Abstract
Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved in adjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT during pregnancy and the development of PPD symptoms. A total of 74 healthy, pregnant women were included in this prospective study. During the third trimester of pregnancy and within 2 weeks after parturition, PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Blood samples for plasma OXT assessment were collected in the third trimester. Following the literature, participants with postpartum EPDS scores of 10 or more were regarded as being at risk for PPD development (rPPD group). In a logistic regression analysis, plasma OXT was included as a potential predictor for being at risk for PPD. Results were controlled for prepartal EPDS score, sociodemographic and birth-outcome variables. Plasma OXT concentration in mid-pregnancy significantly predicted PPD symptoms at 2 weeks postpartum. Compared with the no-risk-for-PPD group, the rPPD group was characterized by lower plasma OXT concentrations. To our knowledge, this is the first study to show an association between prepartal plasma OXT concentration and postpartal symptoms of PPD in humans. Assuming a causal relationship, enhancing OXT release during pregnancy could serve as a potential target in prepartum PPD prevention, and help to minimize adverse effects of PPD on the mother–child relationship.
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References
Beck CT (1995). The effects of postpartum depression on maternal-infant interaction: A meta-analysis. Nurs Res 44: 298–304.
Beck CT (2006). Postpartum depression. Am J Nurs 106: 40–50.
Bergant AM, Nguyen T, Heim K, Ulmer H, Dapunt O (1998). German version and validation of the Edinburgh postnatal depression scale (EPDS)). Deutsche Medizinische Wochenschrift 123: 35–40.
Bloch M, Daly RC, Rubinow DR (2003). Endocrine factors in the etiology of postpartum depression. Compr Psychiatry 44: 234–246.
Brummelte S, Galea LAM (2010). Depression during pregnancy and postpartum: Contribution of stress and ovarian hormones. Prog Neuro-Psychopharmacol Biol Psychiatry 34: 766–776.
Cooper PJ, Murray L (1998). Postnatal depression. Br Med J 316: 1884–1886.
DaCosta APC, GuevaraGuzman RG, Ohkura S, Goode JA, Kendrick KM (1996). The role of oxytocin release in the paraventricular nucleus in the control of maternal behaviour in the sheep. J Neuroendocrinol 8: 163–177.
Dawood MY, Ylikorkala O, Trivedi D, Fuchs F (1979). Oxytocin in maternal circulation and amniotic-fluid during pregnancy. J Clin Endocrinol Metabol 49: 429–434.
De Geest K, Thiery M, Piron-Possuyt G, Vanden Driessche R (1985). Plasma oxytocin in human pregnancy and parturition. J Perina Med 13: 3–13.
Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO (2001). Review of validation studies of the Edinburgh postnatal depression scale. Acta Psychiatrica Scandinavica 104: 243–249.
Ehlert U, Patalla U, Kirschbaum C, Piedmont E, Hellhammer DH (1990). Postpartum blues: salivary cortisol and psychological factors. J Psychosomat Res 34: 319–325.
Feldman R, Weller A, Zagoory-Sharon O, Levine A (2007). Evidence for a neuroendocrinological foundation of human affiliation - Plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding. Psychol Sci 18: 965–970.
Frasch A, Zetzsche T, Steiger A, Jirikowski GF (1995). Reduction of plasma oxytocin levels in patients suffering from major depression. In: Ivell R, Russell JA (eds). Oxytocin—Cellular and Molecular Approaches in Medicine and Research. Plenum Press Div Plenum Publishing Corp: New York. Vol 395, pp 257–258.
Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T (2005). Perinatal depression—A systematic review of prevalence and incidence. Obstetr Gynecol 106: 1071–1083.
Gaynes BN, Gavin N, Meltzer-Brody S, Lohr KN, Swinson T, Gartlehner G et al (2005). Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ) 119: 1–8.
Gibson J, McKenzie-McHarg K, Shakespeare J, Price J, Gray R (2009). A systematic review of studies validating the Edinburgh postnatal depression Scale in antepartum and postpartum women. Acta Psychiatrica Scandinavica 119: 350–364.
Gimpl G, Fahrenholz F (2001). The Oxytocin receptor system: Structure, function, and regulation. Physiol Rev 81: 629–683.
Gordon I, Zagoory-Sharon O, Leckman JF, Feldman R (2010). Oxytocin and the development of parenting in humans. Biol Psychiatry 68: 377–382.
Grace SL, Evindar A, Stewart DE (2003). The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health 6: 263–274.
Green AD, Barr AM, Galea LAM (2009). Role of estradiol withdrawal in ‘anhedonic’ sucrose consumption: A model of postpartum depression. Physiol Behav 97: 259–265.
Harris B, Huckle P, Thomas R, Johns S, Fung H (1989). The use of rating-scales to identify post-natal depression. Br J Psychiatry 154: 813–817.
Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003). Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54: 1389–1398.
Heinrichs M, Domes G (2008). Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans. Adv Vasopressin Oxytocin: from Genes to Behav to Disease 170: 337–350.
Hendrick V, Altshuler L, Strouse T, Grosser S (2000). Postpartum and nonpostpartum depression: Differences in presentation and response to pharmacologic treatment. Depress Anxiety 11: 66–72.
Higuchi T, Kaba H (1997). Neuromodulatory role of oxytocin in the control of maternal behavior. In: Maeda K-I, Tsukamura H, Yokoyama A (eds). Neural control of reproduction: Physiology and behavior. S. Karger AG: New York. pp 237–248.
Holman SD, Goy RW (1995). Experiential and hormonal correlates of care-giving in rhesus macaques. In: Pryce CR, Martin RD, Skuse D (eds). Motherhood in Human and Nonhuman Primates. Karger: Basel. pp 87–93.
Insel TR (1997). A neurobiological basis of social attachment. Am J Psychiatry 154: 726–735.
Jardri R, Pelta J, Maron M, Thomas P, Delion P, Codaccioni X et al (2006). Predictive validation study of the Edinburgh postnatal depression scale in the first week after delivery and risk analysis for postnatal depression. J Affect Disord 93: 169–176.
Jones PM, Robinson I, Harris MC (1983). Release of oxytocin into blood and cerebrospinal-fluid by electrical-stimulation of the hypothalamus or neural lobe in the rat. Neuroendocrinology 37: 454–458.
Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M et al (2010). Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology 35: 2403–2413.
Landgraf R, Kubota M, Holsboer F, Wotjak CT (1995). Release of vasopressin and oxytocin within the brain and into blood: Microdialysis and antisense targeting. Neurohypophysis 1098: 243–256.
Landgraf R, Neumann ID (2004). Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrinol 25: 150–176.
Leake RD, Weitzman RE, Glatz TH, Fisher DA (1981). Plasma oxytocin concentrations in men, non-pregnant women, and pregnant-women before and during spontaneous labor. J Clin Endocrinol Metabol 53: 730–733.
Levine A, Zagoory-Sharon O, Feldman R, Weller A (2007). Oxytocin during pregnancy and early postpartum: Individual patterns and maternal-fetal attachment. Peptides 28: 1162–1169.
Light KC, Grewen KM, Amico JA, Boccia M, Brownley KA, Johns JM (2004). Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy. Addict Behav 29: 1541–1564.
Martins C, Gaffan EA (2000). Effects of early maternal depression on patterns of infant-mother attachment: A meta-analytic investigation. J Child Psychol Psychiatry 41: 737–746.
McKenzie DN, Leng G, Dyball REJ (1995). Electrophysiological evidence for mutual excitation of oxytocin cells in the supraoptic nucleus of the rat hypothalamus. J Physiol London 485: 485–492.
Meinlschmidt G, Martin C, Neumann ID, Heinrichs M (2010). Maternal cortisol in late pregnancy and hypothalamic-pituitary-adrenal reactivity to psychosocial stress postpartum in women. Stress-the Int J Biol Stress 13: 163–171.
Murray L, Kempton C, Woolgar M, Hooper R (1993). Depressed Mothers Speech to Their Infants and Its Relation to Infant Gender and Cognitive-Development. J Child Psychol Psychiatry 34: 1083–1101.
Nelson EE, Panksepp J (1998). Brain substrates of infant-mother attachment: Contributions of opioids, oxytocin, and norepinephrine. Neurosci Biobehav Rev 22: 437–452.
Neumann I, Koehler E, Landgraf R, Summylong J (1994). An Oxytocin receptor antagonist infused into the supraoptic nucleus attenuates intranuclear and peripheral release of oxytocin during suckling in conscious rats. Endocrinology 134: 141–148.
O’Hara MW, Swain AM (1996). Rates and risk of postpartum depression—A meta-analysis. Int Rev Psychiatry 8: 37–54.
Olazabal DE, Young LJ (2005). Oxytocin receptors in the nucleus accumbens facilitate ‘spontaneous’ maternal behavior in female prairie voles. Hormones Behav 48: 177.
Ozsoy S, Esel E, Kula M (2009). Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Res 169: 249–252.
Pedersen CA, Vadlamudi SV, Boccia ML, Amico JA (2006). Maternal behavior deficits in nulliparous oxytocin knockout mice. Genes Brain Behav 5: 274–281.
Pop VJM, Derooy HAM, Vader HL, Vanderheide D, Vanson MM, Komproe IH (1993). Microsomal antibodies during gestation in relation to postpartum thyroid-dysfunction and depression. Acta Endocrinologica 129: 26–30.
Robertson E, Grace S, Wallington T, Stewart DE (2004). Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psychiatry 26: 289–295.
Russell JA, Leng G, Douglas AJ (2003). The magnocellular oxytocin system, the fount of maternity: adaptations in pregnancy. Front Neuroendocrinol 24: 27–61.
Sala NL, Althabe O (1968). The milk ejecting effect induced by oxytocin during human lactation. Acta Physiol Lat Am 18: 96–103.
Scantamburlo G, Hansenne M, Fuchs S, Pitchot W, Marechal P, Pequeux C et al (2007). Plasma oxytocin levels and anxiety in patients with major depression. Psychoneuroendocrinology 32: 407–410.
Smith R (1998). Alterations in the hypothalamic pituitary adrenal axis during pregnancy and the placental clock that determines the length of parturition. J Reprod Immunol 39: 215–220.
Stein A, Arteche A, Lehtonen A, Craske M, Harvey A, Counsell N et al (2010). Interpretation of infant facial expression in the context of maternal postnatal depression. Infant Behav Dev 33: 273–278.
Tops M, Van Peer JM, Korf J, Wijers AA, Tucker DM (2007). Anxiety, cortisol, and attachment predict plasma oxytocin. Psychophysiology 44: 444–449.
Uvnas-Moberg K (1998). Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology 23: 819–835.
van der Post JAM, van Buul BJA, Hart AAM, van Heerikhuize JJ, Pesman G, Legros JJ et al (1997). Vasopressin and oxytocin levels during normal pregnancy: Effects of chronic dietary sodium restriction. J Endocrinol 152: 345–354.
van Leengoed E, Kerker E, Swanson HH (1987). Inhibition of postpartum maternal-behavior in the rat by injecting an oxytocin antagonist into the cerebral-ventricles. J Endocrinol 112: 275–282.
Wismer Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD (2005). Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Natl Acad Sci USA 102: 17237–17240.
Wisner KL, Stowe ZN (1997). Psychobiology of postpartum mood disorders. Sem Reprod Endocrinol 15: 77–89.
Wittchen H-U, Lachner G, Wunderlich U, Pfister H (1998). Test-restes reliability of the computerized DSM-IV version of the Munich Composite International Diagnostic Interview (M-CIDI). Soc Psychiatry Psychiatric Epidemiol 33: 568–578.
Wittchen HU, Pfister H (1997). Instruktionsmanual zur Durchführung von DIA-X-Interview). Swets Test Services: Frankfurt.
World Health Organization (1990). Composite International Diagnostic Interview (CIDI): a) CIDI-interview (version 1.0), b) CIDI-user manual, c) CIDI-training manual, d) CIDI-computer programs. World Health Organization: Geneva.
Wotjak CT, Ganster J, Kohl G, Holsboer F, Landgraf R, Engelmann M (1998). Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: New insights into the secretory capacities of peptidergic neurons. Neuroscience 85: 1209–1222.
Yim IS, Glynn LM, Schetter CD, 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: 162–169.
Acknowledgements
This work is part of the National Centre of Competence in Research (NCCR) Swiss Etiological Study of Adjustment and Mental Health (sesam). The Swiss National Science Foundation (SNF) (project no. 51A240-104890), the University of Basel, the Hoffmann-La Roche Corp. and the Basel Scientific Society provided core support for the NCCR sesam. We are grateful to the Max Planck Institute of Psychiatry, Munich, Germany for the biochemical analyses. Further, we thank Andrea H Meyer, PhD, for his statistical support.
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Skrundz, M., Bolten, M., Nast, I. et al. Plasma Oxytocin Concentration during Pregnancy is associated with Development of Postpartum Depression. Neuropsychopharmacol 36, 1886–1893 (2011). https://doi.org/10.1038/npp.2011.74
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DOI: https://doi.org/10.1038/npp.2011.74
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