Hostname: page-component-6bf8c574d5-pdxrj Total loading time: 0 Render date: 2025-03-10T16:20:54.652Z Has data issue: false hasContentIssue false
  • English
  • Français

Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways

Published online by Cambridge University Press:  15 October 2012

Catherine Monk ,
Julie Spicer  and
Frances A. Champagne
Catherine Monk
Affiliation:
Columbia University
Julie Spicer
Affiliation:
Columbia University
Frances A. Champagne*
Affiliation:
Columbia University
*
Address correspondence and reprint requests to: Frances A. Champagne, Department of Psychology, Columbia University, 1190 Amsterdam Avenue, Room 406, Schermerhorn Hall, New York, NY 10027; E-mail: fac2105@columbia.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with risk of psychopathology. Although the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this article, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and we review findings illustrating prenatal–postnatal interplay and the developmental and epigenetic consequences of postnatal mother–infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress.

Type
Articles
Information
Development and Psychopathology , Volume 24 , Issue 4: Contributions of the Genetic/Genomic Sciences to Developmental Psychopathology , November 2012 , pp. 1361 - 1376
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Angiolini, E., Fowden, A., Coan, P., Sandovici, I., Smith, P., Dean, W., et al. (2006). Regulation of placental efficiency for nutrient transport by imprinted genes. Placenta, 27(Suppl. A), S98–S102.CrossRefGoogle ScholarPubMed
Bagner, D. M., Pettit, J. W., Lewinsohn, P. M., & Seeley, J. R. (2010). Effect of maternal depression on child behavior: A sensitive period? Journal of the American Academy of Child & Adolescent Psychiatry, 49, 699–707.Google ScholarPubMed
Bale, T. L., Baram, T. Z., Brown, A. S., Goldstein, J. M., Insel, T. R., McCarthy, M. M., et al. (2010). Early life programming and neurodevelopmental disorders. Biological Psychiatry, 68, 314–319.CrossRefGoogle ScholarPubMed
Barski, A., Cuddapah, S., Cui, K., Roh, T. Y., Schones, D. E., Wang, Z., et al. (2007). High-resolution profiling of histone methylations in the human genome. Cell, 129, 823–837.CrossRefGoogle ScholarPubMed
Beck, C. T. (1996). A meta-analysis of predictors of postpartum depression. Nursing Research, 45, 297–303.CrossRefGoogle ScholarPubMed
Beebe, B., Badalamenti, A., Jaffe, J., Feldstein, S., Marquette, L., Helbraun, E., et al. (2008). Distressed mothers and their infants use a less efficient timing mechanism in creating expectancies of each other's looking patterns. Journal of Psycholinguist Research, 37, 293–307.CrossRefGoogle ScholarPubMed
Beebe, B., Steele, M., Jaffe, J., Buck, K., Chen, H., Cohen, P., et al. (2011). Maternal anxiety symptoms and mother–infant self- and interactive contingency. Infant Mental Health Journal, 32, 174–206.CrossRefGoogle ScholarPubMed
Bergman, K., Sarkar, P., Glover, V., & O'Connor, T. G. (2010). Maternal prenatal cortisol and infant cognitive development: Moderation by infant–mother attachment. Biological Psychiatry, 67, 1026–1032.CrossRefGoogle ScholarPubMed
Bergman, K., Sarkar, P., O'Connor, T. G., Modi, N., & Glover, V. (2007). Maternal stress during pregnancy predicts cognitive ability and fearfulness in infancy. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 1454–1463.CrossRefGoogle ScholarPubMed
Bettes, B. A. (1989). Maternal depression and motherese: Temporal and intonational features. Child Development, 59, 1089–1096.CrossRefGoogle Scholar
Beversdorf, D. Q., Manning, S. E., Hillier, A., Anderson, S. L., Nordgren, R. E., Walters, S. E., et al. (2005). Timing of prenatal stressors and autism. Journal of Autism & Devopmental Disorders, 35, 471–478.CrossRefGoogle ScholarPubMed
Beydoun, H., & Saftlas, A. F. (2008). Physical and mental health outcomes of prenatal maternal stress in human and animal studies: A review of recent evidence. Paediatric & Perinatal Epidemiology, 22, 438–466.CrossRefGoogle ScholarPubMed
Blair, M. M., Glynn, L. M., Sandman, C. A., & Davis, E. P. (2011). Prenatal maternal anxiety and early childhood temperament. Stress, 14, 644–651.CrossRefGoogle ScholarPubMed
Borzsonyi, B., Demendi, C., Pajor, A., Rigo, J. Jr., Marosi, K., Agota, A., et al. (2012). Gene expression patterns of the 11beta-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: The role of impaired feto-maternal glucocorticoid metabolism. European Journal of Obstetrics and Gynecology and Reproductive Biology, 161, 12–17.CrossRefGoogle ScholarPubMed
Brown, A. S., Van Os, J., Driessens, C., Hoek, H. W., & Susser, E. S. (2000). Further evidence of relation between prenatal famine and major affective disorder. American Journal of Psychiatry, 157, 190–195.CrossRefGoogle ScholarPubMed
Bureau, J. F., Easterbrooks, M. A., & Lyons-Ruth, K. (2009). Maternal depressive symptoms in infancy: Unique contribution to children's depressive symptoms in childhood and adolescence? Development and Psychopathology, 21, 519–537.CrossRefGoogle ScholarPubMed
Buss, C., Davis, E. P., Muftuler, L. T., Head, K., & Sandman, C. A. (2010). High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6–9-year-old children. Psychoneuroendocrinology, 35, 141–153.CrossRefGoogle ScholarPubMed
Bystrova, K., Ivanova, V., Edhborg, M., Matthiesen, A. S., Ransjo-Arvidson, A. B., Mukhamedrakhimov, R., et al. (2009). Early contact versus separation: Effects on mother–infant interaction one year later. Birth, 36, 97–109.CrossRefGoogle ScholarPubMed
Caldji, C., Tannenbaum, B., Sharma, S., Francis, D., Plotsky, P. M., & Meaney, M. J. (1998). Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proceedings of the National Academy of Sciences, 95, 5335–5340.CrossRefGoogle ScholarPubMed
Cameron, N., Del Corpo, A., Diorio, J., McAllister, K., Sharma, S., & Meaney, M. J. (2008a). Maternal programming of sexual behavior and hypothalamic–pituitary–gonadal function in the female rat. PLoS ONE, 3, e2210.CrossRefGoogle ScholarPubMed
Cameron, N. M., Fish, E. W., & Meaney, M. J. (2008b). Maternal influences on the sexual behavior and reproductive success of the female rat. Hormones & Behavior, 54, 178–184.CrossRefGoogle ScholarPubMed
Champagne, D. L., Bagot, R. C., van Hasselt, F., Ramakers, G., Meaney, M. J., de Kloet, E. R., et al. (2008). Maternal care and hippocampal plasticity: Evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. Journal of Neuroscience, 28, 6037–6045.CrossRefGoogle ScholarPubMed
Champagne, F., Diorio, J., Sharma, S., & Meaney, M. J. (2001). Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proceedings of the National Academy of Sciences, 98, 12736–12741.CrossRefGoogle ScholarPubMed
Champagne, F. A. (2008). Epigenetic mechanisms and the transgenerational effects of maternal care. Frontiers in Neuroendocrinology, 29, 386–397.CrossRefGoogle ScholarPubMed
Champagne, F. A. (2010). Epigenetic influence of social experiences across the lifespan. Developmental Psychobiology, 52, 299–311.CrossRefGoogle ScholarPubMed
Champagne, F. A., Francis, D. D., Mar, A., & Meaney, M. J. (2003). Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiology & Behavior, 79, 359–371.CrossRefGoogle ScholarPubMed
Champagne, F. A., & Meaney, M. J. (2006). Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biological Psychiatry, 59, 1227–1235.CrossRefGoogle Scholar
Champagne, F. A., & Meaney, M. J. (2007). Transgenerational effects of social environment on variations in maternal care and behavioral response to novelty. Behavioral Neuroscience, 121, 1353–1363.CrossRefGoogle ScholarPubMed
Champagne, F. A., Weaver, I. C., Diorio, J., Dymov, S., Szyf, M., & Meaney, M. J. (2006). 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, 147, 2909–2915.CrossRefGoogle ScholarPubMed
Champagne, F. A., Weaver, I. C., Diorio, J., Sharma, S., & Meaney, M. J. (2003). Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area. Endocrinology, 144, 4720–4724.CrossRefGoogle ScholarPubMed
Charil, A., Laplante, D. P., Vaillancourt, C., & King, S. (2010). Prenatal stress and brain development. Brain Research Reviews, 65, 56–79.CrossRefGoogle ScholarPubMed
Clarke, A. S., & Schneider, M. L. (1997). Effects of prenatal stress on behavior in adolescent rhesus monkeys. Annals of the New York Academy of Sciences, 807, 490–491.CrossRefGoogle ScholarPubMed
Cohn, J. F., Matias, R., Tronick, E. Z., Connell, D., & Lyons-Ruth, K. (1986). Face-to-face interactions of depressed mothers and their infants. New Directions for Child Development, 34, 31–45.CrossRefGoogle Scholar
Cottrell, E. C., & Seckl, J. R. (2009). Prenatal stress, glucocorticoids and the programming of adult disease. Frontiers in Behavioral Neuroscience, 3, 19.CrossRefGoogle ScholarPubMed
Crnic, K. A., Greenberg, M. T., Robinson, N. M., & Ragozin, A. S. (1984). Maternal stress and social support: Effects on the infant–mother relationship from birth to eighteen months. American Journal of Orthopsychiatry, 54, 224–235.CrossRefGoogle Scholar
Davis, E. P., Glynn, L. M., Schetter, C. D., Hobel, C., Chicz-Demet, A., & Sandman, C. A. (2007). Prenatal exposure to maternal depression and cortisol influences infant temperament. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 737–746.CrossRefGoogle ScholarPubMed
Davis, E. P., Glynn, L. M., Waffarn, F., & Sandman, C. A. (2011). Prenatal maternal stress programs infant stress regulation. Journal of Child Psychology and Psychiatry, 52, 119–129.CrossRefGoogle ScholarPubMed
Davis, P. E., Snidman, N., Wadhwa, P., Glynn, L. M., Schetter, C. D., & Sandman, C. A. (2004). Prenatal maternal anxiety and depression predict negative behavioral reactivity in infancy. Infancy, 6, 319–331.CrossRefGoogle Scholar
Dawson, G., Klinger, L. G., Panagiotides, H., Hill, D., & Spieker, S. (1992). Frontal lobe activity and affective behavior of infants of mothers with depressive symptoms. Child Development, 63, 725–737.CrossRefGoogle ScholarPubMed
Desforges, M., & Sibley, C. P. (2010). Placental nutrient supply and fetal growth. International Journal of Developmental Biology, 54 (2–3), 377–390.CrossRefGoogle ScholarPubMed
Devlin, A. M., Brain, U., Austin, J., & Oberlander, T. F. (2010). Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS ONE, 5, e12201.CrossRefGoogle ScholarPubMed
Dieter, J. N. I., Field, T., Hernandez-Reif, M., Jones, N. A., Lecanuet, J. P., Salman, F. A., et al. (2001). Maternal depression and increased fetal activity. Journal of Obstetrics and Gynaecology, 21, 468–473.Google ScholarPubMed
DiPietro, J. A., Bornstein, M. H., Costigan, K. A., Pressman, E. K., Hahn, C. S., Painter, K., et al. (2002). What does fetal movement predict about behavior during the first two years of life? Developmental Psychobiology, 40, 358–371.CrossRefGoogle ScholarPubMed
DiPietro, J. A., Hodgson, D. M., Costigan, K. A., & Johnson, T. R. B. (1996a). Fetal antecedents of infant temperament. Child Development 67, 2568–2583.CrossRefGoogle ScholarPubMed
DiPietro, J. A., Hodgson, K. A., Costigan, S. C., & Johnson, T. R. B. (1996b). Developmental of fetal movement–fetal heart rate coupling from 20 weeks through term. Early Human Development, 44, 139–151.CrossRefGoogle Scholar
DiPietro, J. A., Kivlighan, K. T., Costigan, K. A., & Laudenslager, M. L. (2009). Fetal motor activity and maternal cortisol. Devopmental Psychobiology, 51, 505–512.CrossRefGoogle ScholarPubMed
Dy, J., Guan, H., Sampath-Kumar, R., Richardson, B. S., & Yang, K. (2008). Placental 11beta-hydroxysteroid dehydrogenase type 2 is reduced in pregnancies complicated with idiopathic intrauterine growth restriction: Evidence that this is associated with an attenuated ratio of cortisone to cortisol in the umbilical artery. Placenta, 29, 193–200.CrossRefGoogle ScholarPubMed
Emory, E. K., & Dieter, J. N. (2006). Maternal depression and psychotropic medication effects on the human fetus. Annals of the New York Academy of Sciences, 1094, 287–291.CrossRefGoogle ScholarPubMed
Fan, G., & Hutnick, L. (2005). Methyl-CpG binding proteins in the nervous system. Cell Research, 15, 255–261.CrossRefGoogle ScholarPubMed
Feldman, R., Granat, A., Pariente, C., Kanety, H., Kuint, J., & Gilboa-Schechtman, E. (2009). Maternal depression and anxiety across the postpartum year and infant social engagement, fear regulation, and stress reactivity. Journal of the American Academy of Child & Adolescent Psychiatry, 48, 919–927.CrossRefGoogle ScholarPubMed
Field, T. (1998). Maternal depression effects on infants and early interventions. Preventive Medicine, 27, 200–203.CrossRefGoogle ScholarPubMed
Field, T. (2002). Early interactions between infants and their postpartum depressed mothers. Infant Behavior and Development, 25, 25–29.CrossRefGoogle Scholar
Field, T. (2010). Touch for socioemotional and physical well-being: A review. Developmental Review, 30, 367–383.CrossRefGoogle Scholar
Forman, D. R., O'Hara, M. W., Stuart, S., Gorman, L. L., Larsen, K. E., & Coy, K. C. (2007). Effective treatment for postpartum depression is not sufficient to improve the developing mother–child relationship. Development and Psychopathology, 19, 585–602.CrossRefGoogle Scholar
Gianino, A., & Tronick, E. (1985). The mutual regulation model: The infant's self and interactive regulation and coping and defensive capacities. In T. Field, P. McCabe, & N. Schneiderman (Eds.), Stress and coping (pp. 47–68). Hillsdale, NJ: Erlbaum.Google Scholar
Glynn, L. M., Wadhwa, P. D., Dunkel-Schetter, C., Chicz-Demet, A., & Sandman, C. A. (2001). When stress happens matters: Effects of earthquake timing on stress responsivity in pregnancy. American Journal of Obstetrics & Gynecology, 184, 637–642.CrossRefGoogle ScholarPubMed
Goodman, S. H., & Gotlib, I. H. (1999). Risk for psychopathology in the children of depressed mothers: A developmental model for understanding mechanisms of transmission. Psychological Review, 106, 458–490.CrossRefGoogle ScholarPubMed
Gotlib, I. H., Whiffen, V. E., Mount, J. H., Milne, K., & Cordy, N. I. (1989). Prevalence rates and demographic characteristics associated with depression in pregnancy and the postpartum. Journal of Consulting and Clinical Psychology, 57, 269–274.CrossRefGoogle ScholarPubMed
Goyal, D., Gay, C., & Lee, K. A. (2010). How much does low socioeconomic status increase the risk of prenatal and postpartum depressive symptoms in first-time mothers? Womens Health Issues, 20, 96–104.CrossRefGoogle ScholarPubMed
Grant, K. A., McMahon, C., Austin, M. P., Reilly, N., Leader, L., & Ali, S. (2009). Maternal prenatal anxiety, postnatal caregiving and infants' cortisol responses to the still-face procedure. Developmental Psychobiology, 51, 625–637.CrossRefGoogle Scholar
Groome, L. J., Swiber, M. J., Bentz, L. S., Holland, S. B., & Atterbury, J. L. (1995). Maternal anxiety during pregnancy: Effect on fetal behavior at 38 to 40 weeks of gestation. Developmental and Behavioral Pediatrics, 16, 391–396.CrossRefGoogle ScholarPubMed
Hane, A. A., & Fox, N. A. (2006). Ordinary variations in maternal caregiving influence human infants' stress reactivity. Psychological Science, 17, 550–556.CrossRefGoogle ScholarPubMed
Hane, A. A., Henderson, H. A., Reeb-Sutherland, B. C., & Fox, N. A. (2010). Ordinary variations in human maternal caregiving in infancy and biobehavioral development in early childhood: A follow-up study. Developmental Psychobiology, 52, 558–567.CrossRefGoogle ScholarPubMed
Heijmans, B. T., Tobi, E. W., Stein, A. D., Putter, H., Blauw, G. J., Susser, E. S., et al. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings of the National Academy of Sciences, 105, 17046–17049.CrossRefGoogle ScholarPubMed
Hoek, H. W., Brown, A. S., & Susser, E. (1998). The Dutch famine and schizophrenia spectrum disorders. Social Psychiatry and Psychiatric Epidemiology, 33, 373–379.CrossRefGoogle ScholarPubMed
Jablonka, E., & Lamb, M. J. (2002). The changing concept of epigenetics. Annals of the New York Academy of Sciences, 981, 82–96.CrossRefGoogle ScholarPubMed
Jenuwein, T., & Allis, C. D. (2001). Translating the histone code. Science, 293(5532), 1074–1080.CrossRefGoogle ScholarPubMed
Jirtle, R. L., & Skinner, M. K. (2007). Environmental epigenomics and disease susceptibility. Nature Reviews in Genetics, 8, 253–262.CrossRefGoogle ScholarPubMed
Jones, P. A., & Taylor, S. M. (1980). Cellular differentiation, cytidine analogs and DNA methylation. Cell, 20, 85–93.CrossRefGoogle ScholarPubMed
Kaitz, M., Maytal, H. R., Devor, N., Bergman, L., & Mankuta, D. (2010). Maternal anxiety, mother–infant interactions, and infants' response to challenge. Infant Behavior & Development, 33, 136–148.CrossRefGoogle ScholarPubMed
Kaplan, L. A., Evans, L., & Monk, C. (2007). Effects of mothers' prenatal psychiatric status and postnatal caregiving on infant biobehavioral regulation: Can prenatal programming be modified? Early Human Development, 84, 249–256.CrossRefGoogle ScholarPubMed
Khashan, A. S., Abel, K. M., McNamee, R., Pedersen, M. G., Webb, R. T., Baker, P. N., et al. (2008). Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Archives of General Psychiatry, 65, 146–152.CrossRefGoogle ScholarPubMed
Kikkert, H. K., Middelburg, K. J., & Hadders-Algra, M. (2010). Maternal anxiety is related to infant neurological condition, paternal anxiety is not. Early Human Development, 86, 171–177.CrossRefGoogle ScholarPubMed
King, S., & Laplante, D. P. (2005). The effects of prenatal maternal stress on children's cognitive development: Project Ice Storm. Stress, 8, 35–45.CrossRefGoogle ScholarPubMed
Kinnally, E. L., Capitanio, J. P., Leibel, R., Deng, L., LeDuc, C., Haghighi, F., et al. (2010). Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes, Brain, and Behavior, 9, 575–582.CrossRefGoogle ScholarPubMed
Kinney, D. K., Miller, A. M., Crowley, D. J., Huang, E., & Gerber, E. (2008). Autism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana. Journal of Autism & Developmental Disorders, 38, 481–488.CrossRefGoogle ScholarPubMed
Kleefstra, T., Brunner, H. G., Amiel, J., Oudakker, A. R., Nillesen, W. M., Magee, A., et al. (2006). Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome. American Journal of Human Genetics, 79, 370–377.CrossRefGoogle ScholarPubMed
Koch, C. M., Andrews, R. M., Flicek, P., Dillon, S. C., Karaoz, U., Clelland, G. K., et al. (2007). The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Research, 17, 691–707.CrossRefGoogle ScholarPubMed
Kurian, J. R., Olesen, K. M., & Auger, A. P. (2010). Sex differences in epigenetic regulation of the estrogen receptor-alpha promoter within the developing preoptic area. Endocrinology, 151, 2297–2305.CrossRefGoogle ScholarPubMed
Lambertini, L., Lee, T. L., Chan, W. Y., Lee, M. J., Diplas, A., Wetmur, J., et al. (2011). Differential methylation of imprinted genes in growth-restricted placentas. Reproductive Sciences, 18, 1111–1117.CrossRefGoogle ScholarPubMed
Laplante, D. P., Barr, R. G., Brunet, A., Galbaud du Fort, G., Meaney, M. L., Saucier, J. F., et al. (2004). Stress during pregnancy affects general intellectual and language functioning in human toddlers. Pediatric Research, 56, 400–410.CrossRefGoogle ScholarPubMed
Laplante, D. P., Brunet, A., Schmitz, N., Ciampi, A. & King, S. (2008). Project Ice Storm: Prenatal maternal stress affects cognitive and linguistic functioning in 5½-year-old children. Journal of the American Academy of Child & Adolescent Psychiatry, 47, 1063–1072.CrossRefGoogle Scholar
Lee, M. H., Jeon, Y. J., Lee, S. M., Park, M. H., Jung, S. C., & Kim, Y. J. (2010). Placental gene expression is related to glucose metabolism and fetal cord blood levels of insulin and insulin-like growth factors in intrauterine growth restriction. Early Human Development, 86, 45–50.CrossRefGoogle ScholarPubMed
Legube, G., & Trouche, D. (2003). Regulating histone acetyltransferases and deacetylases. EMBO Reports, 4, 944–947.CrossRefGoogle ScholarPubMed
Lehmann, J., Pryce, C. R., Jongen-Relo, A. L., Stohr, T., Pothuizen, H. H., & Feldon, J. (2002). Comparison of maternal separation and early handling in terms of their neurobehavioral effects in aged rats. Neurobiology of Aging, 23, 457–466.CrossRefGoogle ScholarPubMed
Levy, G. (1981). Pharmacokinetics of fetal and neonatal exposure to drugs. Obstetrics and Gynecology, 58(Suppl. 5), 9S–16S.Google ScholarPubMed
Li, E., Bestor, T. H., & Jaenisch, R. (1992). Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell, 69, 915–926.CrossRefGoogle ScholarPubMed
Li, J., Vestergaard, M., Obel, C., Christensen, J., Precht, D. H., Lu, M., et al. (2009). A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement. Pediatrics, 123, 1102–1107.CrossRefGoogle Scholar
Liu, D., Diorio, J., Day, J. C., Francis, D. D., & Meaney, M. J. (2000). Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nature Neuroscience, 3, 799–806.CrossRefGoogle ScholarPubMed
Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., et al. (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress. Science, 277(5332), 1659–1662.CrossRefGoogle ScholarPubMed
Lupien, S. J., Parent, S., Evans, A. C., Tremblay, R. E., Zelazo, P. D., Corbo, V., et al. (2011). Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proceedings of the National Academy of Sciences, 108, 14324–14329.CrossRefGoogle ScholarPubMed
Lyons-Ruth, K., & Block, D. (1996). The disturbed caregiving system: Relations among childhood trauma, maternal caregiving, and infant affect and attachment. Infant Mental Health Journal, 17, 257–275.3.0.CO;2-L>CrossRefGoogle Scholar
Mairesse, J., Lesage, J., Breton, C., Breant, B., Hahn, T., Darnaudery, M., et al. (2007). Maternal stress alters endocrine function of the feto-placental unit in rats. American Journal of Physiology, Endocrinology, and Metabolism, 292, E1526–E1533.CrossRefGoogle ScholarPubMed
Malaspina, D., Corcoran, C., Kleinhaus, K. R., Perrin, M. C., Fennig, S., Nahon, D., et al. (2008). Acute maternal stress in pregnancy and schizophrenia in offspring: A cohort prospective study. BMC Psychiatry, 8, 71.CrossRefGoogle ScholarPubMed
Manian, N., & Bornstein, M. H. (2009). Dynamics of emotion regulation in infants of clinically depressed and nondepressed mothers. Journal of Child Psychology and Psychiatry 50, 1410–1418.CrossRefGoogle ScholarPubMed
Mann, P. E., & Bridges, R. S. (2001). Lactogenic hormone regulation of maternal behavior. Progress in Brain Research, 133, 251–262.CrossRefGoogle ScholarPubMed
Martins, C., & Gaffan, E. A. (2000). Effects of early maternal depression on patterns of infant–mother attachment: A meta-analytic investigation. Journal of Child Psychology and Psychiatry, 41, 737–746.CrossRefGoogle ScholarPubMed
McCarthy, C., Cotter, F. E., McElwaine, S., Twomey, A., Mooney, E. E., Ryan, F., et al. (2007). Altered gene expression patterns in intrauterine growth restriction: potential role of hypoxia. American Journal of Obstetrics and Gynecology, 196, 70e1–e6.CrossRefGoogle ScholarPubMed
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342–348.CrossRefGoogle ScholarPubMed
McMahon, C. A., Barnett, B., Kowalenko, N. M., & Tennant, C. C. (2006). Maternal attachment state of mind moderates the impact of postnatal depression on infant attachment. Journal of Child Psychology and Psychiatry, 47, 660–669.CrossRefGoogle ScholarPubMed
McMinn, J., Wei, M., Schupf, N., Cusmai, J., Johnson, E. B., Smith, A. C., et al. (2006). Unbalanced placental expression of imprinted genes in human intrauterine growth restriction. Placenta, 27, 540–549.CrossRefGoogle ScholarPubMed
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Reviews in Neuroscience, 24, 1161–1192.CrossRefGoogle Scholar
Meaney, M. J., & Szyf, M. (2005). Maternal care as a model for experience-dependent chromatin plasticity? Trends in Neuroscience, 28, 456–463.CrossRefGoogle Scholar
Monk, C., Fifer, W. P., Myers, M. M., Bagiella, E., Duong, J. K., Chen, I. S., et al. (2011). Effects of maternal breathing rate, psychiatric status, and cortisol on fetal heart rate. Developmental Psychobiology, 53, 221–233.CrossRefGoogle ScholarPubMed
Monk, C., Fifer, W. P., Sloan, R. P., Myers, M. M., Trien, L., & Hurtado, A. (2000). Maternal stress responses and anxiety during pregnancy: Effects on fetal heart rate. Developmental Psychobiology, 36, 67–77.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Monk, C., Myers, M. M., Sloan, R. P., Werner, L., Jeon, J., Tager, F., et al. (2004). Fetal heart rate reactivity differs by women's psychiatric status: An early marker for developmental risk? Journal of the American Academy of Child & Adolescent Psychiatry, 43, 283–290.CrossRefGoogle ScholarPubMed
Moore, C. L. (1984). Maternal contributions to the development of masculine sexual behavior in laboratory rats. Developmental Psychobiology, 17, 347–356.CrossRefGoogle Scholar
Moore, C. L., & Morelli, G. A. (1979). Mother rats interact differently with male and female offspring. Journal of Comparative Physiological Psychology, 93, 677–684.CrossRefGoogle ScholarPubMed
Mueller, B. R., & Bale, T. L. (2008). Sex-specific programming of offspring emotionality after stress early in pregnancy. Journal of Neuroscience, 28, 9055–9065.CrossRefGoogle ScholarPubMed
Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmuhl, Y., Fischer, D., et al. (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience, 12, 1559–1566.CrossRefGoogle ScholarPubMed
Murray, L., Halligan, S. L., Goodyer, I., & Herbert, J. (2010). Disturbances in early parenting of depressed mothers and cortisol secretion in offspring: A preliminary study. Journal of Affective Disorders, 122, 218–223.CrossRefGoogle ScholarPubMed
Naumova, O. Y., Lee, M., Koposov, R., Szyf, M., Dozier, M., & Grigorenko, E. L. (2012). Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Development and Psychopathology, 24, 143–155.CrossRefGoogle ScholarPubMed
Nelissen, E. C., van Montfoort, A. P., Dumoulin, J. C., & Evers, J. L. (2011). Epigenetics and the placenta. Human Reproduction Update, 17, 397–417.CrossRefGoogle ScholarPubMed
Nicol-Harper, R., Harvey, A. G., & Stein, A. (2007). Interactions between mothers and infants: Impact of maternal anxiety. Infant Behavior and Development, 30, 161–167.CrossRefGoogle ScholarPubMed
Novakovic, B., Wong, N. C., Sibson, M., Ng, H. K., Morley, R., Manuelpillai, U., et al. (2010). DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta. Journal of Biological Chemistry, 285, 9583–9593.CrossRefGoogle Scholar
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3, 97–106.CrossRefGoogle ScholarPubMed
O'Connor, T. G., Ben-Shlomo, Y., Heron, J., Golding, J., Adams, D., & Glover, V. (2005). Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children. Biological Psychiatry, 58, 211–217.CrossRefGoogle ScholarPubMed
O'Connor, T. G., Heron, J., Glover, V., & the ALSPAC Study Team. (2002). Antenatal anxiety predicts child behavior/emotional problems independently of postnatal depression. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 1470–1477.CrossRefGoogle ScholarPubMed
O'Connor, T. G., Heron, J., Golding, J., Beveridge, M., & Glover, V. (2002). Maternal antenatal anxiety and children's behavioral/emotional problems at 4 years: Report from the Avon Longitudinal Study of Parents and Children. British Journal of Psychiatry, 180, 502–508.CrossRefGoogle Scholar
O'Connor, T. G., Heron, J., Golding, J., & Glover, V. (2003). Maternal antenatal anxiety and behavioural/emotional problems in children: A test of a programming hypothesis. Journal of Child Psychology and Psychiatry, 44, 1025–1036.CrossRefGoogle ScholarPubMed
O'Donnell, K. J., Bugge Jensen, A., Freeman, L., Khalife, N., O'Connor, T. G., & Glover, V. (2011). Maternal prenatal anxiety and downregulation of placental 11beta-HSD2. Psychoneuroendocrinology, 109, E1312–E1319.Google Scholar
O'Hara, M. W., & Swain, A. M. (1996). Rates and risk of postpartum depression: A meta-analysis. International Review of Psychiatry, 8, 37–54.CrossRefGoogle Scholar
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99, 247–257.CrossRefGoogle Scholar
Pawlby, S., Hay, D. F., Sharp, D., Waters, C. S., & O'Keane, V. (2009). Antenatal depression predicts depression in adolescent offspring: Prospective longitudinal community-based study. Journal of Affective Disorders, 113, 236–243.CrossRefGoogle ScholarPubMed
Pesonen, A. K., Raikkonen, K., Strandberg, T. E., & Jarvenpaa, A.-L. (2005). Continuity of maternal stress from the pre- to the postnatal period: Associations with infant's positive, negative, and overall temperamental reactivity. Infant Behavior and Development, 28, 36–47.CrossRefGoogle Scholar
Peterson, C. L., & Laniel, M. A. (2004). Histones and histone modifications. Current Biology, 14, R546–R551.CrossRefGoogle ScholarPubMed
Pruessner, J. C., Dedovic, K., Khalili-Mahani, N., Engert, V., Pruessner, M., Buss, C., et al. (2008). Deactivation of the limbic system during acute psychosocial stress: Evidence from positron emission tomography and functional magnetic resonance imaging studies. Biological Psychiatry, 63, 234–240.CrossRefGoogle ScholarPubMed
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., & Elbert, T. (2011). Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Translational Psychiatry, 1, e21.CrossRefGoogle ScholarPubMed
Razin, A. (1998). CpG methylation, chromatin structure and gene silencing: A three-way connection. EMBO Journal, 17, 4905–4908.CrossRefGoogle ScholarPubMed
Rettew, D. C., & McKee, L. (2005). Temperament and its role in developmental psychopathology. Harvard Review of Psychiatry, 13, 14–27.CrossRefGoogle ScholarPubMed
Rice, F., Harold, G. T., Boivin, J., Van den Bree, M., Hay, D. F., & Thapar, A. (2009). The links between prenatal stress and offspring development and psychopathology: Disentangling environmental and inherited influences. Psychological Medicine, 40, 335–345.CrossRefGoogle ScholarPubMed
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biological Psychiatry, 65, 760–769.CrossRefGoogle ScholarPubMed
Roth, T. L., & Sullivan, R. M. (2005). Memory of early maltreatment: Neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning. Biological Psychiatry, 57, 823–831.CrossRefGoogle ScholarPubMed
Sandman, C. A., Davis, E. P., Buss, C., & Glynn, L. M. (2011). Exposure to prenatal psychobiological stress exerts programming influences on the mother and her fetus. Neuroendocrinology, 95, 8–21.CrossRefGoogle ScholarPubMed
Sandman, C. A., Wadhwa, P. D., Chicz-DeMet, A., Porto, M., & Garite, T. J. (1999). Maternal corticotropin-releasing hormone and habituation in the human fetus. Developmental Psychobiology, 34, 163–173.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Schneider, M. L. (1992). The effect of mild stress during pregnancy on birthweight and neuromotor maturation in rhesus monkey infants (Macaca mulatta). Infant Behavior and Development, 15, 389–403.CrossRefGoogle Scholar
Schneider, M. L., Roughton, E. C., Koehler, A. J., & Lubach, G. R. (1999). Growth and development following prenatal stress exposure in primates: An examination of ontogenetic vulnerability. Child Development, 70, 263–274.CrossRefGoogle ScholarPubMed
Selten, J. P., Cantor-Graae, E., Nahon, D., Levav, I., Aleman, A., & Kahn, R. S. (2003). No relationship between risk of schizophrenia and prenatal exposure to stress during the Six-Day War or Yom Kippur War in Israel. Schizophrenia Research, 63, 131–135.CrossRefGoogle ScholarPubMed
Sitras, V., Paulssen, R., Leirvik, J., Vartun, A., & Acharya, G. (2009). Placental gene expression profile in intrauterine growth restriction due to placental insufficiency. Reproductive Sciences, 16, 701–711.CrossRefGoogle ScholarPubMed
Smith, F. M., Garfield, A. S., & Ward, A. (2006). Regulation of growth and metabolism by imprinted genes. Cytogenetic Genome Research, 113, 279–291.CrossRefGoogle ScholarPubMed
Spinelli, S., Chefer, S., Suomi, S. J., Higley, J. D., Barr, C. S., & Stein, E. (2009). Early-life stress induces long-term morphologic changes in primate brain. Archives of General Psychiatry, 66, 658–665.CrossRefGoogle ScholarPubMed
Stein, Z., Susser, M., Saenger, G., & Marolla, F. (1972). Nutrition and mental performance. Science, 178, 708–713.CrossRefGoogle ScholarPubMed
Suomi, S. J., Eisele, C. D., Grady, S. A., & Harlow, H. F. (1975). Depressive behavior in adult monkeys following separation from family environment. Journal of Abnormal Psychology, 84, 576–578.CrossRefGoogle ScholarPubMed
Suomi, S. J., Harlow, H. F., & Kimball, S. D. (1971). Behavioral effects of prolonged partial social isolation in the rhesus monkey. Psychological Reports, 29, 1171–1177.CrossRefGoogle ScholarPubMed
Susser, E., Hoek, H. W., & Brown, A. (1998). Neurodevelopmental disorders after prenatal famine: The story of the Dutch Famine Study. American Journal of Epidemiology, 147, 213–216.CrossRefGoogle ScholarPubMed
Susser, E. B., Brown, A., & Matte, T. D. (1999). Prenatal factors and adult mental and physical health. Canadian Journal of Psychiatry, 44, 326–334.CrossRefGoogle ScholarPubMed
Susser, E. S., & Lin, S. P. (1992). Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944–1945. Archives of General Psychiatry, 49, 983–988.CrossRefGoogle Scholar
Sutter-Dallay, A. L., Giaconne-Marcesche, V., Glatigny-Dallay, E., & Verdoux, H. (2004). Women with anxiety disorders during pregnancy are at increased risk of intense postnatal depressive symptoms: A prospective survey of the MATQUID cohort. European Psychiatry, 19, 459–463.CrossRefGoogle ScholarPubMed
Tabano, S., Colapietro, P., Cetin, I., Grati, F. R., Zanutto, S., Mando, C., et al. (2010). Epigenetic modulation of the IGF2/H19 imprinted domain in human embryonic and extra-embryonic compartments and its possible role in fetal growth restriction. Epigenetics, 5, 313–324.CrossRefGoogle ScholarPubMed
Takahashi, L. K., Baker, E. W., & Kalin, N. H. (1990). Ontogeny of behavioral and hormonal responses to stress in prenatallay stressed male rat pups. Physiology and Behavior, 47, 357–364.CrossRefGoogle ScholarPubMed
Takahashi, L. K., Haglin, C., & Kalin, N. H. (1992). Prenatal stress potentiates stress-induced behavior and reduces the propensity to play in juvenile rats. Physiology and Behavior, 51, 319–323.CrossRefGoogle ScholarPubMed
Talge, N. M., Neal, C., & Glover, V. (2007). Antenatal maternal stress and long-term effects on child neurodevelopment: How and why? Journal of Child Psychology and Psychiatry, 48, 245–261.CrossRefGoogle ScholarPubMed
Teti, D. M., Felfand, D. M., Messinger, D. S., & Isabella, R. (1995). Maternal depression and the quality of early attachment: An examination of intants, preschoolers, and their mothers. Developmental Psychobiology, 31, 364–376.CrossRefGoogle Scholar
Tobi, E. W., Lumey, L. H., Talens, R. P., Kremer, D., Putter, H., Stein, A. D., et al. (2009). DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Human Molecular Genetics, 18, 4046–4053.CrossRefGoogle ScholarPubMed
Tronick, E., & Gianino, A. (1986). The transmission of maternal disturbance to the infant. In Tronick, E. & Field, T. (Eds.), Maternal depression and infant disturbance (pp. 5–12). San Francisco, CA: Jossey–Bass.Google ScholarPubMed
Tronick, E. Z. (1989). Emotions and emotinal communication in infants. American Psychologist, 44, 112–119.CrossRefGoogle Scholar
Turek-Plewa, J., & Jagodzinski, P. P. (2005). The role of mammalian DNA methyltransferases in the regulation of gene expression. Cellular and Molecular Biology Letters, 10, 631–647.Google ScholarPubMed
Turner, B. (2001). Chromatin and gene regulation. Oxford: Blackwell Science.CrossRefGoogle Scholar
Tycko, B. (2006). Imprinted genes in placental growth and obstetric disorders. Cytogenetic and Genome Research, 113, 271–278.CrossRefGoogle ScholarPubMed
Umlauf, D., Goto, Y., & Feil, R. (2004). Site-specific analysis of histone methylation and acetylation. Methods in Molecular Biology, 287, 99–120.Google ScholarPubMed
Valentine, J. M., Rodriguez, M. A., Lapeyrouse, L. M., & Zhang, M. (2011). Recent intimate partner violence as a prenatal predictor of maternal depression in the first year postpartum among Latinas. Archives of Women's Mental Health, 14, 135–143.CrossRefGoogle ScholarPubMed
Van den Bergh, B. R., & Marcoen, A. (2004). High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems and anxiety in 8–9 year olds. Child Development, 75, 1085–1097.CrossRefGoogle Scholar
Van den Bergh, B. R., Mennes, M., Oosterlaan, J., Stevens, V., Stiers, P., Marcoen, A., et al. . (2005). High antenatal maternal anxiety is related to impulsivity during performance on cognitive tasks in 14- and 15-year-olds. Neuroscience & Biobehavioral Reviews, 29, 259–269.CrossRefGoogle ScholarPubMed
Van den Bergh, B. R., Mennes, M., Stevens, V., Van der Meere, J., Borger, N., Stiers, P., et al. . (2006). ADHD deficit as measured in adolescent boys with a continuous performance task is related to antenatal maternal anxiety. Pediatric Research, 59, 78–82.CrossRefGoogle ScholarPubMed
Van den Bergh, B. R., Van Calster, B., Smits, T., Van Huffel, S., & Lagae, L. (2008). Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: A prospective study on the fetal origins of depressed mood. Neuropsychopharmacology, 33, 536–545.CrossRefGoogle ScholarPubMed
Verkerk, G. J., Pop, V. J., Van Son, M. J., & Van Heck, G. L. (2003). Prediction of depression in the postpartum period: A longitudinal follow-up study in high-risk and low-risk women. Journal of Affective Disorders, 77, 159–166.CrossRefGoogle ScholarPubMed
Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847–854.CrossRefGoogle ScholarPubMed
Weaver, I. C., Champagne, F. A., Brown, S. E., Dymov, S., Sharma, S., Meaney, M. J., et al. (2005). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: Altering epigenetic marking later in life. Journal of Neuroscience, 25, 11045–11054.CrossRefGoogle ScholarPubMed
Weaver, I. C., Meaney, M. J., & Szyf, M. (2006). Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proceedings of the National Academy of Sciences, 103, 3480–3485.CrossRefGoogle ScholarPubMed
Weinstock, M. (2005). The potential influence of maternal stress hormones on development and mental health of the offspring. Brain, Behavior, and Immunity, 19, 296–308.CrossRefGoogle ScholarPubMed
Werner, A., Myers, M. M., Fifer, W. P., Cheng, B., Fang, Y., Allen, R., et al. (2007). Prenatal predictors of infant temperament. Developmental Psychobiology, 49, 474–484.CrossRefGoogle ScholarPubMed
Xu, W., Edmondson, D. G., Evrard, Y. A., Wakamiya, M., Behringer, R. R., & Roth, S. Y. (2000). Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development. Nature Genetics, 26, 229–232.CrossRefGoogle ScholarPubMed
Yao, T. P., Oh, S. P., Fuchs, M., Zhou, N. D., Ch'ng, L. E., Newsome, D., et al. (1998). Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell, 93, 361–372.CrossRefGoogle ScholarPubMed
Zeanah, C. H., Keener, M. A., Stewart, L., & Anders, T. F. (1985). Prenatal perception of infant personality: A preliminary investigation. Journal of the American Academy of Child & Adolescent Psychiatry, 24, 204–210.Google ScholarPubMed
Zekoski, E. M., O'Hara, M. W., & Wills, K. E. (1987). The effects of maternal mood on mother–infant interaction. Journal of Abnormal Child Psychology, 15, 361–378.CrossRefGoogle ScholarPubMed
Zhang, T. Y., Hellstrom, I. C., Bagot, R. C., Wen, X., Diorio, J., & Meaney, M. J. (2010). Maternal care and DNA methylation of a glutamic acid decarboxylase 1 promoter in rat hippocampus. Journal of Neuroscience, 30, 13130–13137.CrossRefGoogle ScholarPubMed