Abstract
Mental illness during pregnancy and the postpartum period is a growing health crisis. We know that at least 1 in 7 women during the perinatal period will experience a mood or anxiety disorder such as perinatal depression (PND) or general anxiety disorder. These mental illnesses significantly impact the well-being of the mother, as well as how she interacts with her infant and family. Over the past 10 years there has been a growing need to understand the neuroendocrine mechanisms mediating perinatal mental illness. Much of this research has focused on aspects of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes and thus this chapter will focus on these two systems in perinatal mental illness. This chapter will review our current understanding of the neuroendocrinology of perinatal mental illness from research in women and animal models, with a focus on PND and anxiety, but will also consider the limited data we have for other perinatal mental illnesses such as postpartum psychosis and childbirth-related post-traumatic stress disorder. We have much research to do to fully understand the mechanisms behind these disorders and will discuss options for future research. Increased understanding of the unique neuroendocrine profiles associated with perinatal mental illness will allow us to predict risk, develop effective treatments and, ultimately, prevent suffering for millions of mothers during this critical time in life.
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References
Aktar E, Jin Q, Lawrence PJ, Tollenaar MS, Elzinga BM, Bögels SM (2019) Fetal and infant outcomes in the offspring of parents with perinatal mental disorders: earliest influences. Front Psychiatry/Front Res Found 10(June):391
Asher I, Kaplan B, Modai I, Neri A, Valevski A, Weizman A (1995) Mood and hormonal changes during late pregnancy and puerperium. Clin Exp Obstet Gynecol 22(4):321–325
Ayers S, Wright DB, Thornton A (2018) Development of a measure of postpartum PTSD: the city birth trauma scale. Front Psychiatry/Front Res Found 9(September):409
Bangasser DA, Valentino RJ (2014) Sex differences in stress-related psychiatric disorders: neurobiological perspectives. Front Neuroendocrinol 35:303–319
Bauer A, Pawlby S, Plant DT, King D, Pariante CM, Knapp M (2015) Perinatal depression and child development: exploring the economic consequences from a South London Cohort. Psychol Med 45(1):51–61
Bitran D, Solano SM (2005) Termination of pseudopregnancy in the rat alters the response to progesterone, chlordiazepoxide, and MK-801 in the elevated plus-Maze. Psychopharmacology 180(3):447–454
Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR (2000) Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry 157(6). https://doi.org/10.1176/appi.ajp.157.6.924
Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G (2005) Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab 90(2):695–699
Brummelte S, Pawluski JL, Galea LAM (2006) High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: a model of post-partum stress and possible depression. Horm Behav 50(3):370–382
de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475
Deligiannidis KM, Kroll-Desrosiers AR, Mo S, Nguyen HP, Svenson A, Jaitly N, Hall JE, Barton BA, Rothschild AJ, Shaffer SA (2016) Peripartum neuroactive steroid and γ-aminobutyric acid profiles in women at-risk for postpartum depression. Psychoneuroendocrinology 70(August):98–107
Dickens MJ, Pawluski JL (2018) The HPA axis during the perinatal period: implications for perinatal depression. Endocrinology 159(11):3737–3746
Dickens MJ, Pawluski JL, Michael Romero L (2020) Moving forward from COVID-19: bridging knowledge gaps in maternal health with a new conceptual model. Front Glob Women’s Health 1(November). https://doi.org/10.3389/fgwh.2020.586697
Doornbos B, Fokkema DS, Molhoek M, Tanke MAC, Postema F, Korf J (2009) Abrupt rather than gradual hormonal changes induce postpartum blues-like behavior in rats. Life Sci 84(3-4):69–74
Galea LA, Wide JK, Paine TA, Holmes MM, Ormerod BK, Floresco SB (2001) High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory. Behav Brain Res 126(1–2):115–126
Gemmel M, Harmeyer D, Bögi E, Fillet M, Hill LA, Hammond GL, Charlier TD, Pawluski JL (2018) Perinatal fluoxetine increases hippocampal neurogenesis and reverses the lasting effects of pre-gestational stress on serum corticosterone, but not on maternal behavior, in the rat dam. Behav Brain Res 339(February):222–231
Glasper ER, Kenkel WM, Bick J, Rilling JK (2019) More than just mothers: the neurobiological and neuroendocrine underpinnings of allomaternal caregiving. Front Neuroendocrinol 53:100741
Green AD, Galea LAM (2008) Adult hippocampal cell proliferation is suppressed with estrogen withdrawal after a hormone-simulated pregnancy. Horm Behav 54(1):203–211
Grigoriadis S, Wilton AS, Kurdyak PA, Rhodes AE, VonderPorten EH, Levitt A, Cheung A, Vigod SN (2017) Perinatal suicide in Ontario, Canada: a 15-year population-based study. Can Med Assoc J = Journal de l’Association Medicale Canadienne 189(34):E1085–E1092
Haim A, Julian D, Albin-Brooks C, Brothers HM, Lenz KM, Leuner B (2017) A survey of neuroimmune changes in pregnant and postpartum female rats. Brain Behav Immun 59(January):67–78
Hammond GL (2016) Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol 230:R13–R25
Hazelgrove K, Biaggi A, Waites F, Fuste M, Osborne S, Conroy S, Howard LM et al (2021) Risk factors for postpartum relapse in women at risk of postpartum psychosis: the role of psychosocial stress and the biological stress system. Psychoneuroendocrinology 128(April):105218
Hedges VL, Heaton EC, Amaral C, Benedetto LE, Bodie CL, D’Antonio BI, Davila Portillo DR et al (2021) Estrogen withdrawal increases postpartum anxiety via oxytocin plasticity in the paraventricular hypothalamus and dorsal raphe nucleus. Biol Psychiatry 89(9):929–938
Iliadis SI, Sylven S, Hellgren C, Olivier JD, Schijven D, Comasco E, Chrousos GP, Sundstrom Poromaa I, Skalkidou A (2016) Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms. Depress Anxiety 33:1023–1030
Kim P, Swain JE (2007) Sad dads: paternal postpartum depression. Psychiatry (Edgmont) 4:35–47
Kim P, Rigo P, Mayes LC, Feldman R, Leckman JF, Swain JE (2014) Neural plasticity in fathers of human infants. Soc Neurosci 9(5):522–35. https://doi.org/10.1080/17470919.2014.933713
Klampfl SM, Bosch OJ (2019) Mom doesn’t care: when increased brain CRF system activity leads to maternal neglect in rodents. Front Neuroendocrinol 53(April):100735
Kroll-Desrosiers AR, Nephew BC, Babb JA, Guilarte-Walker Y, Moore TA, Simas, and Kristina M. Deligiannidis. (2017) Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year. Depress Anxiety 34(2):137–146
Larsen CM, Grattan DR (2010) Prolactin-induced mitogenesis in the subventricular zone of the maternal brain during early pregnancy is essential for normal postpartum behavioral responses in the mother. Endocrinology 151(8):3805–3814
Laurent H, Goodman SH, Stowe ZN, Halperin M, Khan F, Wright D, Nelson BW et al (2018) Course of ante- and postnatal depressive symptoms related to mothers’ HPA axis regulation. J Abnormal Psychol. https://doi.org/10.1037/abn0000348
Lefevre A, Mottolese R, Dirheimer M, Mottolese C, Duhamel J-R, Sirigu A (2017) A comparison of methods to measure central and peripheral oxytocin concentrations in human and non-human primates. Sci Rep 7(1):17222
Leiferman JA, Farewell CV, Jewell J, Rachael L, Walls J, Harnke B, Paulson JF (2021) Anxiety among fathers during the prenatal and postpartum period: a meta-analysis. J Psychosom Obstet Gynaecol 42:152–161
Li M, Chou SY (2016) Modeling postpartum depression in rats: theoretic and methodological issues. Dongwuxue Yanjiu 37:229–236
Licheri V, Talani G, Gorule AA, Mostallino MC, Biggio G, Sanna E (2015) Plasticity of GABAA Receptors during Pregnancy and Postpartum Period: From Gene to Function. Neural Plast. 170435. https://doi.org/10.1155/2015/170435
Lindahl V, Pearson JL, Colpe L (2005) Prevalence of suicidality during pregnancy and the postpartum. Arch Womens Ment Health 8(2):77–87
Liu MY, Yin CY, Zhu LJ, Zhu XH, Xu C, Luo CX, Chen H, Zhu DY, Zhou QG (2018) Sucrose preference test for measurement of stress-induced anhedonia in mice. Nat Protoc 13:1686–1698
Magiakou MA, Mastorakos G, Rabin D, Dubbert B, Gold PW, Chrousos GP (1996) Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time. J Clin Endocrinol Metab 81(5):1912–1917
Maguire J (2019) Neuroactive steroids and GABAergic involvement in the neuroendocrine dysfunction associated with major depressive disorder and postpartum depression. Front Cell Neurosci 13(March):83
Maguire J, Mody I (2016) Behavioral Deficits in Juveniles Mediated by Maternal Stress Hormones in Mice. Neural Plast. 2762518. https://doi.org/10.1155/2016/2762518
Maguire J, Mody I (2008) GABA(A)R plasticity during pregnancy: relevance to postpartum depression. Neuron 59(2):207–213
Maguire JL, Stell BM, Rafizadeh M, Mody I (2005) Ovarian cycle-linked changes in GABA(A) receptors mediating tonicinhibition alter seizure susceptibility and anxiety. Nat Neurosci 8(6):797–804
Mahenge B, Stöckl H, Mizinduko M, Mazalale J, Jahn A (2018) Adverse childhood experiences and intimate partner violence during pregnancy and their association to postpartum depression. J Affect Disord. https://doi.org/10.1016/j.jad.2017.12.036
Masters GA, Asipenko E, Bergman AL, Person SD, Brenckle L, Moore TA, Simas JY, Ko CL, Robbins, and Nancy Byatt. (2021) Impact of the COVID-19 pandemic on mental health, access to care, and health disparities in the perinatal period. J Psychiatr Res 137(May):126–130
Melón LC, Hooper A, Yang X, Moss SJ, Maguire J (2018) Inability to suppress the stress-induced activation of the HPA Axis during the peripartum period engenders deficits in postpartum behaviors in mice. Psychoneuroendocrinology 90(April):182–193
Meltzer-Brody S, Kanes SJ (2020) Allopregnanolone in postpartum depression: role in pathophysiology and treatment. Neurobiol Stress 12(May):100212
Meltzer-Brody S, Colquhoun H, Robert Riesenberg C, Epperson N, Deligiannidis KM, Rubinow DR, Li H et al (2018) Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet 392(10152):1058–1070
Moses-Kolko EL, Horner MS, Phillips ML, Hipwell AE, Swain JE (2014) In search of neural endophenotypes of postpartum psychopathology and disrupted maternal caregiving. J Neuroendocrinol 26(10):665–684
Murgatroyd CA, Peña CJ, Podda G, Nestler EJ, Nephew BC (2015) Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care. Neuropeptides 52(August):103–111
Murray L, Cooper PJ (1997) Effects of postnatal depression on infant development. Arch Dis Child. https://doi.org/10.1136/adc.77.2.99
Numan M (2020) The parental brain: mechanisms, development, and evolution. Oxford University Press
Oberlander TF, Zwaigenbaum L (2017) Disentangling maternal depression and antidepressant use during pregnancy as risks for autism in children. JAMA 317:1533–1534
Oberlander TF, Gingrich JA, Ansorge MS (2009) Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: molecular to clinical evidence. Clin Pharmacol Ther 86:672–677
Osborne LM, Betz JF, Yenokyan G, Standeven LR, Payne JL (2019) The role of allopregnanolone in pregnancy in predicting postpartum anxiety symptoms. Front Psychol 10(July):1033
Pawluski JL, Brain UM, Underhill CM, Hammond GL, Oberlander TF (2012) Prenatal SSRI exposure alters neonatal corticosteroid binding globulin, infant cortisol levels, and emerging HPA function. Psychoneuroendocrinology 37(7):1019–1028
Pawluski JL, Lambert KG, Kinsley CH (2016) Neuroplasticity in the maternal hippocampus: Relation to cognition and effects ofrepeated stress. Horm Behav 77:86–97. https://doi.org/10.1016/j.yhbeh.2015.06.004
Pawluski JL, Lonstein JS, Fleming AS (2017) The neurobiology of postpartum anxiety and depression. Trends Neurosci 40(2):106–120
Pawluski JL, Li M, Lonstein JS (2019) Serotonin and motherhood: from molecules to mood. Front Neuroendocrinol 53:100742
Payne JL, Maguire J (2019) Pathophysiological mechanisms implicated in postpartum depression. Front Neuroendocrinol. https://doi.org/10.1016/j.yfrne.2018.12.001
Peled-Avron L, Abu-Akel A, Shamay-Tsoory S (2020) Exogenous effects of oxytocin in five psychiatric disorders: a systematic review, meta-analyses and a personalized approach through the lens of the social salience hypothesis. Neurosci Biobehav Rev 114(July):70–95
Post C, Leuner B (2019) The maternal reward system in postpartum depression. Arch Womens Ment Health 22(3):417–429
Qiu W, Hodges TE, Clark EL, Blankers SA, Galea LAM (2020) Perinatal depression: heterogeneity of disease and in animal models. Front Neuroendocrinol 59 (October):100854. Psychoneuroendocrinology 101 (March). https://doi.org/10.1016/j.psyneuen.2018.11.006
Ramdas DL, Sbrilli MD, Laurent HK (2021) Impact of maternal trauma-related psychopathology and life stress on HPA axis stress response. Arch Womens Ment Health
Rao WW, Zhu XM, Zong QQ, Zhang Q, Hall BJ, Ungvari GS, Xiang YT (2020) Prevalence of prenatal and postpartum depression in fathers: a comprehensive meta-analysis of observational surveys. J AffectDisord 263:491–499
Rich-Edwards J, Hacker M, Gillman M (2009) Premature recommendation of corticotropin-releasing hormone as screen for postpartum depression. Arch Gen Psychiatry
Riecher-Rössler A, Steiner M (2005) Perinatal stress, mood and anxiety disorders: from bench to bedside. Karger Medical and Scientific Publishers
Sambataro F, Cattarinussi G, Lawrence A, Biaggi A, Fusté M, Hazelgrove K, Mehta MA et al (2021) Altered dynamics of the prefrontal networks are associated with the risk for postpartum psychosis: a functional magnetic resonance imaging study. Transl Psychiatry 11(1):238
Saxbe DE, Schetter CD, Simon CD, Adam EK, Shalowitz MU (2017) High paternal testosterone may protect against postpartum depressive symptoms in fathers, but confer risk to mothers and children. Horm Behav 95(September):103–112
Saxbe D, Khaled M, Horton KT, Mendez AJ (2019) Maternal prenatal plasma oxytocin is positively associated with prenatal psychological symptoms, but method of immunoassay extraction may affect results. Biol Psychol 147(October):107718
Schiller CE, Johnson SL, Abate AC, Schmidt PJ, Rubinow DR (2016) Reproductive steroid regulation of mood and behavior. Compr Physiol. https://doi.org/10.1002/cphy.c150014
Seibenhener ML, Wooten MC (2015) Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp JoVE:e52434
Seth S, Lewis AJ, Galbally M (2016) Perinatal maternal depression and cortisol function in pregnancy and the postpartum period: a systematic literature review. BMC Pregnancy Childbirth 16(1):124
Skrundz, Marta, Margarete Bolten, Irina Nast, Dirk H. Hellhammer, and Gunther Meinlschmidt. 2011. “Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression.” Neuropsychopharmacology 36(9): 1886–1893.
Slattery DA, Cryan JF (2012) Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc 7:1009–1014
Suda S, Segi-Nishida E, Newton SS, Duman RS (2008) A postpartum model in rat: behavioral and gene expression changes induced by ovarian steroid deprivation. Biol Psychiatry 64(4):311–319
Swaab DF, Bao A-M, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4(2):141–194
Szpunar MJ, Parry BL (2018) A systematic review of cortisol, thyroid-stimulating hormone, and prolactin in peripartum women with major depression. Arch Womens Ment Health 21(2):149–161. https://doi.org/10.1007/s00737-017-0787-9
Thorsness KR, Watson C, LaRusso EM (2018) Perinatal anxiety: approach to diagnosis and management in the obstetric setting. Am J Obstet Gynecol 219:326–345
Thul TA, Corwin EJ, Carlson NS, Brennan PA, Young LJ (2020) Oxytocin and postpartum depression: a systematic review. Psychoneuroendocrinology 120(October):104793
Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2:322–328
Walton N, Maguire J (2019) Allopregnanolone-based treatments for postpartum depression: why/how do they work? Neurobiol Stress 11(November):100198
Wang T, Shi C, Li X, Zhang P, Liu B, Wang H, Wang Y et al (2018) Injection of oxytocin into paraventricular nucleus reverses depressive-like behaviors in the postpartum depression rat model. Behav Brain Res 336(January):236–243
Wang J, Yun Q, Ma SF, Song HR, Guo MN, Zhang WN (2020) Inhibition of expression of glucocorticoids receptors maycontribute to postpartum depression. Biochem Biophys Res Commun 26;523(1):159–164. https://doi.org/10.1016/j.bbrc.2019.12.040
Weigl T, Schneider N, Stein A, Felderhoff-Müser U, Schedlowski M, Engler H (2020) Postpartal affective and endocrine differences between parents of preterm and full-term infants. Front Psychiatry/Front Res Foundation 11. https://doi.org/10.3389/fpsyt.2020.00251
Witteveen AB, Stramrood CAI, Henrichs J, Flanagan JC, van Pampus MG, Olff M (2020) The oxytocinergic system in PTSD following traumatic childbirth: endogenous and exogenous oxytocin in the peripartum period. Arch Womens Ment Health 23(3):317–329
Yim IS, Glynn LM, Dunkel-Schetter C, Hobel CJ, Chicz-DeMet A, Sandman CA (2009) Risk of postpartum depressive symptoms with elevated corticotropin-releasing hormone in human pregnancy. Arch Gen Psychiatry 66(2):162–169
Zhang Z, Hong J, Zhang S, Zhang T, Sha S, Yang R, Qian Y, Chen L (2016) Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice. Psychoneuroendocrinology 66(April):138–149
Zoubovsky SP, Hoseus S, Tumukuntala S, Schulkin JO, Williams MT, Vorhees CV, Muglia LJ (2020) Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression. Transl Psychiatry 10(1):6
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Pawluski, J., Dickens, M., Maguire, J. (2024). Neuroendocrinology of Perinatal Mental Illness. In: Brunton, P.J., Grattan, D.R. (eds) Neuroendocrine Regulation of Mammalian Pregnancy and Lactation. Masterclass in Neuroendocrinology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-031-51138-7_10
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