in fetal mouse hippocampal neurons, in vitro. Brain Res. 2001;896:130–6. https://doi.org/10.1016/S0006-8993(01)02075-3.

    Article  CAS  Google Scholar 

  104. Yeager MP, et al. In vivo exposure to high or low cortisol has biphasic effects on inflammatory response pathways of human monocytes. Anesth Analg. 2008;107:1726–34. https://doi.org/10.1213/ane.0b013e3181875fb0.

    Article  CAS  Google Scholar 

  105. Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med. 2014;76:181–9. https://doi.org/10.1097/PSY.0000000000000049.

    Article  Google Scholar 

  106. Calcia MA, et al. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 2016;233:1637–50. https://doi.org/10.1007/s00213-016-4218-9.

    Article  CAS  Google Scholar 

  107. Zen M, et al. The kaleidoscope of glucorticoid effects on immune system. Autoimmun Rev. 2011;10:305–10. https://doi.org/10.1016/j.autrev.2010.11.009.

    Article  CAS  Google Scholar 

  108. Hantsoo L, Kornfield S, Anguera MC, Epperson CN. Inflammation: A proposed intermediary between maternal stress and offspring neuropsychiatric risk. Biol Psychiatry. 2019;85:97–106. https://doi.org/10.1016/j.biopsych.2018.08.018.

    Article  Google Scholar 

  109. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Psiquiatria Biologica. 2010;17:71–80. https://doi.org/10.1016/j.psiq.2010.04.001.

    Article  Google Scholar 

  110. Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: A review and meta-analysis. Brain Behav Immun. 2007;21:901–12. https://doi.org/10.1016/j.bbi.2007.03.011.

    Article  CAS  Google Scholar 

  111. Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci. 2007;104:1319–24. https://doi.org/10.1073/pnas.0610362104.

    Article  CAS  Google Scholar 

  112. Christian LM, Franco A, Glaser R, Iams JD. Depressive symptoms are associated with elevated serum proinflammatory cytokines among pregnant women. Brain Behav Immun. 2009;23:750–4. https://doi.org/10.1016/j.bbi.2009.02.012.

    Article  CAS  Google Scholar 

  113. Shelton MM, Schminkey DL, Groer MW. Relationships among prenatal depression, plasma cortisol, and inflammatory cytokines. Biol Res Nurs. 2015;17:295–302. https://doi.org/10.1177/1099800414543821.

    Article  CAS  Google Scholar 

  114. Coussons-Read ME, Okun ML, Nettles CD. Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy. Brain Behav Immun. 2007;21:343–50. https://doi.org/10.1016/j.bbi.2006.08.006.

    Article  CAS  Google Scholar 

  115. Gur TL, et al. Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring. Brain Behav Immun. 2017;64:50–8. https://doi.org/10.1016/j.bbi.2016.12.021.

    Article  CAS  Google Scholar 

  116. Tong L, et al. Brain-derived neurotrophic factor-dependent synaptic plasticity is suppressed by Interleukin-1 via p38 mitogen-activated protein kinase. J Neurosci. 2012;32:17714–24. https://doi.org/10.1523/JNEUROSCI.1253-12.2012.

    Article  CAS  Google Scholar 

  117. Krishnan V, Nestler EJ. Linking molecules to mood: new insight into the biology of depression. Am J Psychiatr. 2010;167:1305–20. https://doi.org/10.1176/appi.ajp.2009.10030434.

    Article  Google Scholar 

  118. Beitins IZ, Bayard F, Ances IG, Kowarski A, Migeon CJ. The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term. Pediatr Res. 1973;7:509–19. https://doi.org/10.1203/00006450-197305000-00004.

    Article  CAS  Google Scholar 

  119. Dahlerup BR, et al. Maternal stress and placental function, a study using questionnaires and biomarkers at birth. PLoS One. 2018;13:e0207184. https://doi.org/10.1371/journal.pone.0207184.

    Article  CAS  Google Scholar 

  120. Wieczorek A, et al. Sex-specific regulation of stress-induced fetal glucocorticoid surge by the mouse placenta. Am J Physiol Metab. 2019;317:E109–20. https://doi.org/10.1152/ajpendo.00551.2018.

    Article  CAS  Google Scholar 

  121. O’Donnell KJ, et al. Maternal prenatal anxiety and downregulation of placental 11β-HSD2. Psychoneuroendocrinology. 2012;37:818–26.

    Article  Google Scholar 

  122. Seth S, Lewis AJ, Saffery R, Lappas M, Galbally M. Maternal prenatal mental health and placental 11β-HSD2 gene expression: initial findings from the mercy pregnancy and emotionalwellbeing study. Int J Mol Sci. 2015;16:27482–96. https://doi.org/10.3390/ijms161126034.

    Article  CAS  Google Scholar 

  123. Peña CJ, Monk C, Champagne FA. Epigenetic effects of prenatal stress on 11β-Hydroxysteroid Dehydrogenase-2 in the placenta and fetal brain. PLoS One. 2012;7 https://doi.org/10.1371/journal.pone.0039791.

  124. Mairesse J, et al. Maternal stress alters endocrine function of the feto-placental unit in rats. Am J Physiol Metab. 2007;292:E1526–33. https://doi.org/10.1152/ajpendo.00574.2006.

    Article  CAS  Google Scholar 

  125. Mina TH, Räikkönen K, Riley SC, Norman JE, Reynolds RM. Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: role of obesity and sex. Psychoneuroendocrinology. 2015;59:112–22. https://doi.org/10.1016/j.psyneuen.2015.05.004.

    Article  CAS  Google Scholar 

  126. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23:781–3. https://doi.org/10.1101/gad.1787609.

    Article  CAS  Google Scholar 

  127. Saitou M, Kagiwada S, Kurimoto K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development. 2012;139:15–31. https://doi.org/10.1242/dev.050849.

    Article  CAS  Google Scholar 

  128. Schraut KG, et al. Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice. Transl Psychiatry. 2014;4:e473. https://doi.org/10.1038/tp.2014.107.

    Article  CAS  Google Scholar 

  129. Crudo A, et al. Glucocorticoid programming of the fetal male hippocampal epigenome. Endocrinology. 2013;154:1168–80.

    Article  CAS  Google Scholar 

  130. Crudo A, et al. Effects of antenatal synthetic glucocorticoid on glucocorticoid receptor binding, DNA methylation, and genome-wide mRNA levels in the fetal male hippocampus. Endocrinology. 2013;154:4170–81.

    Article  CAS  Google Scholar 

  131. Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008;28:9055–65. https://doi.org/10.1523/JNEUROSCI.1424-08.2008.

    Article  CAS  Google Scholar 

  132. Weaver ICG, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7:847–54. https://doi.org/10.1038/nn1276.

    Article  CAS  Google Scholar 

  133. Lee RS, et al. Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice. Endocrinology. 2010;151:4332–43. https://doi.org/10.1210/en.2010-0225.

    Article  CAS  Google Scholar 

  134. Ewald ER, et al. Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure. Psychoneuroendocrinology. 2014;44:112–22. https://doi.org/10.1016/j.psyneuen.2014.03.003.

    Article  CAS  Google Scholar 

  135. Yang X, et al. Biochemical and biophysical research communications glucocorticoid-induced loss of DNA methylation in non-neuronal cells and potential involvement of DNMT1 in epigenetic regulation of Fkbp5. Biochem Biophys Res Commun. 2012;420:570–5.

    Article  CAS  Google Scholar 

  136. Zheng Y, Fan W, Zhang X, Dong E. Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus. Epigenetics. 2016;11:150–62. https://doi.org/10.1080/15592294.2016.1146850.

    Article  Google Scholar 

  137. Dong E, et al. Brain-derived neurotrophic factor epigenetic modifications associated with schizophrenia-like phenotype induced by prenatal stress in mice. Biol Psychiatry. 2015;77:589–96. https://doi.org/10.1016/j.biopsych.2014.08.012.

    Article  CAS  Google Scholar 

  138. Boersma GJ, et al. Prenatal stress decreases Bdnf expression and increases methylation of Bdnf exon IV in rats. Epigenetics. 2013;9:437–47. https://doi.org/10.4161/epi.27558.

    Article  Google Scholar 

  139. Branchi I. The mouse communal nest: investigating the epigenetic influences of the early social environment on brain and behavior development. Neurosci Biobehav Rev. 2009;33:551–9. https://doi.org/10.1016/j.neubiorev.2008.03.011.

    Article  Google Scholar 

  140. Nair A, et al. Stressor-specific regulation of distinct brain-derived neurotrophic factor transcripts and cyclic AMP response element-binding protein expression in the postnatal and adult rat hippocampus. Neuropsychopharmacology. 2007;32:1504–19. https://doi.org/10.1038/sj.npp.1301276.

    Article  CAS  Google Scholar 

  141. Roth TL, Zoladz PR, Sweatt JD, Diamond DM. Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder. J Psychiatr Res. 2011;45:919–26. https://doi.org/10.1016/j.jpsychires.2011.01.013.

    Article  Google Scholar 

  142. St-Cyr S, McGowan PO. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor. Front Behav Neurosci. 2015;9 https://doi.org/10.3389/fnbeh.2015.00145.

  143. Kumamaru E, et al. Glucocorticoid prevents brain-derived neurotrophic factor-mediated maturation of synaptic function in developing hippocampal neurons through reduction in the activity of mitogen-activated protein kinase. Mol Endocrinol. 2008;22:546–58. https://doi.org/10.1210/me.2007-0264.

    Article  CAS  Google Scholar 

  144. Neeley EW, Berger R, Koenig JI, Leonard S. Strain dependent effects of prenatal stress on gene expression in the rat hippocampus. Physiol Behav. 2011;104:334–9. https://doi.org/10.1016/j.physbeh.2011.02.032.

    Article  CAS  Google Scholar 

  145. Matrisciano F, et al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology. 2013;68:184–94. https://doi.org/10.1016/j.neuropharm.2012.04.013.

    Article  CAS  Google Scholar 

  146. Roth TL, Lubin FD, Funk AJ, Sweatt JD. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009;65:760–9. https://doi.org/10.1016/j.biopsych.2008.11.028.

    Article  CAS  Google Scholar 

  147. Howerton CL, Morgan CP, Fischer DB, Bale TL. O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. Proc Natl Acad Sci U S A. 2013;110:5169–74. https://doi.org/10.1073/pnas.1300065110.

    Article  Google Scholar 

  148. Howerton CL, Bale TL. Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction. Proc Natl Acad Sci U S A. 2014;111:9639–44. https://doi.org/10.1073/pnas.1401203111.

    Article  CAS  Google Scholar 

  149. Nugent BM, O’Donnell CM, Epperson CN, Bale TL. Placental H3K27me3 establishes female resilience to prenatal insults. Nat Commun. 2018;9:2555. https://doi.org/10.1038/s41467-018-04992-1.

    Article  CAS  Google Scholar 

  150. Yehuda R, et al. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in holocaust survivor offspring. Am J Psychiatry. 2014;171:872–80. https://doi.org/10.1176/appi.ajp.2014.13121571.

    Article  Google Scholar 

  151. Lehrner A, et al. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of holocaust survivors. Psychoneuroendocrinology. 2014;40:213–20. https://doi.org/10.1016/j.psyneuen.2013.11.019.

    Article  CAS  Google Scholar 

  152. Morgan CP, Bale TL. Early prenatal stress epigenetically programs dysmasculinization in second-generation offspring via the paternal lineage. J Neurosci. 2011;31:11748–55. https://doi.org/10.1523/JNEUROSCI.1887-11.2011.

    Article  CAS  Google Scholar 

  153. Rodgers AB, Morgan CP, Bronson SL, Revello S, Bale TL. Paternal stress exposure alters sperm MicroRNA content and reprograms offspring HPA stress axis regulation. J Neurosci. 2013;33:9003–12. https://doi.org/10.1523/JNEUROSCI.0914-13.2013.

    Article  CAS  Google Scholar 

  154. Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Neurosci: Dialogues Clin; 2011.

    Google Scholar 

  155. Franklin TB, et al. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry. 2010;68:408–15. https://doi.org/10.1016/j.biopsych.2010.05.036.

    Article  Google Scholar 

  156. Rodgers AB, Morgan CP, Leu NA, Bale TL. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc Natl Acad Sci U S A. 2015;112:13699–704. https://doi.org/10.1073/pnas.1508347112.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Sinai Health System/University of Toronto, Toronto, ON, Canada

    Bona Kim

  2. Department of Physiology, University of Toronto, Toronto, ON, Canada

    Stephen G. Matthews

Authors
  1. Bona Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen G. Matthews
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bona Kim .

Editor information

Editors and Affiliations

  1. Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia

    David D. Eisenstat

  2. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

    Dan Goldowitz

  3. Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    Tim F. Oberlander

  4. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Jerome Y. Yager

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Crown

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kim, B., Matthews, S.G. (2023). Stress as a Determinant of Neurodevelopmental Outcomes. In: Eisenstat, D.D., Goldowitz, D., Oberlander, T.F., Yager, J.Y. (eds) Neurodevelopmental Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-031-20792-1_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-20792-1_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-20791-4

  • Online ISBN: 978-3-031-20792-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation