Does Prenatal Maternal Distress Contribute to Sex Differences in Child Psychopathology?
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Purpose of Review
Prenatal maternal psychological distress is an established risk factor for the development of psychopathology in offspring. The purpose of this review is to evaluate whether sex differences in fetal responses to maternal distress contribute to sex differences in subsequent psychopathology.
Male and female fetuses respond differently to stress signals. We review recent evidence that demonstrates a sex-specific pattern of association between prenatal maternal distress and pathways associated with risk for psychopathology including offspring hypothalamic pituitary adrenocortical (HPA) axis regulation, brain development, and negative emotionality.
Prenatal maternal distress exerts sex-specific consequences on the fetus. These differences may contribute to the well-established sex differences in psychopathology and in particular to greater female vulnerability to develop internalizing problems.
KeywordsPrenatal Stress Sex differences Depression Development Psychopathology
This work supported by the National Institutes of Health [R01 MH 109662; RO1 HD065823; P50MH 096889].
Compliance with Ethics Guidelines
Conflict of Interest
The authors declare that they have no conflict 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
- 4.Eme R. Sex differences in the prevalence and expression of externalizing behavior. In: Beauchaine TP, Hinshaw SP, editors. The Oxford Handbook of Externalizing Spectrum Disorders. New York: Oxford University Press; 2016. p. 239–62.Google Scholar
- 6.• Sandman CA, Glynn LM, Davis EP. Is there a viability–vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res. 2013;75(4):327–35. https://doi.org/10.1016/j.jpsychores.2013.07.009 This study presents evidence that there is a “viability-vulnerability trade off”. Specifically, under conditions of prenatal exposure to adversity, male fetuses are directly impacted via precipitous declines in their mortality and morbidity. Although females are spared this early hit to their survival, their vulnerability may be revealed later in development. CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Van den Bergh BR, Mulder EJ, Mennes M, Glover V. Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev. 2005;29(2):237–58. https://doi.org/10.1016/j.neubiorev.2004.10.007.CrossRefPubMedGoogle Scholar
- 15.Marcus SM. Depression during pregnancy: rates, risks and consequences—Motherisk update 2008. Can J Clin Pharmacol. 2009;16(1):e15–22.Google Scholar
- 16.Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010;67(10):1012–24. https://doi.org/10.1001/archgenpsychiatry.2010.111.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Buss C, Davis EP, Shahbaba B, Pruessner JC, Head K, Sandman CA. Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc Natl Acad Sci. 2012;109(20):201201295–E1319. https://doi.org/10.1073/pnas.1201295109.CrossRefGoogle Scholar
- 34.• Carpenter T, Grecian S, Reynolds R. 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(2):244–55. https://doi.org/10.1017/S204017441600074X This systematic review reports that exposure to adversity during the prenatal period exerts stronger consequences on the HPA axis for girls as compared to boys. Sex-specific consequences of prenatal adversity on the HPA axis may contribute to sex differences in vulnerability to subsequent disease. CrossRefPubMedGoogle Scholar
- 36.Trivers R. Parental investment and sexual selection. In: Gruyter AD, editor. Sexual selection & the descent of man. New York: Aldine Publishing Company; 1972. p. 136–79.Google Scholar
- 42.• Clifton VL. Review: sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta. 2010;31:S33–S9. https://doi.org/10.1016/j.placenta.2009.11.010 This paper proposes that sexually dimorphic responses of the placenta to prenatal signals of adversity contribute to sex differences in fetal growth as well as to morbidity and mortality. This author suggests that male and female fetuses employ different placental responses to adversity and that these differences contribute to neonatal outcomes and survival. CrossRefPubMedGoogle Scholar
- 45.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. https://doi.org/10.1016/j.psyneuen.2018.04.027.CrossRefPubMedGoogle Scholar
- 46.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 emotional wellbeing study. Int J Mol Sci. 2015;16(11):27482–96. https://doi.org/10.3390/ijms161126034.CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Conradt E, Adkins DE, Crowell SE, Monk C, Kobor MS. An epigenetic pathway approach to investigating associations between prenatal exposure to maternal mood disorder and newborn neurobehavior. Dev Psychopathol. 2018;30(3):881–90. https://doi.org/10.1017/S0954579418000688.CrossRefPubMedPubMedCentralGoogle Scholar
- 49.DiPietro JA, Voegtline KM. The gestational foundation of sex differences in development and vulnerability. J Neurosci. 2017;342:4–20. https://doi.org/10.1016/j.neuroscience.2015.07.068.CrossRefGoogle Scholar
- 55.Van den Bergh BR, 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(3):536–45. https://doi.org/10.1038/sj.npp.1301450.CrossRefPubMedGoogle Scholar
- 56.Stonawski V, Frey S, Golub Y, Rohleder N, Kriebel J, Goecke TW, et al. Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children. Dev Psychopathol. 2018:1–13. https://doi.org/10.1017/S0954579418000056.
- 59.• Wen D, Poh J, Ni S, Chong Y, Chen H, Kwek K, et al. Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children. Transl Psychiatry. 2017;7(4):e1103. https://doi.org/10.1038/tp.2017.74 In this large prospective cohort prenatal maternal depressive symptoms predict enlarged amygdala volume in girls, but not boys after covarying postnatal maternal depressive symptoms. Postnatal depressive symptoms, did not predict amygdala volume, but were associated with microstructure of the right amygdala only in girls. CrossRefPubMedPubMedCentralGoogle Scholar
- 61.• Graham AM, Rasmussen JM, Entringer S, Ben Ward E, Rudolph MD, Gilmore JH, et al. Maternal cortisol concentrations during pregnancy and sex specific associations with neonatal amygdala connectivity and emerging internalizing behaviors. Biol Psychiatry. 2018. https://doi.org/10.1016/j.biopsych.2018.06.023 In this recent longitudinal study, that elevated maternal cortisol predicts neonatal functional connectivity in the amygdala and higher internalizing symptoms in 2 year-old girls, but not boys. Functional connectivity of the amygdala mediated the association between prenatal maternal stress and child internalizing problems in girls.
- 64.• Sandman CA, Curran MM, Davis EP, Glynn LM, Head K, Baram TZ. Cortical thinning and neuropsychiatric outcomes in children exposed to prenatal adversity: a role for placental CRH? Am J Psychiatr. 2018;175(5):471–9. https://doi.org/10.1176/appi.ajp.2017.16121433 Results of this prospective and longitudinal study revealed that elevated prenatal placental CRH concentrations predicted cortical thinning in childhood. The impact of placental CRH on cortical thinness is stronger among girls as compared to boys. These sex specific consequences of placental CRH on the developing brain may contribute to greater female vulnerability to internalizing psychopathology. CrossRefPubMedGoogle Scholar
- 65.Madigan S, Oatley H, Racine N, Fearon RMP, Schumacher L, Akbari E, et al. A meta-analysis of maternal prenatal depression and anxiety on child socioemotional development. J Am Acad Child Adolesc Psychiatry. 2018;57(9):645–57 e8. https://doi.org/10.1016/j.jaac.2018.06.012.CrossRefPubMedGoogle Scholar
- 74.Hill J, Pickles A, Wright N, Quinn JP, Murgatroyd C, Sharp H. Maternal depression and child behaviours: sex-dependent mediation by glucocorticoid receptor gene methylation in a longitudinal study from pregnancy to age 5 years. bioRxiv. 2017:187351. https://doi.org/10.1101/187351.
- 76.• Quarini C, Pearson RM, Stein A, Ramchandani PG, Lewis G, Evans J. Are female children more vulnerable to the long-term effects of maternal depression during pregnancy? J Affect Disord. 2016;189:329–35. https://doi.org/10.1016/j.jad.2015.09.039 This longitudinal study finds that girls of prenatally depressed mothers were at higher risk for depression diagnosis at 18 years of age, compared to boys. This finding remained even after covarying effects of postnatal maternal depression as well as other confounds. CrossRefPubMedPubMedCentralGoogle Scholar
- 79.Barker ED, Oliver BR, Viding E, Salekin RT, Maughan B. The impact of prenatal maternal risk, fearless temperament and early parenting on adolescent callous-unemotional traits: a 14-year longitudinal investigation. J Child Psychol Psychiatry. 2011;52(8):878–88. https://doi.org/10.1111/j.1469-7610.2011.02397.x.CrossRefPubMedGoogle Scholar
- 81.Pearson RM, Evans J, Kounali D, Lewis G, Heron J, Ramchandani PG, et al. Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years. JAMA Psychiatry. 2013;70(12):1312–9. https://doi.org/10.1001/jamapsychiatry.2013.2163.CrossRefPubMedPubMedCentralGoogle Scholar
- 87.Davis EP, Hankin BL, Swales DA, Hoffman MC. An experimental test of the fetal programming hypothesis: can we reduce child ontogenetic vulnerability to psychopathology by decreasing maternal depression? Dev Psychopathol. 2018;30(3):787–806. https://doi.org/10.1017/S0954579418000470.CrossRefPubMedGoogle Scholar
- 88.Glasheen C, Richardson GA, Kim KH, Larkby CA, Swartz HA, Day NL. Exposure to maternal pre-and postnatal depression and anxiety symptoms: risk for major depression, anxiety disorders, and conduct disorder in adolescent offspring. Dev Psychopathol. 2013;25(4pt1):1045–63. https://doi.org/10.1017/S0954579413000369.CrossRefPubMedPubMedCentralGoogle Scholar
- 89.Eichler A, Walz L, Grunitz J, Grimm J, Van Doren J, Raabe E, et al. Children of prenatally depressed mothers: externalizing and internalizing symptoms are accompanied by reductions in specific social-emotional competencies. J Child Fam Stud. 2017;26(11):3135–44. https://doi.org/10.1007/s10826-017-0819-0.CrossRefGoogle Scholar
- 90.Howland MA, Sandman CA, Glynn LM, Crippen C, Davis EP. Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms. Psychoneuroendocrinology. 2016;67:10–7. https://doi.org/10.1016/j.psyneuen.2016.01.023.CrossRefPubMedPubMedCentralGoogle Scholar
- 93.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(2):249–60. https://doi.org/10.1007/s10802-016-0161-9.CrossRefPubMedPubMedCentralGoogle Scholar