Current Psychiatry Reports

, 21:99 | Cite as

Prenatal Maternal Stress and the Cascade of Risk to Schizophrenia Spectrum Disorders in Offspring

  • Emily Lipner
  • Shannon K. Murphy
  • Lauren M. EllmanEmail author
Reproductive Psychiatry and Women's Health (CN Epperson and L Hantsoo, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Reproductive Psychiatry and Women's Health


Purpose of Review

Disruptions in fetal development (via genetic and environmental pathways) have been consistently associated with risk for schizophrenia in a variety of studies. Although multiple obstetric complications (OCs) have been linked to schizophrenia, this review will discuss emerging evidence supporting the role of prenatal maternal stress (PNMS) in the etiology of schizophrenia spectrum disorders (SSD). In addition, findings linking PNMS to intermediate phenotypes of the disorder, such as OCs and premorbid cognitive, behavioral, and motor deficits, will be reviewed. Maternal immune and endocrine dysregulation will also be explored as potential mechanisms by which PNMS confers risk for SSD.

Recent Findings

PNMS has been linked to offspring SSD; however, findings are mixed due to inconsistent and retrospective assessments of PNMS and lack of specificity about SSD outcomes. PNMS is also associated with various intermediate phenotypes of SSD (e.g., prenatal infection/inflammation, decreased fetal growth, hypoxia-related OCs). Recent studies continue to elucidate the impact of PNMS while considering the moderating roles of fetal sex and stress timing, but it is still unclear which aspects of PNMS (e.g., type, timing) confer risk for SSD specifically.


PNMS increases risk for SSD, but only in a small portion of fetuses exposed to PNMS. Fetal sex, genetics, and other environmental factors, as well as additional pre- and postnatal insults, likely contribute to the PNMS-SSD association. Longitudinal birth cohort studies are needed to prospectively illuminate the mechanisms that account for the variability in outcomes following PNMS.


Prenatal stress Obstetric complications Maternal inflammation Premorbid deficits Schizophrenia 



We would like to thank Seth Maxwell for his helpful edits.

Funding Information

This review was supported by the National Institute of Mental Health Grants MH096478 and MH118545 awarded to Lauren Ellman.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Seidman LJ, Mirsky AF. Evolving notions of schizophrenia as a developmental neurocognitive disorder. J Int Neuropsychol Soc. 2017;23:881–92.PubMedCrossRefGoogle Scholar
  2. 2.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-V). 5th ed. Washington: American Psychological Association; 2013.CrossRefGoogle Scholar
  3. 3.
    Nuechterlein KH, Dawson ME. A heuristic vulnerability/stress model of schizophrenic episodes. Schizophr Bull. 1984;10:300–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Aleman A, Kahn RS, Selten J-P. Sex differences in the risk of schizophrenia: evidence from meta-analysis. Arch Gen Psychiatry. 2003;60:565–71.PubMedCrossRefGoogle Scholar
  5. 5.
    McGrath JJ, Susser ES. New directions in the epidemiology of schizophrenia. Med J Aust. 2009;190:S7–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Cannon TD, Kaprio J, Lönnqvist J, Huttunen M, Koskenvuo M. The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Arch Gen Psychiatry. 1998;55:67–74.PubMedCrossRefGoogle Scholar
  7. 7.
    • Iampietro MC, Ellman LM. Maternal stress during pregnancy and schizophrenia. In: Brown AS, Patterson PH, editors. The origins of schizophrenia. New York: Columbia University Press; 2012. p. 120–39. Comprehensive book chapter examining the specific relationship between PNMS and risk for SSD with research through about 2012.Google Scholar
  8. 8.
    Mittal VA, Ellman LM, Cannon TD. Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications. Schizophr Bull. 2008;34:1083–94.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: historical and meta-analytic review. AJP. 2002;159:1080–92.CrossRefGoogle Scholar
  10. 10.
    • Fineberg AM, Ellman LM. Inflammatory cytokines and neurological and neurocognitive alterations in the course of schizophrenia. Biol Psychiatry. 2013;73:951–66. This article comprehensively reviews human research focused on the role of inflammation in the developmental life course for schizophrenia, from the prenatal period to fully-formed psychosis.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    •• Ellman LM, Murphy SK, Maxwell SD. Pre- and perinatal risk factors for serious mental disorders: ethical considerations in prevention and prediction efforts. J Ethics Mental Health. 2018;10:1–14. This paper discusses ethical consideration in research examining obstetric complications and mental health outcomes, including discussion of how a cascade model framework could better inform prevention, prediction and intervention efforts for offspring psychopathology.Google Scholar
  12. 12.
    Malaspina D, Corcoran C, Kleinhaus KR, Perrin MC, Fennig S, Nahon D, et al. Acute maternal stress in pregnancy and schizophrenia in offspring: a cohort prospective study. BMC Psychiatry. 2008;8:71.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Van Os J, Selten J-P. Prenatal exposure to maternal stress and subsequent schizophrenia. Br J Psychiatry. 1998;172:324–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Roseboom TJ, Painter RC, van Abeelen AFM, Veenendaal MVE, de Rooij SR. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas. 2011;70:141–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Song S, Wang W, Hu P. Famine, death, and madness: schizophrenia in early adulthood after prenatal exposure to the Chinese Great Leap Forward Famine. Soc Sci Med. 2009;68:1315–21.PubMedCrossRefGoogle Scholar
  16. 16.
    Selten JP, van der Graaf Y, van Duursen R, Gispen-de Wied CC, Kahn RS. Psychotic illness after prenatal exposure to the 1953 Dutch Flood Disaster. Schizophr Res. 1999;35:243–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Huttunen MO, Niskanen P. Prenatal loss of father and psychiatric disorders. Arch Gen Psychiatry. 1978;35:429–31.PubMedCrossRefGoogle Scholar
  18. 18.
    Khashan AS, Abel KM, McNamee R, Pedersen MG, Webb RT, Baker PN, et al. Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Arch Gen Psychiatry. 2008;65:146–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Abel KM, Heuvelman HP, Jörgensen L, Magnusson C, Wicks S, Susser E, et al. Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study. BMJ. 2014;348:f7679.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Class QA, Abel KM, Khashan AS, Rickert ME, Dalman C, Larsson H, et al. Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress. Psychol Med. 2014;44:71–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Levine SZ, Levav I, Goldberg Y, Pugachova I, Becher Y, Yoffe R. Exposure to genocide and the risk of schizophrenia: a population-based study. Psychol Med. 2016;46:855–63.PubMedCrossRefGoogle Scholar
  22. 22.
    Levine SZ, Levav I, Yoffe R, Pugachova I. The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia. Schizophr Res. 2014;158:236–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Levine SZ, Levav I, Pugachova I, Yoffe R, Becher Y. Transgenerational effects of genocide exposure on the risk and course of schizophrenia: a population-based study. Schizophr Res. 2016;176:540–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Weinstein Y, Levav I, Gelkopf M, Roe D, Yoffe R, Pugachova I, et al. Association of maternal exposure to terror attacks during pregnancy and the risk of schizophrenia in the offspring: a population-based study. Schizophr Res. 2018;199:163–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Susser E, Neugebauer R, Hoek HW, Brown AS, Lin S, Labovitz D, et al. Schizophrenia after prenatal famine: further evidence. Arch Gen Psychiatry. 1996;53:25–31.PubMedCrossRefGoogle Scholar
  26. 26.
    Xu M-Q, Sun W-S, Liu B-X, Feng G-Y, Yu L, Yang L, et al. Prenatal malnutrition and adult schizophrenia: further evidence from the 1959-1961 Chinese famine. Schizophr Bull. 2009;35:568–76.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Sioen I, Den Hond E, Nelen V, Van de Mieroop E, Croes K, Van Larebeke N, et al. Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years. Environ Int. 2013;59:225–31.PubMedCrossRefGoogle Scholar
  28. 28.
    Attademo L, Bernardini F, Garinella R, Compton MT. Environmental pollution and risk of psychotic disorders: a review of the science to date. Schizophr Res. 2017;181:55–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Hantsoo L, Jašarević E, Criniti S, McGeehan B, Tanes C, Sammel MD, et al. Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy. Brain Behav Immun. 2019;75:240–50.PubMedCrossRefGoogle Scholar
  30. 30.
    Myhrman A, Rantakallio P, Isohanni M, Jones P, Partanen U. Unwantedness of a pregnancy and schizophrenia in the child. Br J Psychiatry. 1996;169:637–40.PubMedCrossRefGoogle Scholar
  31. 31.
    McNeil TF, Schubert EW, Cantor-Graae E, Brossner M, Schubert P, Henriksson KM. Unwanted pregnancy as a risk factor for offspring schizophrenia-spectrum and affective disorders in adulthood: a prospective high-risk study. Psychol Med. 2009;39:957–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Herman DB, Brown AS, Opler MG, Desai M, Malaspina D, Bresnahan M, et al. Does unwantedness of pregnancy predict schizophrenia in the offspring? Findings from a prospective birth cohort study. Soc Psychiatry Psychiatr Epidemiol. 2006;41:605–10.PubMedCrossRefGoogle Scholar
  33. 33.
    •• Fineberg AM, Ellman LM, Schaefer CA, Maxwell SD, Shen L, Chaudhury HN, et al. Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: differential influences of fetal sex. Psychiatry Res. 2016;236:91–7. This study provides evidence from a prospective birth cohort study that subjective stress is associated with schizophrenia risk in offspring in a sex-dependent manner.PubMedCrossRefGoogle Scholar
  34. 34.
    • Brannigan R, Cannon M, Tanskanen A, Huttunen MO, Leacy FP, Clarke MC. The association between subjective maternal stress during pregnancy and offspring clinically diagnosed psychiatric disorders. Acta Psychiatr Scand. 2019;139:304–10. One of the most recent studies examining the link between prospectively collected stress measures and risk for psychiatric disorders in offspring with a large sample from a national registry.PubMedCrossRefGoogle Scholar
  35. 35.
    Dorrington S, Zammit S, Asher L, Evans J, Heron J, Lewis G. Perinatal maternal life events and psychotic experiences in children at twelve years in a birth cohort study. Schizophr Res. 2014;152:158–63.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Pugliese V, Bruni A, Carbone EA, Calabrò G, Cerminara G, Sampogna G, et al. Maternal stress, prenatal medical illnesses and obstetric complications: risk factors for schizophrenia spectrum disorder, bipolar disorder and major depressive disorder. Psychiatry Res. 2019;271:23–30.PubMedCrossRefGoogle Scholar
  37. 37.
    Wadhwa PD, Entringer S, Buss C, Lu MC. The contribution of maternal stress to preterm birth: issues and considerations. Clin Perinatol. 2011;38:351–84.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Brown AS. Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol. 2012;72:1272–6.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Khandaker GM, Zimbron J, Lewis G, Jones PB. Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychol Med. 2013;43:239–57.PubMedCrossRefGoogle Scholar
  40. 40.
    Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130:601–30.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Marsland AL, Bachen EA, Cohen S, Rabin B, Manuck SB. Stress, immune reactivity and susceptibility to infectious disease. Physiol Behav. 2002;77:711–6.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol. 2005;5:243–51.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Coussons-Read ME, Okun ML, Schmitt MP, Giese S. Prenatal stress alters cytokine levels in a manner that may endanger human pregnancy: psychosomatic medicine 2005;67:625–631.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    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.PubMedCrossRefGoogle Scholar
  45. 45.
    Culhane JF, Rauh V, McCollum KF, Hogan VK, Agnew K, Wadhwa PD. Maternal stress is associated with bacterial vaginosis in human pregnancy. Matern Child Health J. 2001;5:127–34.PubMedCrossRefGoogle Scholar
  46. 46.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Bronson SL, Bale TL. The placenta as a mediator of stress effects on neurodevelopmental reprogramming. Neuropsychopharmacology. 2016;41:207–18.PubMedCrossRefGoogle Scholar
  48. 48.
    Murphy SK, Fineberg AM, Maxwell SD, Alloy LB, Zimmermann L, Krigbaum NY, et al. Maternal infection and stress during pregnancy and depressive symptoms in adolescent offspring. Psychiatry Res. 2017;257:102–10.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Kourtis AP, Read JS, Jamieson DJ. Pregnancy and infection. N Engl J Med. 2014;370:2211–8.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Deverman BE, Patterson PH. Cytokines and CNS development. Neuron. 2009;64:61–78.PubMedCrossRefGoogle Scholar
  51. 51.
    Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, et al. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry. 2004;161:889–95.PubMedCrossRefGoogle Scholar
  52. 52.
    Goldstein JM, Cherkerzian S, Seidman LJ, Donatelli J-a L, Remington AG, Tsuang MT, et al. Prenatal maternal immune disruption and sex-dependent risk for psychoses. Psychol Med. 2014;44:3249–61.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    • 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. This article proposes that poor coordination between inflammatory markers and glucocorticoids may mediate risk between prenatal maternal stress and offspring neuropsychiatric disorders, including schizophrenia. It also explores how this mechanism may vary across different types of maternal stressors.PubMedCrossRefGoogle Scholar
  54. 54.
    Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Wagner RL, Yolken RH. Maternal cytokine levels during pregnancy and adult psychosis. Brain Behav Immun. 2001;15:411–20.PubMedCrossRefGoogle Scholar
  55. 55.
    Canetta S, Sourander A, Surcel H-M, Hinkka-Yli-Salomäki S, Leiviskä J, Kellendonk C, et al. Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort. Am J Psychiatry. 2014;171:960–8.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Allswede DM, Buka SL, Yolken RH, Torrey EF, Cannon TD. Elevated maternal cytokine levels at birth and risk for psychosis in adult offspring. Schizophr Res. 2016;172:41–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Zijlmans MAC, Korpela K, Riksen-Walraven JM, de Vos WM, de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233–45.PubMedCrossRefGoogle Scholar
  58. 58.
    Sharma S, Norris WE, Kalkunte S. Beyond the threshold: an etiological bridge between hypoxia and immunity in preeclampsia. J Reprod Immunol. 2010;85:112–6.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Zornberg GL, Buka SL, Tsuang MT. Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study. Am J Psychiatry. 2000;157:196–202.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    •• Coussons-Read ME. Effects of prenatal stress on pregnancy and human development: mechanisms and pathways. Obstet Med. 2013;6:52–7. This article describes inflammatory and endocrine pathways to obstetric complications and dysregulated offspring development in response to stress during pregnancy.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Schneider S, Freerksen N, Maul H, Roehrig S, Fischer B, Hoeft B. Risk groups and maternal-neonatal complications of preeclampsia—current results from the national German perinatal quality registry. J Perinat Med. 2011;39:257–65.PubMedCrossRefGoogle Scholar
  62. 62.
    Harville EW, Savitz DA, Dole N, Herring AH, Thorp JM, Light KC. Stress and placental resistance measured by Doppler ultrasound in early and mid-pregnancy. Ultrasound Obstet Gynecol. 2008;32:23–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Helbig A, Kaasen A, Malt UF, Haugen G. Does antenatal maternal psychological distress affect placental circulation in the third trimester? PLoS One. 2013;8:e57071.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Helbig A, Kaasen A, Malt UF, Haugen G. Maternal psychological distress and placental circulation in pregnancies after a previous offspring with congenital malformation. PLoS One. 2014;9:e86597.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Roos A, Geerts L, Koen N, Faure SC, Vythilingum B, Stein DJ. Psychosocial predictors of fetoplacental blood flow during pregnancy. Compr Psychiatry. 2015;57:125–31.PubMedCrossRefGoogle Scholar
  66. 66.
    Knud Larsen J, Bendsen BB, Foldager L, Munk-Jørgensen P. Prematurity and low birth weight as risk factors for the development of affective disorder, especially depression and schizophrenia: a register study. Acta Neuropsychiatr. 2010;22:284–91.PubMedCrossRefGoogle Scholar
  67. 67.
    Fineberg AM, Ellman LM, Buka S, Yolken R, Cannon TD. Decreased birth weight in psychosis: influence of prenatal exposure to serologically determined influenza and hypoxia. Schizophr Bull. 2013;39:1037–44.PubMedCrossRefGoogle Scholar
  68. 68.
    Abel KM, Wicks S, Susser ES, Dalman C, Pedersen MG, Mortensen PB, et al. Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies? Arch Gen Psychiatry. 2010;67:923–30.PubMedCrossRefGoogle Scholar
  69. 69.
    Cherak SJ, Giesbrecht GF, Metcalfe A, Ronksley PE, Malebranche ME. The effect of gestational period on the association between maternal prenatal salivary cortisol and birth weight: a systematic review and meta-analysis. Psychoneuroendocrinology. 2018;94:49–62.PubMedCrossRefGoogle Scholar
  70. 70.
    Wadhwa PD, Sandman CA, Porto M, Dunkel-Schetter C, Garite TJ. The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol. 1993;169:858–65.PubMedCrossRefGoogle Scholar
  71. 71.
    Wadhwa PD. Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology. 2005;30:724–43.PubMedCrossRefGoogle Scholar
  72. 72.
    Ellman LM, Murphy SK, Maxwell SD, Calvo EM, Cooper T, Schaefer CA, Bresnahan MA, Susser ES, Brown AS. Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure. Schizophr Res. 2019.
  73. 73.
    Thayer ZM, Feranil AB, Kuzawa CW. Maternal cortisol disproportionately impacts fetal growth in male offspring: evidence from the Philippines. Am J Hum Biol. 2012;24:1–4.PubMedCrossRefGoogle Scholar
  74. 74.
    Lobel M, Cannella DL, Graham JE, DeVincent C, Schneider J, Meyer BA. Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychol. 2008;27:604–15.PubMedCrossRefGoogle Scholar
  75. 75.
    Auerbach MV, Lobel M, Cannella DT. Psychosocial correlates of health-promoting and health-impairing behaviors in pregnancy. J Psychosom Obstet Gynaecol. 2014;35:76–83.PubMedCrossRefGoogle Scholar
  76. 76.
    Pereira PP d S, Da Mata FAF, Figueiredo ACG, de Andrade KRC, Pereira MG. Maternal active smoking during pregnancy and low birth weight in the Americas: a systematic review and meta-analysis. Nicotine Tob Res. 2017;19:497–505.PubMedCrossRefGoogle Scholar
  77. 77.
    Niemelä S, Sourander A, Surcel H-M, Hinkka-Yli-Salomäki S, McKeague IW, Cheslack-Postava K, et al. Prenatal nicotine exposure and risk of schizophrenia among offspring in a national birth cohort. Am J Psychiatry. 2016;173:799–806.PubMedCrossRefGoogle Scholar
  78. 78.
    Hunter A, Murray R, Asher L, Leonardi-Bee J. The effects of tobacco smoking, and prenatal tobacco smoke exposure, on risk of schizophrenia: a systematic review and meta-analysis. Nicotine Tob Res. 2018.Google Scholar
  79. 79.
    Irwin MR. Why sleep is important for health: a psychoneuroimmunology perspective. Annu Rev Psychol. 2015;66:143–72.PubMedCrossRefGoogle Scholar
  80. 80.
    Bloch JR, Webb DA, Mathews L, Dennis EF, Bennett IM, Culhane JF. Beyond marital status: the quality of the mother-father relationship and its influence on reproductive health behaviors and outcomes among unmarried low income pregnant women. Matern Child Health J. 2010;14:726–34.PubMedCrossRefGoogle Scholar
  81. 81.
    Cornelius T, Desrosiers A, Kershaw T. Smoking concordance during pregnancy: are there relationship benefits? Soc Sci Med. 2017;192:30–5.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Khandaker GM, Dibben CRM, Jones PB. Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring? Obes Rev. 2012;13:518–27.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Schaefer CA, Brown AS, Wyatt RJ, Kline J, Begg MD, Bresnahan MA, et al. Maternal prepregnant body mass and risk of schizophrenia in adult offspring. Schizophr Bull. 2000;26:275–86.PubMedCrossRefGoogle Scholar
  84. 84.
    Simoila L, Isometsä E, Gissler M, Suvisaari J, Halmesmäki E, Lindberg N. Schizophrenia and pregnancy: a national register-based follow-up study among Finnish women born between 1965 and 1980. Arch Womens Ment Health. :2019.Google Scholar
  85. 85.
    Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ. 2017;356:j1.PubMedCrossRefGoogle Scholar
  86. 86.
    Errisuriz VL, Pasch KE, Perry CL. Perceived stress and dietary choices: the moderating role of stress management. Eat Behav. 2016;22:211–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Martins LB, Monteze NM, Calarge C, Ferreira AVM, Teixeira AL. Pathways linking obesity to neuropsychiatric disorders. Nutrition. 2019;66:16–21.PubMedCrossRefGoogle Scholar
  88. 88.
    Ruhstaller KE, Elovitz MA, Stringer M, Epperson CN, Durnwald CP. Obesity and the association with maternal mental health symptoms. J Matern Fetal Neonatal Med. 2017;30:1897–901.PubMedCrossRefGoogle Scholar
  89. 89.
    Segovia SA, Vickers MH, Reynolds CM. The impact of maternal obesity on inflammatory processes and consequences for later offspring health outcomes. J Dev Orig Health Dis. 2017;8:529–40.PubMedCrossRefGoogle Scholar
  90. 90.
    Depino AM. Perinatal inflammation and adult psychopathology: from preclinical models to humans. Semin Cell Dev Biol. 2018;77:104–14.PubMedCrossRefGoogle Scholar
  91. 91.
    Brown AS, Susser ES. Prenatal nutritional deficiency and risk of adult schizophrenia. Schizophr Bull. 2008;34:1054–63.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Lindsay KL, Buss C, Wadhwa PD, Entringer S. The interplay between maternal nutrition and stress during pregnancy: issues and considerations. Ann Nutr Metab. 2017;70:191–200.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    • Liu CH, Keshavan MS, Tronick E, Seidman LJ. Perinatal risks and childhood premorbid indicators of later psychosis: next steps for early psychosocial interventions. Schizophr Bull. 2015;41:801–16. This article implements developmental framework to understand the impact of prenatal stress on premorbid deficits in those in high-risk families for psychosis. It proposes areas of intervention that could be implemented prior to the clinical high-risk phase of psychosis risk.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Burton BK, Hjorthøj C, Jepsen JR, Thorup A, Nordentoft M, Plessen KJ. Research review: do motor deficits during development represent an endophenotype for schizophrenia? A meta-analysis. J Child Psychol Psychiatry. 2016;57:446–56.PubMedCrossRefGoogle Scholar
  95. 95.
    Clarke MC, Tanskanen A, Huttunen M, Leon DA, Murray RM, Jones PB, et al. Increased risk of schizophrenia from additive interaction between infant motor developmental delay and obstetric complications: evidence from a population-based longitudinal study. Am J Psychiatry. 2011;168:1295–302.PubMedCrossRefGoogle Scholar
  96. 96.
    Cao X, Laplante DP, Brunet A, Ciampi A, King S. Prenatal maternal stress affects motor function in 5½-year-old children: project ice storm. Dev Psychobiol. 2014;56:117–25.PubMedCrossRefGoogle Scholar
  97. 97.
    Moss KM, Simcock G, Cobham V, Kildea S, Elgbeili G, Laplante DP, et al. A potential psychological mechanism linking disaster-related prenatal maternal stress with child cognitive and motor development at 16 months: the QF2011 Queensland Flood Study. Dev Psychol. 2017;53:629–41.PubMedCrossRefGoogle Scholar
  98. 98.
    Simcock G, Kildea S, Elgbeili G, Laplante DP, Stapleton H, Cobham V, et al. Age-related changes in the effects of stress in pregnancy on infant motor development by maternal report: the Queensland Flood Study. Dev Psychobiol. 2016;58:640–59.PubMedCrossRefGoogle Scholar
  99. 99.
    Simcock G, Laplante DP, Elgbeili G, Kildea S, King S. A trajectory analysis of childhood motor development following stress in pregnancy: the QF2011 flood study. Dev Psychobiol. 2018;60:836–48.PubMedCrossRefGoogle Scholar
  100. 100.
    Buitelaar JK, Huizink AC, Mulder EJ, de Medina PGR, Visser GHA. Prenatal stress and cognitive development and temperament in infants. Neurobiol Aging. 2003;24(Suppl 1):S53–60 discussion S67–68.PubMedCrossRefGoogle Scholar
  101. 101.
    Grace T, Bulsara M, Robinson M, Hands B. The impact of maternal gestational stress on motor development in late childhood and adolescence: a longitudinal study. Child Dev. 2016;87:211–20.PubMedCrossRefGoogle Scholar
  102. 102.
    Walther S, Mittal VA. Motor system pathology in psychosis. Curr Psychiatry Rep. 2017;19:97.PubMedCrossRefGoogle Scholar
  103. 103.
    Karam F, Sheehy O, Huneau M-C, Chambers C, Fraser WD, Johnson D, et al. Impact of maternal prenatal and parental postnatal stress on 1-year-old child development: results from the OTIS antidepressants in pregnancy study. Arch Womens Ment Health. 2016;19:835–43.PubMedCrossRefGoogle Scholar
  104. 104.
    Laplante DP, Barr RG, Brunet A, Galbaud du Fort G, Meaney ML, Saucier J-F, et al. Stress during pregnancy affects general intellectual and language functioning in human toddlers. Pediatr Res. 2004;56:400–10.PubMedCrossRefGoogle Scholar
  105. 105.
    Laplante DP, Brunet A, Schmitz N, Ciampi A, King S. Project ice storm: prenatal maternal stress affects cognitive and linguistic functioning in 5 1/2-year-old children. J Am Acad Child Adolesc Psychiatry. 2008;47:1063–72.PubMedCrossRefGoogle Scholar
  106. 106.
    Virk J, Obel C, Li J, Olsen J. In-utero exposure to bereavement and offspring IQ: a Danish national cohort study. PLoS One. 2014;9:e88477.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Huizink AC, de Medina PGR, Mulder EJH, Visser GHA, Buitelaar JK. Psychological measures of prenatal stress as predictors of infant temperament. J Am Acad Child Adolesc Psychiatry. 2002;41:1078–85.PubMedCrossRefGoogle Scholar
  108. 108.
    Plamondon A, Akbari E, Atkinson L, Steiner M, Meaney MJ, Fleming AS, et al. Spatial working memory and attention skills are predicted by maternal stress during pregnancy. Early Hum Dev. 2015;91:23–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Buss C, Davis EP, Hobel CJ, Sandman CA. Maternal pregnancy-specific anxiety is associated with child executive function at 6-9 years age. Stress. 2011;14:665–76.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Simcock G, Elgbeili G, Laplante DP, Kildea S, Cobham V, Stapleton H, et al. The effects of prenatal maternal stress on early temperament: the 2011 Queensland Flood Study. J Dev Behav Pediatr. 2017;38:310–21.PubMedCrossRefGoogle Scholar
  111. 111.
    Laplante DP, Brunet A, King S. The effects of maternal stress and illness during pregnancy on infant temperament: Project Ice Storm. Pediatr Res. 2016;79:107–13.PubMedCrossRefGoogle Scholar
  112. 112.
    Tees MT, Harville EW, Xiong X, Buekens P, Pridjian G, Elkind-Hirsch K. Hurricane Katrina-related maternal stress, maternal mental health, and early infant temperament. Matern Child Health J. 2010;14:511–8.PubMedCrossRefGoogle Scholar
  113. 113.
    Enlow MB, Devick KL, Brunst KJ, Lipton LR, Coull BA, Wright RJ. Maternal lifetime trauma exposure, prenatal cortisol, and infant negative affectivity. Infancy. 2017;22:492–513.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Buthmann J, Ham J, Davey K, Finik J, Dana K, Pehme P, et al. Infant temperament: repercussions of Superstorm Sandy-related maternal stress. Child Psychiatry Hum Dev. 2019;50:150–62.PubMedCrossRefGoogle Scholar
  115. 115.
    Buss C, Davis EP, Muftuler LT, Head K, Sandman CA. High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children. Psychoneuroendocrinology. 2010;35:141–53.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Straley ME, Van Oeffelen W, Theze S, Sullivan AM, O’Mahony SM, Cryan JF, et al. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation. Brain Behav Immun. 2017;63:21–34.PubMedCrossRefGoogle Scholar
  117. 117.
    Kim DR, Bale TL, Epperson CN. Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep. 2015;17:5.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    St-Pierre J, Laplante DP, Elgbeili G, Dawson PA, Kildea S, King S, et al. Natural disaster-related prenatal maternal stress is associated with alterations in placental glucocorticoid system: the QF2011 Queensland Flood Study. Psychoneuroendocrinology. 2018;94:38–48.PubMedCrossRefGoogle Scholar
  119. 119.
    Ursini G, Punzi G, Chen Q, Marenco S, Robinson JF, Porcelli A, et al. Convergence of placenta biology and genetic risk for schizophrenia. Nat Med. 2018;24:792–801.PubMedCrossRefGoogle Scholar
  120. 120.
    •• Sandman CA, Glynn LM, Davis EP. Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res. 2013;75:327–35. This article substantiates the viability-vulnerability tradeoff hypothesis with evidence, informing the evident increased risk for male offspring exposed to PNMS for risk for particular psychopathology.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Selten J-P, Cantor-Graae E, Nahon D, Levav I, Aleman A, Kahn RS. No relationship between risk of schizophrenia and prenatal exposure to stress during the Six-Day War or Yom Kippur War in Israel. Schizophr Res. 2003;63:131–5.PubMedCrossRefGoogle Scholar
  122. 122.
    Rosa MJ, Nentin F, Bosquet Enlow M, Hacker MR, Pollas N, Coull B, et al. Sex-specific associations between prenatal negative life events and birth outcomes. Stress. 2019:1–7.Google Scholar
  123. 123.
    Wainstock T, Shoham-Vardi I, Glasser S, Anteby E, Lerner-Geva L. Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes. Stress. 2015;18:49–56.PubMedCrossRefGoogle Scholar
  124. 124.
    Class QA, Lichtenstein P, Långström N, D’Onofrio BM. Timing of prenatal maternal exposure to severe life events and adverse pregnancy outcomes: a population study of 2.6 million pregnancies. Psychosom Med. 2011;73:234–41.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    McGowan PO, Matthews SG. Prenatal stress, glucocorticoids, and developmental programming of the stress response. Endocrinology. 2018;159:69–82.PubMedCrossRefGoogle Scholar
  126. 126.
    Bale TL. Sex differences in prenatal epigenetic programming of stress pathways. Stress. 2011;14:348–56.PubMedCrossRefGoogle Scholar
  127. 127.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA, et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat Rev Neurol. 2014;10:643–60.PubMedCrossRefGoogle Scholar
  129. 129.
    Debost J-CPG, Larsen JT, Munk-Olsen T, Mortensen PB, Meyer U, Petersen L. Joint effects of exposure to prenatal infection and peripubertal psychological trauma in schizophrenia. Schizophr Bull. 2017;43:171–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Giovanoli S, Weber L, Meyer U. Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation. Brain Behav Immun. 2014;40:48–54.PubMedCrossRefGoogle Scholar
  131. 131.
    Schlotz W, Phillips DIW. Fetal origins of mental health: evidence and mechanisms. Brain Behav Immun. 2009;23:905–16.PubMedCrossRefGoogle Scholar
  132. 132.
    Bryan TH. Social relationships and verbal interactions of learning disabled children. J Learn Disabil. 1978;11:107–15.PubMedCrossRefGoogle Scholar
  133. 133.
    McIntosh R, Vaughn S, Schumm JS, Haager D, Lee O. Observations of students with learning disabilities in general education classrooms. Except Child. 1993;60:249–61.CrossRefGoogle Scholar
  134. 134.
    Haager D, Watson C, Willows DM. Parent, teacher, peer, and self-reports of the social competence of students with learning disabilities. J Learn Disabil. 1995;28:205–15.PubMedCrossRefGoogle Scholar
  135. 135.
    Schreier A, Wolke D, Thomas K, Horwood J, Hollis C, Gunnell D, et al. Prospective study of peer victimization in childhood and psychotic symptoms in a nonclinical population at age 12 years. Arch Gen Psychiatry. 2009;66:527–36.PubMedCrossRefGoogle Scholar
  136. 136.
    Lataster T, van Os J, Drukker M, Henquet C, Feron F, Gunther N, et al. Childhood victimisation and developmental expression of non-clinical delusional ideation and hallucinatory experiences: victimisation and non-clinical psychotic experiences. Soc Psychiatry Psychiatr Epidemiol. 2006;41:423–8.PubMedCrossRefGoogle Scholar
  137. 137.
    Danese A, Moffitt TE, Arseneault L, Bleiberg BA, Dinardo PB, Gandelman SB, et al. The origins of cognitive deficits in victimized children: implications for neuroscientists and clinicians. Am J Psychiatry. 2017;174:349–61.PubMedCrossRefGoogle Scholar
  138. 138.
    Lee S, Kim C-J, Kim DH. A meta-analysis of the effect of school-based anti-bullying programs. J Child Health Care. 2015;19:136–53.PubMedCrossRefGoogle Scholar
  139. 139.
    Schechter JC, Brennan PA, Smith AK, Stowe ZN, Newport DJ, Johnson KC. Maternal prenatal psychological distress and preschool cognitive functioning: the protective role of positive parental engagement. J Abnorm Child Psychol. 2017;45:249–60.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Davies HT, Crombie IK, Tavakoli M. When can odds ratios mislead? BMJ. 1998;316:989–91.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Abbott PW, Gumusoglu SB, Bittle J, Beversdorf DQ, Stevens HE. Prenatal stress and genetic risk: how prenatal stress interacts with genetics to alter risk for psychiatric illness. Psychoneuroendocrinology. 2018;90:9–21.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Mittal VA, Willhite R, Daley M, Bearden CE, Niendam T, Ellman LM, et al. Obstetric complications and risk for conversion to psychosis among individuals at high clinical risk. Early Interv Psychiatry. 2009;3:226–30.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Harrison PJ. Recent genetic findings in schizophrenia and their therapeutic relevance. J Psychopharmacol (Oxford). 2015;29:85–96.CrossRefGoogle Scholar
  144. 144.
    • Huizink AC, de Rooij SR. Prenatal stress and models explaining risk for psychopathology revisited: generic vulnerability and divergent pathways. Dev Psychopathol. 2018;30:1041–62. A recent exploration of issues of equifinality and multifinality in research on prenatal stress and offspring outcomes, informative to the discussed cascade model in prenatal stress-schizophrenia associations.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PsychologyTemple UniversityPhiladelphiaUSA

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