Skip to main content

Advertisement

SpringerLink
Log in

The dynamic serotonin system of the maternal brain

  • Original Article
  • Published:
Archives of Women's Mental Health Aims and scope Submit manuscript

Abstract

Many pregnant and postpartum women worldwide suffer from high anxiety and/or depression, which can have detrimental effects on maternal and infant well-being. The first-line pharmacotherapies for prepartum and postpartum affective disorders continue to be the selective serotonin reuptake inhibitors (SSRIs), despite the lack of large well-controlled studies demonstrating their efficacy in reproducing women and the potential for fetal/neonatal exposure to the drugs. Prepartum or postpartum use of SSRIs or other drugs that modulate the brain’s serotonin system is also troubling because very little is known about the typical, let alone the atypical, changes that occur in the female central serotonin system across reproduction. We do know from a handful of studies of women and female laboratory rodents that numerous aspects of the central serotonin system are naturally dynamic across reproduction and are also affected by pregnancy stress (a major predisposing factor for maternal psychopathology). Thus, it should not be assumed that the maternal central serotonin system being targeted by SSRIs is identical to non-parous females or males. More information about the normative and stress-derailed changes in the maternal central serotonin system is essential for understanding how serotonin is involved in the etiology of, and the best use of SSRIs for potentially treating, affective disorders in the pregnant and postpartum populations.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adachi M, Autry AE, Mahgoub M, Suzuki K, Monteggia LM (2017) TrkB signaling in dorsal raphe nucleus is essential for antidepressant efficacy and normal aggression behavior. Neuropsychopharmacology 42(4):886–894

    Article  CAS  PubMed  Google Scholar 

  • Akbari EM, Chatterjee D, Lévy F, Fleming AS (2007) Experience-dependent cell survival in the maternal rat brain. Behav Neurosci 121(5):1001–1011

    Article  PubMed  Google Scholar 

  • Alwan S, Reefhuis J, Rasmussen SA, Friedman JM, National Birth Defects Prevention Study (2011) Patterns of antidepressant medication use among pregnant women in a United States population. J Clin Pharmacol 51(2):264–270

  • Anderson GD (2006) Using pharmacokinetics to predict the effects of pregnancy and maternal-infant transfer of drugs during lactation. Exp Opin Drug Metabol Toxicol 2(6):947–960

    Article  CAS  Google Scholar 

  • Andrade SE, Raebel MA, Brown J, Lane K, Livingston J, Boudreau D, Rolnick SJ, Roblin D, Smith DH, Dal Pan GJ, Scott PE, Platt R (2008) Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol 198(2):194 e191–195

  • Appleby L (1998) Violent suicide and obstetric complications The link is mental illness. Br Med J 317(7169):1333–1334

    Article  CAS  Google Scholar 

  • Arenas E, Denham M, Villaescusa JC (2015) How to make a midbrain dopaminergic neuron. Development 142(11):1918–1936

    Article  CAS  PubMed  Google Scholar 

  • Badawy AA (2014) The tryptophan utilization concept in pregnancy. Obstet Gynecol Sci 57(4):249–259

    Article  PubMed  PubMed Central  Google Scholar 

  • Bérard A, Gaedigk A, Sheehy O, Chambers C, Roth M, Bozzo P, Johnson D, Kao K, Lavigne S, Wolfe L, Quinn D, Dieter K, Zhao JP, OTIS (MotherToBaby) Collaborative Research Committee (2017) Association between CYP2D6 genotypes and the risk of antidepressant discontinuation, dosage modification and the occurrence of maternal depression during pregnancy. Front Pharmacol 17(8):402

    Article  CAS  Google Scholar 

  • Bethea CL, Lu NZ, Gundlah C, Streicher JM (2002) Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol 23:41–100

    Article  CAS  PubMed  Google Scholar 

  • Bethea CL, Phu K, Reddy AP, Cameron JL (2013) The effect of short-term stress on serotonin gene expression in high and low resilient macaques. Prog Neuro-Psychopharmacol Biol Psychiat 44:143–153

    Article  CAS  Google Scholar 

  • Boothman L, Raley J, Denk F, Hirani E, Sharp T (2006) In vivo evidence that 5-HT(2C) receptors inhibit 5-HT neuronal activity via a GABAergic mechanism. Br J Pharmacol 149(7):861–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Britton JR (2008) Maternal anxiety: course and antecedents during the early postpartum period. Depress Anx 25(9):793–800

    Article  Google Scholar 

  • Brunton PJ, Russell JA, Douglas AJ (2008) Adaptive responses of the maternal hypothalamic-pituitary-adrenal axis during pregnancy and lactation. J Neuroendocrinol 20(6):764–776

    Article  CAS  PubMed  Google Scholar 

  • Charlton RA, Jordan S, Pierini A, Garne E, Neville AJ, Hansen AV, Gini R, Thayer D, Tingay K, Puccini A, Bos HJ, Nybo Andersen AM, Sinclair M, Dolk H, de Jong-van den Berg LT (2015) Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based study in six European regions. Brit J Obstet Gynaecol 122(7):1010–1020

  • Chavez C, Hollaus M, Scarr E, Pavey G, Gogos A, van den Buuse M (2010) The effect of estrogen on dopamine and serotonin receptor and transporter levels in the brain: an autoradiography study. Brain Res 1321:51–59

    Article  CAS  PubMed  Google Scholar 

  • Chechik G, Meilijson I, Ruppin E (1999) Neuronal regulation: a mechanism for synaptic pruning during brain maturation. Neural Comput 11(8):2061–2080

    Article  CAS  PubMed  Google Scholar 

  • Chesney E, Goodwin GM, Fazel S (2014) Risks of all-cause and suicide mortality in mental disorders: a meta-review. World Psychiat 13(2):153–160

    Article  Google Scholar 

  • Committee on Obstetric Practice (2015) The American College of Obstetricians and Gynecologists Committee Opinion no. 630. Screening for perinatal depression. Obstet Gynecol 125(5):1268–1271

  • Corona R, Meurisse M, Cornilleau F, Moussu C, Keller M, Lévy F (2017) Exposure to young preferentially activates adult-born neurons in the main olfactory bulb of sheep mothers. Brain Struct Funct 222(3):1219–1229

    Article  CAS  PubMed  Google Scholar 

  • Costas J, Gratacos M, Escaramis G, Martín-Santos R, de Diego Y, Baca-García E, Canellas F, Estivill X, Guillamat R, Guitart M, Gutiérrez-Zotes A, García-Esteve L, Mayoral F, Moltó MD, Phillips C, Roca M, Carracedo A, Vilella E, Sanjuán J (2010) Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women. J Psychiat Res 44(11):717–724

  • De Crescenzo F, Perelli F, Armando M, Vicari S (2014) Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials. J Affect Disord 152-154:39–44

    Article  CAS  PubMed  Google Scholar 

  • Darnaudery M, Dutriez I, Viltart O, Morley-Fletcher S, Maccari S (2004) Stress during gestation induces lasting effects on emotional reactivity of the dam rat. Behav Brain Res 153(1):211–216

    Article  PubMed  Google Scholar 

  • Davé S, Petersen I, Sherr L, Nazareth I (2010) Incidence of maternal and paternal depression in primary care: a cohort study using a primary care database. Arch Pediatr Adolesc Med 164(11):1038–1044

    Article  PubMed  Google Scholar 

  • Desan PH, Woodmansee WW, Ryan SM, Smock TK, Maier SF (1988) Monoamine neurotransmitters and metabolites during the estrous cycle, pregnancy, and the postpartum period. Pharmacol Biochem Behav 30(3):563–568

    Article  CAS  PubMed  Google Scholar 

  • Donner N, Handa RJ (2009) Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within serotonergic neurons of the rat dorsal raphe nuclei. Neuroscience 163(2):705–718

    Article  CAS  PubMed  Google Scholar 

  • Drury SS, Scaramella L, Zeanah CH (2016) The neurobiological impact of postpartum maternal depression: prevention and intervention approaches. Child Adol Psych 25(2):179–200

    Google Scholar 

  • Fairbrother N, Janssen P, Antony MM, Tucker E, Young AH (2016) Perinatal anxiety disorder prevalence and incidence. J Affect Disord 200:148–155

    Article  PubMed  Google Scholar 

  • Fernstrom JD, Wurtman RJ (1971) Brain serotonin content: physiological dependence on plasma tryptophan levels. Science 173(3992):149–152

    Article  CAS  PubMed  Google Scholar 

  • Fernstrom JD, Wurtman RJ (1972) Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178(4059):414–416

    Article  CAS  PubMed  Google Scholar 

  • Field T (2010) Postpartum depression effects on early interactions, parenting, and safety practices: a review. Inf Behav Dev 33(1):1–6

    Article  Google Scholar 

  • Fox JH, Lowry CA (2013) Corticotropin-releasing factor-related peptides, serotonergic systems, and emotional behavior. Front Neurosci 7:169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freeman MP, Nolan PE, Davis MF, Anthony M, Fried K, Fankhauser M, Woosley RL, Moreno F (2008) Pharmacokinetics of sertraline across pregnancy and postpartum. J Clin Psychopharmacol 28(6):646–653

    Article  CAS  PubMed  Google Scholar 

  • Fink G, Sumner BE, Rosie R, Grace O, Quinn JP (1996) Estrogen control of central neurotransmission: Effect on mood, mental state, and memory. Cell Mol Neurobiol 16(3):325–344

  • Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC (2018) Neuronal cell death. Physiol Rev 98(2):813–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furuta M, Bridges RS (2005) Gestation-induced cell proliferation in the rat brain. Brain Res Dev Brain Res 156(1):61–6

  • Galea LA, Leuner B, Slattery DA (2014) Hippocampal plasticity during the peripartum period: influence of sex steroids stress and ageing. J Neuroendocrinol 26(10):641–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gammie SC, Driessen TM, Zhao C, Saul MC, Eisinger BE (2016) Genetic and neuroendocrine regulation of the postpartum brain. Front Neuroendocrinol 42:1–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gemmel M, Rayen I, van Donkelaar E, Loftus T, Steinbusch HW, Kokras N, Dalla C, Pawluski JL (2016) Gestational stress and fluoxetine treatment differentially affect plasticity, methylation and serotonin levels in the PFC and hippocampus of rat dams. Neuroscience 327:32–43

  • Glaser J, Russell VA, de Villiers AS, Searson JA, Taljaard JJ (1990) Rat brain monoamine and serotonin S2 receptor changes during pregnancy. Neurochem Res 15(10):949–956

    Article  CAS  PubMed  Google Scholar 

  • Glasheen C, Richardson GA, Fabio A (2010) A systematic review of the effects of postnatal maternal anxiety on children. Arch Women’s Mental Health 13(1):61–74

    Article  Google Scholar 

  • Glover ME, Clinton SM (2016) Of rodents and humans: a comparative review of the neurobehavioral effects of early life SSRI exposure in preclinical and clinical research. Int J Dev Neurosci 51:50–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goodman JH, Watson GR, Stubbs B (2016) Anxiety disorders in postpartum women: a systematic review and meta-analysis. J Affect Disord 203:292–331

    Article  PubMed  Google Scholar 

  • Haase J, Brown E (2015) Integrating the monoamine, neurotrophin and cytokine hypotheses of depression—a central role for the serotonin transporter? Pharmacol Therap 147:1–11

    Article  CAS  Google Scholar 

  • Haim A, Sherer M, Leuner B (2014) Gestational stress induces persistent depressive-like behavior and structural modifications within the postpartum nucleus accumbens. Eur J Neurosci 40(12):3766–3773

    Article  PubMed  PubMed Central  Google Scholar 

  • Handley SL, Dunn TL, Waldron G, Baker JM (1980) Tryptophan, cortisol and puerperal mood. British J Psychiatry 136:498–508

    Article  CAS  Google Scholar 

  • Hanley GE, Mintzes B (2014) Patterns of psychotropic medicine use in pregnancy in the United States from 2006 to 2011 among women with private insurance. BMC Preg Childbirth 14:242

    Article  Google Scholar 

  • Harding KM, Lonstein JS (2016) Extensive juvenile “babysitting” facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase-2 expression in female laboratory rats. Dev Psychobiol 58(4):492–508

    Article  CAS  PubMed  Google Scholar 

  • Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K (2002) Citalopram in pregnancy and lactation. Clin Pharmacol Ther 72(2):184–191

    Article  CAS  PubMed  Google Scholar 

  • Hillerer KM, Reber SO, Neumann ID, Slattery DA (2011) Exposure to chronic pregnancy stress reverses peripartum-associated adaptations: implications for postpartum anxiety and mood disorders. Endocrinology 152(10):3930–3940

    Article  CAS  PubMed  Google Scholar 

  • Holmes A, Yang RJ, Murphy DL, Crawley JN (2002) Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 27(6):914–923

    Article  CAS  PubMed  Google Scholar 

  • Holschbach MA, Lonstein JS (2016) Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe. Psychoneuroendocrinology 76:97–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horne MK, Lee J, Chen F, Lanning K, Tomas D, Lawrence AJ (2008) Long-term administration of cocaine or serotonin reuptake inhibitors results in anatomical and neurochemical changes in noradrenergic, dopaminergic, and serotonin pathways. J Neurochem 106(4):1731–1744

    CAS  PubMed  Google Scholar 

  • Hostetter A, Stowe ZN, Strader JR Jr, McLaughlin E, Llewellyn A (2000) Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications. Depress Anx 11(2):51–57

    Article  CAS  Google Scholar 

  • Huybrechts KF, Palmsten K, Mogun H, Kowal M, Avorn J, Setoguchi-Iwata S, Hernández-Díaz S (2013) National trends in antidepressant medication treatment among publicly insured pregnant women. Gen Hosp Psych 35(3):265–271

  • Inagaki T, Gautreaux C, Luine V (2010) Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm Behav 58(3):415–426

  • Jury NJ, McCormick BA, Horseman ND, Benoit SC, Gregerson KA (2015) Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation. PLoS One 10(2):e0117339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalueff AV, Fox MA, Gallagher PS, Murphy DL (2007) Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice. Genes Brain Behav 6(4):389–400

    Article  CAS  PubMed  Google Scholar 

  • Kim P, Strathearn L, Swain JE (2016) The maternal brain and its plasticity in humans. Horm Behav 77:113–123

  • Klink R, Robichaud M, Debonnel G (2002) Gender and gonadal status modulation of dorsal raphe nucleus serotonergic neurons. Part I: effects of gender and pregnancy. Neuropharmacology 43(7):1119–1128

    Article  CAS  PubMed  Google Scholar 

  • Lancaster CA, Gold KJ, Flynn HA, Yoo H, Marcus SM, Davis MM (2010) Risk factors for depressive symptoms during pregnancy: a systematic review. Amer J Obstet Gynecol 202(1):5–14

    Article  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Le Strat Y, Dubertret C, Le Foll B (2011) Prevalence and correlates of major depressive episode in pregnant and postpartum women in the United States. J Affect Disord 135(1–3):128–138

    Article  PubMed  Google Scholar 

  • Leuner B, Sabihi S (2016) The birth of new neurons in the maternal brain: hormonal regulation and functional implications. Front Neuroendocrinol 41:99–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leuner B, Fredericks PJ, Nealer C, Albin-Brooks C (2014) Chronic gestational stress leads to depressive-like behavior and compromises medial prefrontal cortex structure and function during the postpartum period. PLoS One 9(3):e89912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lévy F, Batailler M, Meurisse M, Migaud M (2017) Adult neurogenesis in sheep: characterization and contribution to reproduction and behavior. Front Neurosci 11:570

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Y, Luikart BW, Birnbaum S et al (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59(3):399–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lira A, Zhou M, Castanon N, Ansorge MS, Gordon JA, Francis JH, Bradley-Moore M, Lira J, Underwood MD, Arango V, Kung HF, Hofer MA, Hen R, Gingrich JA (2003) Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporter-deficient mice. Biol Psychiatry 54(10):960–971

    Article  CAS  PubMed  Google Scholar 

  • Lonstein JS, Dominguez JM, Putnam SK, De Vries GJ, Hull EM (2003) Intracellular preoptic and striatal monoamines in pregnant and lactating rats: possible role in maternal behavior. Brain Res 970(1–2):149–158

    Article  CAS  PubMed  Google Scholar 

  • Lowry CA, Evans AK, Gasser PJ, Hale MW, Staub DR, Shekhar A (2008) Topographic organization and chemoarchitecture of the dorsal raphe nucleus and the median raphe nucleus. In: Monti JM, Pandi-Perumal SR, Jacobs BL, Nutt DJ (eds) Serotonin and sleep: molecular, functional and clinical aspects. Birkhäuser Verlag, Switzerland

    Google Scholar 

  • Lupattelli A, Spigset O, Twigg MJ, Zagorodnikova K, Mårdby AC, Moretti ME, Drozd M, Panchaud A, Hämeen-Anttila K, Rieutord A, Gjergja Juraski R, Odalovic M, Kennedy D, Rudolf G, Juch H, Passier A, Björnsdóttir I, Nordeng H (2014) Medication use in pregnancy: a cross-sectional, multinational web-based study. BMJ Open 4(2):e004365

  • Maes M, Verkerk R, Bonaccorso S, Ombelet W, Bosmans E, Scharpe S (2002) Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation. Life Sci 71(16):1837–1848

    Article  CAS  PubMed  Google Scholar 

  • Maghsoudi N, Ghasemi R, Ghaempanah Z, Ardekani AM, Nooshinfar E, Tahzibi A (2014) Effect of chronic restraint stress on HPA axis activity and expression of BDNF and Trkb in the hippocampus of pregnant rats: possible contribution in depression during pregnancy and postpartum period. Basic Clin Neurosci 5(2):131–137

    PubMed  PubMed Central  Google Scholar 

  • McDonagh MS, Matthews A, Phillipi C, Romm J, Peterson K, Thakurta S, Guise JM (2014) Depression drug treatment outcomes in pregnancy and the postpartum period: a systematic review and meta-analysis. Obstet Gynecol 124(3):526–534

  • Mehta D, Quast C, Fasching PA, Seifert A, Voigt F, Beckmann MW, Faschingbauer F, Burger P, Ekici AB, Kornhuber J, Binder EB, Goecke TW (2012) The 5-HTTLPR polymorphism modulates the influence on environmental stressors on peripartum depression symptoms. J Affect Disord 136(3):1192–1197

  • Miao Z, Mao F, Liang J, Szyf M, Wang Y, Sun ZS (2018) Anxiety-related behaviours associated with microRNA-206-3p and BDNF expression in pregnant female mice following psychological social stress. Mol Neurobiol 55(2):1097–1111

    Article  CAS  PubMed  Google Scholar 

  • Mitchell C, Notterman D, Brooks-Gunn J, Hobcraft J, Garfinkel I, Jaeger K, Kotenko I, McLanahan S (2011) Role of mother’s genes and environment in postpartum depression. Proc Nat Acad Sci USA 108(20):8189–8193

  • Molyneaux E, Trevillion K, Howard LM (2015) Antidepressant treatment for postnatal depression. JAMA 313(19):1965–1966

    Article  PubMed  Google Scholar 

  • Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T, Meuth S, Nagy A, Greene RW, Nestler EJ (2004) Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Nat Acad Sci USA 101(29):10827–10832

  • Munk-Olsen T, Gasse C, Laursen TM (2012) Prevalence of antidepressant use and contacts with psychiatrists and psychologists in pregnant and postpartum women. Acta Psych Scand 125(4):318–324

    Article  CAS  Google Scholar 

  • 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(6):672–677

    Article  CAS  PubMed  Google Scholar 

  • O'Connor E, Rossom RC, Henninger M, Groom HC, Burda BU (2016) Primary care screening for and treatment of depression in pregnant and postpartum women: evidence report and systematic review for the US Preventive Services Task Force. JAMA 315(4):388–406

    Article  CAS  PubMed  Google Scholar 

  • O'Hara MW, Zekoski EM, Philipps LH, Wright EJ (1990) Controlled prospective study of postpartum mood disorders: comparison of childbearing and nonchildbearing women. J Abnorm Psychol 99(1):3–15

    Article  CAS  PubMed  Google Scholar 

  • Olivier JD, Van Der Hart MG, Van Swelm RP, Dederen PJ, Homberg JR, Cremers T, Deen PM, Cuppen E, Cools AR, Ellenbroek BA (2008) A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Neuroscience 152(3):573–584

    Article  CAS  PubMed  Google Scholar 

  • O'Mahony SM, Myint AM, van den Hove D, Desbonnet L, Steinbusch H, Leonard BE (2006) Gestational stress leads to depressive-like behavioural and immunological changes in the rat. Neuroimmunomodulation 13(2):82–88

    Article  CAS  PubMed  Google Scholar 

  • Pariente G, Leibson T, Carls A, Adams-Webber T, Ito S, Koren G (2016) Pregnancy-associated changes in pharmacokinetics: a systematic review. PLoS Med 13(11):e1002160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pawluski JL, Galea LA (2007) Reproductive experience alters hippocampal neurogenesis during the postpartum period in the dam. Neuroscience 149(1):53–67

    Article  CAS  PubMed  Google Scholar 

  • Pawluski JL, van den Hove DL, Rayen I, Prickaerts J, Steinbusch HW (2011) Stress and the pregnant female: impact on hippocampal cell proliferation, but not affective-like behaviors. Horm Behav 59(4):572–580

    Article  PubMed  Google Scholar 

  • Pawluski JL, Charlier TD, Fillet M, Houbart V, Crispin HT, Steinbusch HW, van den Hove DL (2012a) Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam. Behav Brain Res 228(1):159–168

  • Pawluski JL, Valenca A, Santos AI, Costa-Nunes JP, Steinbusch HW, Strekalova T (2012b) Pregnancy or stress decrease complexity of CA3 pyramidal neurons in the hippocampus of adult female rats. Neuroscience 227:201–210

    Article  CAS  PubMed  Google Scholar 

  • Pereira M (2016) Structural and functional plasticity in the maternal brain circuitry. New Dir Child Adolesc Dev 2016(153):23–46

  • Pinheiro RT, Coelho FM, Silva RA, et al. (2013) Association of a serotonin transporter gene polymorphism (5-HTTLPR) and stressful life events with postpartum depressive symptoms: a population-based study. J Psychosomatic Obstet Gynaecol 34(1):29–33

  • Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33(1):88–109

    Article  CAS  PubMed  Google Scholar 

  • Reck C, Struben K, Backenstrass M et al (2008) Prevalence, onset and comorbidity of postpartum anxiety and depressive disorders. Acta Psychiat Scand 118(6):459–468

    Article  CAS  PubMed  Google Scholar 

  • Robertson E, Grace S, Wallington T, Stewart DE (2004) Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psych 26(4):289–295

    Article  Google Scholar 

  • Ruhé HG, Ooteman W, Booij J, Michel MC, Moeton M, Baas F, Schene AH (2009) Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder. Pharmacogenet Genomics 19(1):67–76

    Article  CAS  PubMed  Google Scholar 

  • Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, Agerman K, Haapasalo A, Nawa H, Aloyz R, Ernfors P, Castrén E (2003) Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci 23(1):349–357

  • Sekiyama T, Nakatani Y, Yu X, Seki Y, Sato-Suzuki I, Arita H (2013) Increased blood serotonin concentrations are correlated with reduced tension/anxiety in healthy postpartum lactating women. Psych Res 209(3):560–565

    Article  CAS  Google Scholar 

  • Serrats J, Mengod G, Cortés R (2005) Expression of serotonin 5-HT2C receptors in GABAergic cells of the anterior raphe nuclei. J Chem Neuroanat 29(2):83–91

    Article  CAS  PubMed  Google Scholar 

  • Serretti A, Kato M (2008) The serotonin transporter gene and effectiveness of SSRIs. Expert Rev Neurotherpeutics 8(1):111–120

    Article  Google Scholar 

  • Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S (2003) Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science 299(5603):117–120

    Article  CAS  PubMed  Google Scholar 

  • Sisk CL, Lonstein JS, Gore AC (2013) Hormonal influences on neurobehavioral transitions across the lifespan. In: Neuroscience in the 21st century: basic and clinical. Pfaff DW, Supervisory Editor (Neuroendocrinology). Springer Press, pp 1715–1752. https://doi.org/10.1007/978-1-4614-1997-6_61

  • Sit DK, Perel JM, Helsel JC, Wisner KL (2008) Changes in antidepressant metabolism and dosing across pregnancy and early postpartum. J Clin Psychiatry 69(4):652–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sit D, Perel JM, Luther JF, Wisniewski SR, Helsel JC, Wisner KL (2010) Disposition of chiral and racemic fluoxetine and norfluoxetine across childbearing. J Clin Psychopharmacol 30(4):381–6

  • Smith JW, Seckl JR, Evans AT, Costall B, Smythe JW (2004) Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats. Psychoneuroendocrinology 29(2):227–244

    Article  CAS  PubMed  Google Scholar 

  • Smith CD, Piasecki CC, Weera M, Olszewicz J, Lonstein JS (2013) Noradrenergic alpha-2 receptor modulators in the ventral bed nucleus of the stria terminalis: effects on anxiety behavior in postpartum and virgin female rats. Behav Neurosci 127(4):582–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soderquist J, Wijma B, Thorbert G, Wijma K (2009) Risk factors in pregnancy for post-traumatic stress and depression after childbirth. Brit J Obstet Gynaecol 116(5):672–680

    Article  CAS  Google Scholar 

  • Spielman FJ, Mueller RA, Corke BC (1985) Cerebrospinal fluid concentration of 5-hydroxyindoleactic acid in pregnancy. Anesthesiology 62(2):193–195

    Article  CAS  PubMed  Google Scholar 

  • Stein A, Pearson RM, Goodman SH, Rapa E, Rahman A, McCallum M, Howard LM, Pariante CM (2014) Effects of perinatal mental disorders on the fetus and child. Lancet 384(9956):1800–1819

  • Stetler C, Miller GE (2011) Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosomatic Med 73(2):114–126

  • Szewczyk B, Kotarska K, Daigle M, Misztak P, Sowa-Kucma M, Rafalo A, Curzytek K, Kubera M, Basta-Kaim A, Nowak G, Albert PR (2014) Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1. Int J Neuropsychopharmacol 17(11):1763–1775

  • Veen C, Myint AM, Burgerhout KM, Schwarz MJ, Schütze G, Kushner SA, Hoogendijk WJ, Drexhage HA, Bergink V (2016) Tryptophan pathway alterations in the postpartum period and in acute postpartum psychosis and depression. J Affect Dis 189:298–305

  • Ververs FF, Voorbij HA, Zwarts P, Belitser SV, Egberts TC, Visser GH, Schobben AF (2009) Effect of cytochrome P450 2D6 genotype on maternal paroxetine plasma concentrations during pregnancy. Clin Pharmacokinet 48(10):677–683

    Article  CAS  PubMed  Google Scholar 

  • Vitale EM, Washington CL, Lonstein JS (2017) Female reproductive state influences raphe and forebrain serotonin 1A, 2A, and 2C receptor expression. Soc Neurosci Abstr 782:04

  • Weisskopf E, Fischer CJ, Bickle Graz M, Morisod Harari M, Tolsa JF, Claris O, Vial Y, Eap CB, Csajka C, Panchaud A (2015) Risk-benefit balance assessment of SSRI antidepressant use during pregnancy and lactation based on best available evidence. Exp Opin Drug Safety 14(3):413–427

  • Westin AA, Brekke M, Molden E, Skogvoll E, Spigset O (2017) Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: changes in drug disposition. PLoS One 12(7):e0181082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Workman JL, Gobinath AR, Kitay NF, Chow C, Brummelte S, Galea LA (2016) Parity modifies the effects of fluoxetine and corticosterone on behavior, stress reactivity, and hippocampal neurogenesis. Neuropharmacology 105:443–453

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author would like to thank M. Allie Holschbach, Erika M. Vitale, Carl D. Smith, and Katie M. Harding for conducting the research from the author’s lab that was discussed in this review.

Funding

Some of the author’s research described herein was supported in part by NIH grants R01HD057962, NRSA F32MH099892, and NRSA F32MH83344.

Author information

Authors and Affiliations

  1. Department of Psychology & Neuroscience Program, Michigan State University, 108 Giltner Hall, East Lansing, MI, 48824, USA

    Joseph S. Lonstein

Authors
  1. Joseph S. Lonstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph S. Lonstein.

Ethics declarations

Conflict of interest

The author declares that there is no conflict of interest.

Ethical approval

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

Additional information

This article is part of the Topical Collection on Neurobiology of Maternal Mental Illness

Guest Editor: Jodi Pawluski

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lonstein, J.S. The dynamic serotonin system of the maternal brain. Arch Womens Ment Health 22, 237–243 (2019). https://doi.org/10.1007/s00737-018-0887-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00737-018-0887-1

Keywords

Search

Navigation