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Intergenerational Aspects of Immune and Endocrine Function in Perinatal Depression

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Perinatal Inflammation and Adult Psychopathology

Part of the book series: Progress in Inflammation Research ((PIR,volume 84))

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Abstract

Perinatal depression mediates a profound impact on maternal and offspring health. Alterations in endocrine and immune function in depressed mothers have been linked to altered stress responses in offspring and less optimal neurodevelopmental outcomes. This chapter reviews the important changes in immune function that have been documented in depressed mothers and seeks to link changes in immune regulatory and endocrine processes to ultimate outcome in offspring. We identify key interactions between the immune system, the Hypothalamic-Pituitary-Adrenal axis and the oxytocin system that are relevant to understanding the dysregulated immune responses in depressed mothers. Additionally, we review how the above changes have been linked to an increased risk of aberrant development of offspring of depressed mothers, as well as the future manifestation of mental illness. Molecular mechanisms relevant to these processes are highlighted. Our work reinforces the potential importance of biomarkers that could be linked to both immune dysfunction and negative developmental outcomes in offspring in perinatal depression. Through improved screening and intervention protocols that incorporate the above approach, significant progress could be made in reducing the large morbidity associated with perinatal depression.

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References

  1. Stein A, Pearson RM, Goodman SH, et al. Effects of perinatal mental disorders on the fetus and child. Lancet. 2014;384(9956):1800–19. https://doi.org/10.1016/S0140-6736(14)61277-0.

    Article  PubMed  Google Scholar 

  2. Gavin NI, Gaynes BN, Lohr KN, et al. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol. 2005;106(5 Pt 1):1071–83. https://doi.org/10.1097/01.AOG.0000183597.31630.db.

    Article  PubMed  Google Scholar 

  3. Giardinelli L, Innocenti A, Benni L, et al. Depression and anxiety in perinatal period: prevalence and risk factors in an Italian sample. Arch Womens Ment Health. 2012;15(1):21–30. https://doi.org/10.1007/s00737-011-0249-8.

    Article  CAS  PubMed  Google Scholar 

  4. Biaggi A, Conroy S, Pawlby S, et al. Identifying the women at risk of antenatal anxiety and depression: a systematic review. J Affect Disord. 2016;191:62–77. https://doi.org/10.1016/j.jad.2015.11.014.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cooper PJ, Campbell EA, Day A, et al. Non-psychotic psychiatric disorder after childbirth. A prospective study of prevalence, incidence, course and nature. Br J Psychiatry. 1988;152:799–806.

    Article  CAS  PubMed  Google Scholar 

  6. Areias ME, Kumar R, Barros H, et al. Comparative incidence of depression in women and men, during pregnancy and after childbirth. Validation of the Edinburgh postnatal depression scale in Portuguese mothers. Br J Psychiatry. 1996;169(1):30–5.

    Article  CAS  PubMed  Google Scholar 

  7. Banti S, Mauri M, Oppo A, et al. From the third month of pregnancy to 1 year postpartum. Prevalence, incidence, recurrence, and new onset of depression. Results from the perinatal depression-research & screening unit study. Compr Psychiatry. 2011;52(4):343–51. https://doi.org/10.1016/j.comppsych.2010.08.003.

    Article  PubMed  Google Scholar 

  8. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013;74(4):321. https://doi.org/10.4088/JCP.12r07968.

    Article  Google Scholar 

  9. Grote NK, Bridge JA, Gavin AR, et al. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Leis JA, Heron J, Stuart EA, et al. Associations between maternal mental health and child emotional and behavioral problems: does prenatal mental health matter? J Abnorm Child Psychol. 2014;42(1):161–71. https://doi.org/10.1007/s10802-013-9766-4.

    Article  PubMed  Google Scholar 

  11. Velders FP, Dieleman G, Henrichs J, et al. Prenatal and postnatal psychological symptoms of parents and family functioning: the impact on child emotional and behavioural problems. Eur Child Adolesc Psychiatry. 2011;20(7):341–50. https://doi.org/10.1007/s00787-011-0178-0.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Van Batenburg-Eddes T, Brion MJ, Henrichs J, et al. Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study. J Child Psychol Psychiatry. 2013;54(5):591–600. https://doi.org/10.1111/jcpp.12023.

    Article  PubMed  Google Scholar 

  13. Verbeek T, Bockting CLH, van Pampus MG, et al. Postpartum depression predicts offspring mental health problems in adolescence independently of parental lifetime psychopathology. J Affect Disord. 2012;136(3):948–54. https://doi.org/10.1016/j.jad.2011.08.035.

    Article  PubMed  Google Scholar 

  14. Barker ED, Jaffee SR, Uher R, et al. The contribution of prenatal and postnatal maternal anxiety and depression to child maladjustment. Depress Anxiety. 2011;28(8):696–702. https://doi.org/10.1002/da.20856.

    Article  PubMed  Google Scholar 

  15. Galéra C, Côté SM, Bouvard MP, et al. Early risk factors for hyperactivity-impulsivity and inattention trajectories from age 17 months to 8 years. Arch Gen Psychiatry. 2011;68(12):1267–75. https://doi.org/10.1001/archgenpsychiatry.2011.138.

    Article  PubMed  Google Scholar 

  16. Hanington L, Heron J, Stein A, et al. Parental depression and child outcomes – is marital conflict the missing link? Child Care Health Dev. 2012;38(4):520–9. https://doi.org/10.1111/j.1365-2214.2011.01270.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Letourneau NL, Tramonte L, Willms JD. Maternal depression, family functioning and children’s longitudinal development. J Pediatr Nurs. 2013;28(3):223–34. https://doi.org/10.1016/j.pedn.2012.07.014.

    Article  PubMed  Google Scholar 

  18. Evans J, Melotti R, Heron J, et al. The timing of maternal depressive symptoms and child cognitive development: a longitudinal study. J Child Psychol Psychiatry. 2012;53(6):632–40. https://doi.org/10.1111/j.1469-7610.2011.02513.x.

    Article  PubMed  Google Scholar 

  19. Feldman R, Granat A, Pariente C, et al. Maternal depression and anxiety across the postpartum year and infant social engagement, fear regulation, and stress reactivity. J Am Acad Child Adolesc Psychiatry. 2009;48(9):919–27. https://doi.org/10.1097/CHI.0b013e3181b21651.

    Article  PubMed  Google Scholar 

  20. Granat A, Gadassi R, Gilboa-Schechtman E, et al. Maternal depression and anxiety, social synchrony, and infant regulation of negative and positive emotions. Emotion. 2017;17(1):11–27. https://doi.org/10.1037/emo0000204.

    Article  PubMed  Google Scholar 

  21. Murray L. The impact of postnatal depression on infant development. J Child Psychol Psychiatry. 1992;33(3):543–61.

    Article  CAS  PubMed  Google Scholar 

  22. Pearson RM, Evans J, Kounali D, et al. Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years. JAMA Psychiat. 2013;70(12):1312–9. https://doi.org/10.1001/jamapsychiatry.2013.2163.

    Article  Google Scholar 

  23. Pawlby S, Hay DF, Sharp D, et al. Antenatal depression predicts depression in adolescent offspring: prospective longitudinal community-based study. J Affect Disord. 2009;113(3):236–43. https://doi.org/10.1016/j.jad.2008.05.018.

    Article  PubMed  Google Scholar 

  24. O’Donnell KJ, Glover V, Barker ED, et al. The persisting effect of maternal mood in pregnancy on childhood psychopathology. Dev Psychopathol. 2014;26(2):393–403. https://doi.org/10.1017/S0954579414000029.

    Article  PubMed  Google Scholar 

  25. Hay DF, Pawlby S, Waters CS, et al. Antepartum and postpartum exposure to maternal depression: different effects on different adolescent outcomes. J Child Psychol Psychiatry. 2008;49(10):1079–88. https://doi.org/10.1111/j.1469-7610.2008.01959.x.

    Article  PubMed  Google Scholar 

  26. Previti G, Pawlby S, Chowdhury S, et al. Neurodevelopmental outcome for offspring of women treated for antenatal depression: a systematic review. Arch Womens Ment Health. 2014;17(6):471–83. https://doi.org/10.1007/s00737-014-0457-0.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Qiu A, Anh TT, Li Y, et al. Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants. Transl Psychiatry. 2015;5:e508. https://doi.org/10.1038/tp.2015.3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Soe NN, Wen DJ, Poh JS, et al. Perinatal maternal depressive symptoms alter amygdala functional connectivity in girls. Hum Brain Mapp. 2018;39(2):680–90. https://doi.org/10.1002/hbm.23873.

    Article  PubMed  Google Scholar 

  29. Naicker K, Wickham M, Colman I. Timing of first exposure to maternal depression and adolescent emotional disorder in a national Canadian cohort. PLoS One. 2012;7(3):e33422. https://doi.org/10.1371/journal.pone.0033422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Reynolds RM. Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis – 2012 Curt Richter award winner. Psychoneuroendocrinology. 2013;38(1):1–11. https://doi.org/10.1016/j.psyneuen.2012.08.012.

    Article  CAS  PubMed  Google Scholar 

  31. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: outcomes. Nat Rev Endocrinol. 2014;10(7):391–402. https://doi.org/10.1038/nrendo.2014.73.

    Article  CAS  PubMed  Google Scholar 

  32. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 2: mechanisms. Nat Rev Endocrinol. 2014;10(7):403–11. https://doi.org/10.1038/nrendo.2014.74.

    Article  CAS  PubMed  Google Scholar 

  33. Glover V. Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms. Adv Neurobiol. 2015;10:269–83. https://doi.org/10.1007/978-1-4939-1372-5_13.

    Article  PubMed  Google Scholar 

  34. Gutteling BM, de Weerth C, Buitelaar JK. Maternal prenatal stress and 4-6 year old children’s salivary cortisol concentrations pre- and post-vaccination. Stress. 2004;7(4):257–60. https://doi.org/10.1080/10253890500044521.

    Article  CAS  PubMed  Google Scholar 

  35. Gutteling BM, de Weerth C, Buitelaar JK. Prenatal stress and children’s cortisol reaction to the first day of school. Psychoneuroendocrinology. 2005;30(6):541–9. https://doi.org/10.1016/j.psyneuen.2005.01.002.

    Article  CAS  PubMed  Google Scholar 

  36. O’Connor TG, Bergman K, Sarkar P, et al. Prenatal cortisol exposure predicts infant cortisol response to acute stress. Dev Psychobiol. 2013;55(2):145–55. https://doi.org/10.1002/dev.21007.

    Article  CAS  PubMed  Google Scholar 

  37. de Weerth C, van Hees Y, Buitelaar JK. Prenatal maternal cortisol levels and infant behavior during the first 5 months. Early Hum Dev. 2003;74(2):139–51.

    Article  PubMed  Google Scholar 

  38. Davis EP, Glynn LM, Schetter CD, et al. Prenatal exposure to maternal depression and cortisol influences infant temperament. J Am Acad Child Adolesc Psychiatry. 2007;46(6):737–46. https://doi.org/10.1097/chi.0b013e318047b775.

    Article  PubMed  Google Scholar 

  39. 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(1):131–48. https://doi.org/10.1111/j.1467-8624.2009.01385.x.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Rich-Edwards JW, Mohllajee AP, Kleinman K, et al. Elevated midpregnancy corticotropin-releasing hormone is associated with prenatal, but not postpartum, maternal depression. J Clin Endocrinol Metab. 2008;93(5):1946–51. https://doi.org/10.1210/jc.2007-2535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. O’Connor TG, Tang W, Gilchrist MA, et al. Diurnal cortisol patterns and psychiatric symptoms in pregnancy: short-term longitudinal study. Biol Psychol. 2014;96:35–41. https://doi.org/10.1016/j.biopsycho.2013.11.002.

    Article  PubMed  Google Scholar 

  42. O’Keane V, Lightman S, Marsh M, et al. Increased pituitary-adrenal activation and shortened gestation in a sample of depressed pregnant women: a pilot study. J Affect Disord. 2011;130(1–2):300–5. https://doi.org/10.1016/j.jad.2010.10.004.

    Article  CAS  PubMed  Google Scholar 

  43. Li XQ, Zhu P, Myatt L, et al. Roles of glucocorticoids in human parturition: a controversial fact? Placenta. 2014;35(5):291–6. https://doi.org/10.1016/j.placenta.2014.03.005.

    Article  CAS  PubMed  Google Scholar 

  44. Sasaki A, Liotta AS, Luckey MM, et al. Immunoreactive corticotropin-releasing factor is present in human maternal plasma during the third trimester of pregnancy. J Clin Endocrinol Metab. 1984;59(4):812–4. https://doi.org/10.1210/jcem-59-4-812.

    Article  CAS  PubMed  Google Scholar 

  45. Magiakou MA, Mastorakos G, Rabin D, et al. The maternal hypothalamic-pituitary-adrenal axis in the third trimester of human pregnancy. Clin Endocrinol. 1996;44(4):419–28.

    Article  CAS  Google Scholar 

  46. Osborne S, Biaggi A, Chua TE, et al. Antenatal depression programs cortisol stress reactivity in offspring through increased maternal inflammation and cortisol in pregnancy: The Psychiatry Research and Motherhood – Depression (PRAM-D) study. Psychoneuroendocrinology. 2018;98:211–21. https://doi.org/10.1016/j.psyneuen.2018.06.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Magiakou MA, Mastorakos G, Rabin D, et al. Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time. J Clin Endocrinol Metab. 1996;81(5):1912–7. https://doi.org/10.1210/jcem.81.5.8626857.

    Article  CAS  PubMed  Google Scholar 

  48. Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Ann N Y Acad Sci. 2012;1261:55–63. https://doi.org/10.1111/j.1749-6632.2012.06633.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 2003;160(9):1554–65. https://doi.org/10.1176/appi.ajp.160.9.1554.

    Article  PubMed  Google Scholar 

  50. Nadeau S, Rivest S. Glucocorticoids play a fundamental role in protecting the brain during innate immune response. J Neurosci. 2003;23(13):5536–44.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Johnson RW, Propes MJ, Shavit Y. Corticosterone modulates behavioral and metabolic effects of lipopolysaccharide. Am J Phys. 1996;270(1 Pt 2):192. https://doi.org/10.1152/ajpregu.1996.270.1.R192.

    Article  Google Scholar 

  52. Pezeshki G, Pohl T, Schöbitz B. Corticosterone controls interleukin-1 beta expression and sickness behavior in the rat. J Neuroendocrinol. 1996;8(2):129–35.

    Article  CAS  PubMed  Google Scholar 

  53. Wang D, Lin W, Pan Y, et al. Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats. Brain Behav Immun. 2011;25(4):706–14. https://doi.org/10.1016/j.bbi.2011.01.011.

    Article  CAS  PubMed  Google Scholar 

  54. Pace TWW, Hu F, Miller AH. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun. 2007;21(1):9–19. https://doi.org/10.1016/j.bbi.2006.08.009.

    Article  CAS  PubMed  Google Scholar 

  55. Leff-Gelman P, Mancilla-Herrera I, Flores-Ramos M, et al. The immune system and the role of inflammation in perinatal depression. Neurosci Bull. 2016;32(4):398–420. https://doi.org/10.1007/s12264-016-0048-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Walsh K, Basu A, Werner E, et al. Associations among child abuse, depression, and Interleukin-6 in pregnant adolescents: paradoxical findings. Psychosom Med. 2016;78(8):920–30. https://doi.org/10.1097/PSY.0000000000000344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Plant DT, Pariante CM, Sharp D, et al. Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment. Br J Psychiatry. 2015;207(3):213–20. https://doi.org/10.1192/bjp.bp.114.156620.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Bränn E, Fransson E, White RA, et al. Inflammatory markers in women with postpartum depressive symptoms. J Neurosci Res. 2018; https://doi.org/10.1002/jnr.24312.

  59. Osborne LM, Yenokyan G, Fei K, et al. Innate immune activation and depressive and anxious symptoms across the peripartum: an exploratory study. Psychoneuroendocrinology. 2019;99:80–6. https://doi.org/10.1016/j.psyneuen.2018.08.038.

    Article  PubMed  Google Scholar 

  60. Shelton MM, Schminkey DL, Groer MW. Relationships among prenatal depression, plasma cortisol, and inflammatory cytokines. Biol Res Nurs. 2015;17(3):295–302. https://doi.org/10.1177/1099800414543821.

    Article  CAS  PubMed  Google Scholar 

  61. Edvinsson Å, Bränn E, Hellgren C, et al. Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction. Psychoneuroendocrinology. 2017;80:15–25. https://doi.org/10.1016/j.psyneuen.2017.02.027.

    Article  CAS  PubMed  Google Scholar 

  62. Graham AM, Rasmussen JM, Rudolph MD, et al. Maternal systemic Interleukin-6 during pregnancy is associated with newborn amygdala phenotypes and subsequent behavior at 2 years of age. Biol Psychiatry. 2018;83(2):109–19. https://doi.org/10.1016/j.biopsych.2017.05.027.

    Article  CAS  PubMed  Google Scholar 

  63. Plant DT, Pawlby S, Sharp D, et al. Prenatal maternal depression is associated with offspring inflammation at 25 years: a prospective longitudinal cohort study. Transl Psychiatry. 2016;6(11):e936. https://doi.org/10.1038/tp.2015.155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wirleitner B, Neurauter G, Schröcksnadel K, et al. Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects. Curr Med Chem. 2003;10(16):1581–91.

    Article  CAS  PubMed  Google Scholar 

  65. Champagne FA. Epigenetic mechanisms and the transgenerational effects of maternal care. Front Neuroendocrinol. 2008;29(3):386–97. https://doi.org/10.1016/j.yfrne.2008.03.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bowers ME, Yehuda R. Intergenerational transmission of stress in humans. Neuropsychopharmacology. 2016;41(1):232–44. https://doi.org/10.1038/npp.2015.247.

    Article  PubMed  Google Scholar 

  67. Sureshchandra S, Wilson RM, Rais M, et al. Maternal Pregravid obesity remodels the DNA methylation landscape of cord blood monocytes disrupting their inflammatory program. J Immunol. 2017;199(8):2729–44. https://doi.org/10.4049/jimmunol.1700434.

    Article  CAS  PubMed  Google Scholar 

  68. Sureshchandra S, Marshall NE, Wilson RM, et al. Inflammatory determinants of Pregravid obesity in placenta and peripheral blood. Front Physiol. 2018;9:1089. https://doi.org/10.3389/fphys.2018.01089.

    Article  PubMed  PubMed Central  Google Scholar 

  69. van Otterdijk SD, Binder AM, Michels KB. Locus-specific DNA methylation in the placenta is associated with levels of pro-inflammatory proteins in cord blood and they are both independently affected by maternal smoking during pregnancy. Epigenetics. 2017;12(10):875–85. https://doi.org/10.1080/15592294.2017.1361592.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Schlinzig T, Johansson S, Gunnar A, et al. Epigenetic modulation at birth – altered DNA-methylation in white blood cells after caesarean section. Acta Paediatr. 2009;98(7):1096–9. https://doi.org/10.1111/j.1651-2227.2009.01371.x.

    Article  CAS  PubMed  Google Scholar 

  71. Essex MJ, Boyce WT, Hertzman C, et al. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Dev. 2013;84(1):58–75. https://doi.org/10.1111/j.1467-8624.2011.01641.x.

    Article  PubMed  Google Scholar 

  72. Weaver ICG, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847–54. https://doi.org/10.1038/nn1276.

    Article  CAS  PubMed  Google Scholar 

  73. Champagne FA, Weaver ICG, Diorio J, et al. Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology. 2006;147(6):2909–15. https://doi.org/10.1210/en.2005-1119.

    Article  CAS  PubMed  Google Scholar 

  74. Franklin TB, Russig H, Weiss IC, et al. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry. 2010;68(5):408–15. https://doi.org/10.1016/j.biopsych.2010.05.036.

    Article  PubMed  Google Scholar 

  75. Nemoda Z, Massart R, Suderman M, et al. Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi. Transl Psychiatry. 2015;5:e545. https://doi.org/10.1038/tp.2015.32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sawyer KM, Zunszain PA, Dazzan P, et al. Intergenerational transmission of depression: clinical observations and molecular mechanisms. Mol Psychiatry. 2019;24(8):1157–77. https://doi.org/10.1038/s41380-018-0265-4.

    Article  PubMed  Google Scholar 

  77. Cattaneo A, Cattane N, Malpighi C, et al. FoxO1, A2M, and TGF-β1: three novel genes predicting depression in gene X environment interactions are identified using cross-species and cross-tissues transcriptomic and miRNomic analyses. Mol Psychiatry. 2018;23(11):2192–208. https://doi.org/10.1038/s41380-017-0002-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kendler KS, Gatz M, Gardner CO, et al. A Swedish national twin study of lifetime major depression. Am J Psychiatry. 2006;163(1):109–14. https://doi.org/10.1176/appi.ajp.163.1.109.

    Article  PubMed  Google Scholar 

  79. Couto TCE, Brancaglion MYM, Alvim-Soares A, et al. Postpartum depression: a systematic review of the genetics involved. World J Psychiatry. 2015;5(1):103–11. https://doi.org/10.5498/wjp.v5.i1.103.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Mahon PB, Payne JL, MacKinnon DF, et al. Genome-wide linkage and follow-up association study of postpartum mood symptoms. Am J Psychiatry. 2009;166(11):1229–37. https://doi.org/10.1176/appi.ajp.2009.09030417.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Viktorin A, Meltzer-Brody S, Kuja-Halkola R, et al. Heritability of perinatal depression and genetic overlap with nonperinatal depression. Am J Psychiatry. 2016;173(2):158–65. https://doi.org/10.1176/appi.ajp.2015.15010085.

    Article  PubMed  Google Scholar 

  82. Nomura Y, Wickramaratne PJ, Pilowsky DJ, et al. Low birth weight and risk of affective disorders and selected medical illness in offspring at high and low risk for depression. Compr Psychiatry. 2007;48(5):470–8. https://doi.org/10.1016/j.comppsych.2007.04.005.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Pluess M, Velders FP, Belsky J, et al. Serotonin transporter polymorphism moderates effects of prenatal maternal anxiety on infant negative emotionality. Biol Psychiatry. 2011;69(6):520–5. https://doi.org/10.1016/j.biopsych.2010.10.006.

    Article  CAS  PubMed  Google Scholar 

  84. Wazana A, Moss E, Jolicoeur-Martineau A, et al. The interplay of birth weight, dopamine receptor D4 gene (DRD4), and early maternal care in the prediction of disorganized attachment at 36 months of age. Dev Psychopathol. 2015;27(4 Pt 1):1145–61. https://doi.org/10.1017/S0954579415000735.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Rice F, Harold GT, Boivin J, et al. The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences. Psychol Med. 2010;40(2):335–45. https://doi.org/10.1017/S0033291709005911.

    Article  CAS  PubMed  Google Scholar 

  86. Seth S, Lewis AJ, Saffery R, et al. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. O’Donnell KJ, Bugge Jensen A, Freeman L, et al. Maternal prenatal anxiety and downregulation of placental 11β-HSD2. Psychoneuroendocrinology. 2012;37(6):818–26. https://doi.org/10.1016/j.psyneuen.2011.09.014.

    Article  CAS  PubMed  Google Scholar 

  88. Conradt E, Lester BM, Appleton AA, et al. The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics. 2013;8(12):1321–9. https://doi.org/10.4161/epi.26634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Mikelson C, Kovach MJ, Troisi J, et al. Placental 11β-Hydroxysteroid dehydrogenase type 2 expression: correlations with birth weight and placental metal concentrations. Placenta. 2015;36(11):1212–7. https://doi.org/10.1016/j.placenta.2015.09.011.

    Article  CAS  PubMed  Google Scholar 

  90. Holmes MC, Abrahamsen CT, French KL, et al. The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice provide evidence for direct fetal programming of behavior by endogenous glucocorticoids. J Neurosci. 2006;26(14):3840–4. https://doi.org/10.1523/JNEUROSCI.4464-05.2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Welberg LA, Seckl JR, Holmes MC. Inhibition of 11beta-hydroxysteroid dehydrogenase, the foeto-placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety-like behaviour in the offspring. Eur J Neurosci. 2000;12(3):1047–54.

    Article  CAS  PubMed  Google Scholar 

  92. Conradt E, Fei M, LaGasse L, et al. Prenatal predictors of infant self-regulation: the contributions of placental DNA methylation of NR3C1 and neuroendocrine activity. Front Behav Neurosci. 2015;9:130. https://doi.org/10.3389/fnbeh.2015.00130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Jones RL, Hannan NJ, Kaitu’u TJ, et al. Identification of chemokines important for leukocyte recruitment to the human endometrium at the times of embryo implantation and menstruation. J Clin Endocrinol Metab. 2004;89(12):6155–67. https://doi.org/10.1210/jc.2004-0507.

    Article  CAS  PubMed  Google Scholar 

  94. Speirs HJL, Seckl JR, Brown RW. Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development. J Endocrinol. 2004;181(1):105–16.

    Article  CAS  PubMed  Google Scholar 

  95. McLean M, Bisits A, Davies J, et al. A placental clock controlling the length of human pregnancy. Nat Med. 1995;1(5):460–3.

    Article  CAS  PubMed  Google Scholar 

  96. 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(7):2635–46. https://doi.org/10.1210/en.2014-1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Goland RS, Tropper PJ, Warren WB, et al. Concentrations of corticotrophin-releasing hormone in the umbilical-cord blood of pregnancies complicated by pre-eclampsia. Reprod Fertil Dev. 1995;7(5):1227–30.

    Article  CAS  PubMed  Google Scholar 

  98. Gur TL, Shay L, Palkar AV, 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  PubMed  Google Scholar 

  99. Henriques TP, Szawka RE, Diehl LA, et al. Stress in neonatal rats with different maternal care backgrounds: monoaminergic and hormonal responses. Neurochem Res. 2014;39(12):2351–9. https://doi.org/10.1007/s11064-014-1434-8.

    Article  CAS  PubMed  Google Scholar 

  100. Champagne FA, Meaney MJ. Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol Psychiatry. 2006;59(12):1227–35. https://doi.org/10.1016/j.biopsych.2005.10.016.

    Article  CAS  PubMed  Google Scholar 

  101. Champagne F, Diorio J, Sharma S, et al. Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci U S A. 2001;98(22):12736–41. https://doi.org/10.1073/pnas.221224598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Feldman R, Weller A, Zagoory-Sharon O, et al. Evidence for a neuroendocrinological foundation of human affiliation: plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding. Psychol Sci. 2007;18(11):965–70. https://doi.org/10.1111/j.1467-9280.2007.02010.x.

    Article  PubMed  Google Scholar 

  103. Eapen V, Dadds M, Barnett B, et al. Separation anxiety, attachment and inter-personal representations: disentangling the role of oxytocin in the perinatal period. PLoS One. 2014;9(9):e107745. https://doi.org/10.1371/journal.pone.0107745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Skrundz M, Bolten M, Nast I, et al. Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology. 2011;36(9):1886–93. https://doi.org/10.1038/npp.2011.74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Mileva-Seitz V, Steiner M, Atkinson L, et al. Interaction between oxytocin genotypes and early experience predicts quality of mothering and postpartum mood. PLoS One. 2013;8(4):e61443. https://doi.org/10.1371/journal.pone.0061443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Pratt M, Apter-Levi Y, Vakart A, et al. Maternal depression and child oxytocin response; moderation by maternal oxytocin and relational behavior. Depress Anxiety. 2015;32(9):635–46. https://doi.org/10.1002/da.22392.

    Article  CAS  PubMed  Google Scholar 

  107. Feldman R, Gordon I, Influs M, et al. Parental oxytocin and early caregiving jointly shape children’s oxytocin response and social reciprocity. Neuropsychopharmacology. 2013;38(7):1154–62. https://doi.org/10.1038/npp.2013.22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Strathearn L, Fonagy P, Amico J, et al. Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychopharmacology. 2009;34(13):2655–66. https://doi.org/10.1038/npp.2009.103.

    Article  CAS  PubMed  Google Scholar 

  109. Toepfer P, Heim C, Entringer S, et al. Oxytocin pathways in the intergenerational transmission of maternal early life stress. Neurosci Biobehav Rev. 2017;73:293–308. https://doi.org/10.1016/j.neubiorev.2016.12.026.

    Article  CAS  PubMed  Google Scholar 

  110. Cox EQ, Stuebe A, Pearson B, et al. Oxytocin and HPA stress axis reactivity in postpartum women. Psychoneuroendocrinology. 2015;55:164–72. https://doi.org/10.1016/j.psyneuen.2015.02.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Heinrichs M, Meinlschmidt G, Neumann I, et al. Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women. J Clin Endocrinol Metab. 2001;86(10):4798–804. https://doi.org/10.1210/jcem.86.10.7919.

    Article  CAS  PubMed  Google Scholar 

  112. Li T, Wang P, Wang SC, et al. Approaches mediating oxytocin regulation of the immune system. Front Immunol. 2016;7:693. https://doi.org/10.3389/fimmu.2016.00693.

    Article  PubMed  Google Scholar 

  113. Wang P, Yang H, Tian S, et al. Oxytocin-secreting system: a major part of the neuroendocrine center regulating immunologic activity. J Neuroimmunol. 2015;289:152–61. https://doi.org/10.1016/j.jneuroim.2015.11.001.

    Article  CAS  PubMed  Google Scholar 

  114. Clodi M, Vila G, Geyeregger R, et al. Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men. Am J Physiol Endocrinol Metab. 2008;295(3):686. https://doi.org/10.1152/ajpendo.90263.2008.

    Article  Google Scholar 

  115. Yuan L, Liu S, Bai X, et al. Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice. J Neuroinflammation. 2016;13(1):77. https://doi.org/10.1186/s12974-016-0541-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Schmid B, Wong S, Mitchell BF. Transcriptional regulation of oxytocin receptor by interleukin-1beta and interleukin-6. Endocrinology. 2001;142(4):1380–5. https://doi.org/10.1210/endo.142.4.8107.

    Article  CAS  PubMed  Google Scholar 

  117. Pearson RM, Carnegie RE, Cree C, et al. Prevalence of prenatal depression symptoms among 2 generations of pregnant mothers: the Avon longitudinal study of parents and children. JAMA Netw Open. 2018;1(3):e180725. https://doi.org/10.1001/jamanetworkopen.2018.0725.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Plant DT, Jones FW, Pariante CM, et al. Association between maternal childhood trauma and offspring childhood psychopathology: mediation analysis from the ALSPAC cohort. Br J Psychiatry. 2017;211(3):144–50. https://doi.org/10.1192/bjp.bp.117.198721.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

AJP is the recipient of career development funding from the Province of British Columbia through the Clinician Investigator Program at the University of British Columbia (UBC), the Detweiler Travelling Fellowship from the Royal College of Physicians and Surgeons of Canada and the Friedman Award for Scholars in Health from UBC. CMP is supported by grants from Immunopsychiatry: A Consortium to Test the Opportunity for Immunotherapeutics in Psychiatry (MR/L014815/1) and the Medical Research Council (UK). Additional support has been provided by the National Institute for Health Research Biomedical Research Centre in Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London.

Conflicts

AJP: none.

CMP: research funding from Janssen Pharmaceutical NV/Janssen Pharmaceutical Companies of Johnson & Johnson; speaker’s fees from Lundbeck and consultation fees from Eleusis Benefit Corporation.

PAZ: research funding from Janssen Pharmaceutical NV/Janssen Pharmaceutical Companies of Johnson & Johnson.

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Perrin, A.J., Pariante, C.M., Zunszain, P.A. (2020). Intergenerational Aspects of Immune and Endocrine Function in Perinatal Depression. In: Teixeira, A.L., Macedo, D., Baune, B.T. (eds) Perinatal Inflammation and Adult Psychopathology. Progress in Inflammation Research, vol 84. Springer, Cham. https://doi.org/10.1007/978-3-030-39335-9_5

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