Prenatal Major Depressive Disorder, Placenta Glucocorticoid and Serotonergic Signaling, and Infant Cortisol Response

Overview

Journal Psychosom Med

Specialty Psychiatry

Date 2016 Nov 5

PMID 27763986

Citations 34

Authors

Laura R Stroud

George D Papandonatos

Stephanie H Parade

Amy L Salisbury

Maureen G Phipps

Barry M Lester

James F Padbury

Carmen J Marsit

Affiliations

Soon will be listed here.

Abstract

Objectives: Extending prior studies of prenatal adversity and depressive symptoms, we tested associations between maternal prenatal major depressive disorder (MDD) and infant cortisol regulation. Based on prior findings by our group, we also tested placenta glucocorticoid (HSD11B2 methylation) and serotonin (SLC6A4 gene expression) signaling as moderators of links between prenatal MDD and infant cortisol.

Methods: Participants were 153 mother-infant pairs from a low-income, diverse sample (M [SD] age = 26 [6] years). Repeated structured diagnostic interviews were used to identify mothers with (a) prenatal MDD, (b) preconception-only MDD, and (c) controls. Placenta samples were assayed for HSD11B2 methylation and SLC6A4 gene expression. Infant salivary cortisol response to a neurobehavioral examination was assessed at 1 month.

Results: Daughters of prenatal MDD mothers had 51% higher baseline (ratio = 1.51; 95% confidence interval [CI] = 1.01-2.27; p = .045) and 64% higher stress responsive cortisol (ratio = 1.64; 95% CI = 1.05-2.56; p = .03) than daughters of controls and 75% higher stress-responsive cortisol (ratio = 1.75; 95% CI = 1.04-2.94; p = .04) than daughters of preconception-only MDD mothers. HSD11B2 methylation moderated links between prenatal MDD and baseline cortisol (p = .02), with 1% methylation decreases associated with 9% increased baseline cortisol in infants of prenatal MDD mothers (ratio = 1.09; 95% CI = 1.01-1.16). SLC6A4 expression moderated links between prenatal MDD and cortisol response among boys alone (p = .007), with 10-fold increases in expression associated with threefold increases in stress-responsive cortisol (ratio = 2.87; 95% CI = 1.39-5.93) in sons of control mothers.

Conclusions: Results highlight specificity of associations between prenatal versus preconception MDD and cortisol regulation and the importance and complexity of placenta glucocorticoid and serotonergic pathways underlying the intergenerational transmission of risk from maternal adversity.

Citing Articles

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References

Jones N, Field T, Fox N, Lundy B, Davalos M . EEG activation in 1-month-old infants of depressed mothers. Dev Psychopathol. 1997; 9(3):491-505. DOI: 10.1017/s0954579497001260. View

Davis E, Glynn L, Dunkel Schetter C, Hobel C, Chicz-DeMet A, Sandman C . Prenatal exposure to maternal depression and cortisol influences infant temperament. J Am Acad Child Adolesc Psychiatry. 2007; 46(6):737-746. DOI: 10.1097/chi.0b013e318047b775. View

ODonnell K, Glover V, Jenkins J, Browne D, Ben-Shlomo Y, Golding J . Prenatal maternal mood is associated with altered diurnal cortisol in adolescence. Psychoneuroendocrinology. 2013; 38(9):1630-8. PMC: 3695029. DOI: 10.1016/j.psyneuen.2013.01.008. View

Monk C, Sloan R, Myers M, Ellman L, Werner E, Jeon J . Fetal heart rate reactivity differs by women's psychiatric status: an early marker for developmental risk?. J Am Acad Child Adolesc Psychiatry. 2004; 43(3):283-90. DOI: 10.1097/00004583-200403000-00009. View

Rifkin-Graboi A, Bai J, Chen H, Hameed W, Sim L, Thway Tint M . Prenatal maternal depression associates with microstructure of right amygdala in neonates at birth. Biol Psychiatry. 2013; 74(11):837-44. DOI: 10.1016/j.biopsych.2013.06.019. View

Pfaffl M . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29(9):e45. PMC: 55695. DOI: 10.1093/nar/29.9.e45. View

Sandman C, Glynn L, Davis E . Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res. 2013; 75(4):327-35. PMC: 3796732. DOI: 10.1016/j.jpsychores.2013.07.009. View

Laurent H, Ablow J, Measelle J . Risky shifts: how the timing and course of mothers' depressive symptoms across the perinatal period shape their own and infant's stress response profiles. Dev Psychopathol. 2013; 23(2):521-38. DOI: 10.1017/S0954579411000083. View

Moore C, Lewis D, Becker J, Leikin J . The determination of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in meconium. J Anal Toxicol. 1996; 20(1):50-1. DOI: 10.1093/jat/20.1.50. View

10.

Oberlander T, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin A . Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3(2):97-106. DOI: 10.4161/epi.3.2.6034. View

11.

Jans L, Riedel W, Markus C, Blokland A . Serotonergic vulnerability and depression: assumptions, experimental evidence and implications. Mol Psychiatry. 2006; 12(6):522-43. DOI: 10.1038/sj.mp.4001920. View

12.

Maccani M, Marsit C . Epigenetics in the placenta. Am J Reprod Immunol. 2009; 62(2):78-89. PMC: 2813777. DOI: 10.1111/j.1600-0897.2009.00716.x. View

13.

Egliston K, McMahon C, Austin M . Stress in pregnancy and infant HPA axis function: conceptual and methodological issues relating to the use of salivary cortisol as an outcome measure. Psychoneuroendocrinology. 2006; 32(1):1-13. DOI: 10.1016/j.psyneuen.2006.10.003. View

14.

Salisbury A, OGrady K, Battle C, Wisner K, Anderson G, Stroud L . The Roles of Maternal Depression, Serotonin Reuptake Inhibitor Treatment, and Concomitant Benzodiazepine Use on Infant Neurobehavioral Functioning Over the First Postnatal Month. Am J Psychiatry. 2015; 173(2):147-57. PMC: 4742381. DOI: 10.1176/appi.ajp.2015.14080989. View

15.

Le Strat Y, Dubertret C, Le Foll B . Prevalence and correlates of major depressive episode in pregnant and postpartum women in the United States. J Affect Disord. 2011; 135(1-3):128-38. DOI: 10.1016/j.jad.2011.07.004. View

16.

Gentile S . Untreated depression during pregnancy: Short- and long-term effects in offspring. A systematic review. Neuroscience. 2015; 342:154-166. DOI: 10.1016/j.neuroscience.2015.09.001. View

17.

Rush A, Gullion C, Basco M, Jarrett R, Trivedi M . The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med. 1996; 26(3):477-86. DOI: 10.1017/s0033291700035558. View

18.

Sandman C, Davis E, Buss C, Glynn L . Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus. Neuroendocrinology. 2011; 95(1):7-21. PMC: 7068789. DOI: 10.1159/000327017. View

19.

Muller M . A questionnaire to measure mother-to-infant attachment. J Nurs Meas. 1994; 2(2):129-41. View

20.

Pruessner J, Kirschbaum C, Meinlschmid G, Hellhammer D . Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology. 2003; 28(7):916-31. DOI: 10.1016/s0306-4530(02)00108-7. View