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Caregiver maltreatment causes altered neuronal DNA methylation in female rodents

  • Jennifer Blaze (a1) and Tania L. Roth (a1)

Abstract

Negative experiences with a caregiver during infancy can result in long-term changes in brain function and behavior, but underlying mechanisms are not well understood. It is our central hypothesis that brain and behavior changes are conferred by early childhood adversity through epigenetic changes involving DNA methylation. Using a rodent model of early-life caregiver maltreatment (involving exposure to an adverse caregiving environment for postnatal days 1–7), we have previously demonstrated abnormal methylation of DNA associated with the brain-derived neurotrophic factor (Bdnf) gene in the medial prefrontal cortex (mPFC) of adult rats. The aim of the current study was to characterize Bdnf DNA methylation in specific cell populations within the mPFC. In the prefrontal cortex, there is approximately twice as many neurons as glia, and studies have recently shown differential and distinctive DNA methylation patterns in neurons versus nonneurons. Here, we extracted nuclei from the mPFC of adult animals that had experienced maltreatment and used fluorescence-activated cell sorting to isolate cell types before performing bisulfite sequencing to estimate methylation of cytosine–guanine sites. Our data indicate that early-life stress induced methylation of DNA associated with Bdnf IV in a cell-type and sex-specific manner. Specifically, females that experienced early-life maltreatment exhibited greater neuronal cytosine–guanine methylation compared to controls, while no changes were detected in Bdnf methylation in males regardless of cell type. These changes localize the specificity of our previous findings to mPFC neurons and highlight the capacity of maltreatment to cause methylation changes that are likely to have functional consequences for neuronal function.

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Copyright

Corresponding author

Address correspondence and reprint requests to: Tania L. Roth, Department of Psychological and Brain Sciences, University of Delaware, 108 Wolf Hall, Newark, DE 19716; E-mail: troth@psych.udel.edu.

Footnotes

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This research was supported by NIGMS (1P20GM103653) and a University of Delaware Graduate Fellowship. We thank Dr. Robert Akins (Nemours-Alfred I. DuPont Hospital for Children), Dr. Jaclyn Schwarz (University of Delaware), Dr. Lynn Opdenaker (Center for Translational Cancer Research and Christiana Care Hospital), and Dr. Danay Baker-Andresen (University of Queensland) for their help with troubleshooting the fluorescence-activated cell sorting technique. We thank the Delaware Biotechnology Institute for the use of their core facilities (supported by the Delaware INBRE program, with Grant P20 GM103446 from NIGMS and the state of Delaware). We also thank Angela Maggio and Kristyn Borrelli for their assistance with behavioral coding.

Footnotes

References

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Aid, T., Kazantseva, A., Piirsoo, M., Palm, K., & Timmusk, T. (2007). Mouse and rat bdnf gene structure and expression revisited. Journal of Neuroscience Research, 85, 525535.
Alleva, E., & Santucci, D. (2001). Psychosocial vs. “physical” stress situations in rodents and humans: Role of neurotrophins. Physiology & Behavior, 73, 313320.
Asok, A., Bernard, K., Rosen, J. B., Dozier, M., & Roth, T. L. (2014). Infant-caregiver experiences alter telomere length in the brain. PLOS ONE, 9, e101437.
Azevedo, F. A., Carvalho, L. R., Grinberg, L. T., Farfel, J. M., Ferretti, R. E., Leite, R. E., … Herculano-Houzel, S. (2009). Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. Journal of Comparative Neurology, 513, 532541.
Bagot, R. C., van Hasselt, F. N., Champagne, D. L., Meaney, M. J., Krugers, H. J., & Joëls, M. (2009). Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus. Neurobiology of Learning and Memory, 92, 292300.
Bale, T. L., & Epperson, C. N. (2015). Sex differences and stress across the lifespan. Nature Neuroscience, 18, 14131420.
Bernard, K., Dozier, M., Bick, J., Lewis-Morrarty, E., Lindhiem, O., & Carlson, E. (2012). Enhancing attachment organization among maltreated children: Results of a randomized clinical trial. Child Development, 83, 623636.
Berthelot, N., Ensink, K., Bernazzani, O., Normandin, L., Luyten, P., & Fonagy, P. (2015). Intergenerational transmission of attachment in abused and neglected mothers: The role of trauma-specific reflective functioning. Infant Mental Health Journal, 36, 200212.
Bianchi, F. J., & Tanno, A. P. (2001). Determination of the estrous cycle phase of rats: Some helpful considerations. Brazilian Journal of Biology, 62, 609614.
Bilbo, S. D., Barrientos, R. M., Eads, A. S., Northcutt, A., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2008). Early-life infection leads to altered bdnf and IL-1β mRNA expression in rat hippocampus following learning in adulthood. Brain, Behavior, and Immunity, 22, 451455.
Blaze, J., Asok, A., & Roth, T. L. (2015). Long-term effects of early-life caregiving experiences on brain-derived neurotrophic factor histone acetylation in the adult rat mPFC. Stress, 18, 607615.
Blaze, J., & Roth, T. L. (2013). Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex. International Journal of Developmental Neuroscience, 31, 804810.
Blaze, J., & Roth, T. L. (2015). Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation. Seminars in Cell & Developmental Biology, 43, 7684.
Blaze, J., Scheuing, L., & Roth, T. L. (2013). Differential methylation of genes in the medial prefrontal cortex of developing and adult rats following exposure to maltreatment or nurturing care during infancy. Developmental Neuroscience, 35, 306316.
Bock, J., Rether, K., Groeger, N., Xie, L., & Braun, K. (2014). Perinatal programming of emotional brain circuits: An integrative view from systems to molecules. Frontiers in Neuroscience, 8, 11.
Bokhorst, C. L., Bakermans-Kranenburg, M. J., Pasco Fearon, R. M., van IJzendoorn, M. H., Fonagy, P., & Schuengel, C. (2003). The importance of shared environment in mother–infant attachment security: A behavioral genetic study. Child Development, 74, 17691782.
Boku, S., Toda, H., Nakagawa, S., Kato, A., Inoue, T., Koyama, T., … Kusumi, I. (2015). Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter. Biological Psychiatry, 77, 335344.
Bolton, J. L., Huff, N. C., Smith, S. H., Mason, S. N., Foster, W. M., Auten, R. L., & Bilbo, S. D. (2013). Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice. Environmental Health Perspectives, 12, 10751082.
Booth, M. J., Ost, T. W., Beraldi, D., Bell, N. M., Branco, M. R., Reik, W., & Balasubramanian, S. (2013). Oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine. Nature Protocols, 8, 18411851.
Braun, K., Lange, E., Metzger, M., & Poeggel, G. (1999). Maternal separation followed by early social deprivation affects the development of monoaminergic fiber systems in the medial prefrontal cortex of Octodon degus . Neuroscience, 95, 309318.
Caldji, C., Diorio, J., & Meaney, M. J. (2000). Variations in maternal care in infancy regulate the development of stress reactivity. Biological Psychiatry, 48, 11641174.
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, 53355340.
Caligioni, C. (2009). Assessing reproductive status/stages in mice. Current Protocols in Neuroscience, Appendix 4. doi:10.1002/0471142301.nsa04is48
Carpenter, L. L., Gawuga, C. E., Tyrka, A. R., Lee, J. K., Anderson, G. M., & Price, L. H. (2010). Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults. Neuropsychopharmacology, 35, 26172623.
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J., & Zoghbi, H. Y. (2008). Mecp2, a key contributor to neurological disease, activates and represses transcription. Science, 320, 12241229.
Chen, E. S., Ernst, C., & Turecki, G. (2011). The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression. International Journal of Neuropsychopharmacology, 14, 427429.
Chen, Y., Rex, C. S., Rice, C. J., Dubé, C. M., Gall, C. M., Lynch, G., & Baram, T. Z. (2010). Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling. Proceedings of the National Academy of Sciences, 107, 1312313128.
Chocyk, A., Bobula, B., Dudys, D., Przyborowska, A., Majcher-Maślanka, I., Hess, G., & Wędzony, K. (2013). Early-life stress affects the structural and functional plasticity of the medial prefrontal cortex in adolescent rats. European Journal of Neuroscience, 38, 20892107.
Cicchetti, D., & Rogosch, F. A. (2009). Adaptive coping under conditions of extreme stress: Multilevel influences on the determinants of resilience in maltreated children. New Directions for Child and Adolescent Development, 2009, 4759.
Cicchetti, D., Rogosch, F. A., Hecht, K. F., Crick, N. R., & Hetzel, S. (2014). Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes. Development and Psychopathology, 26, 831849.
Cicchetti, D., Rogosch, F., & Toth, S. L. (2006). Fostering secure attachment in infants in maltreating families through preventive interventions. Development and Psychopathology, 18, 623649.
Cicchetti, D., & Toth, S. L. (1995). A developmental psychopathology perspective on child abuse and neglect. Journal of the American Academy of Child & Adolescent Psychiatry, 34, 541565.
Cicchetti, D., & Toth, S. L. (2005). Child maltreatment. Annual Review of Clinical Psychology, 1, 409438.
Cirulli, F., Francia, N., Berry, A., Aloe, L., Alleva, E., & Suomi, S. J. (2009). Early life stress as a risk factor for mental health: Role of neurotrophins from rodents to non-human primates. Neuroscience & Biobehavioral Reviews, 33, 573585.
Cohen, R. A., Grieve, S., Hoth, K. F., Paul, R. H., Sweet, L., Tate, D., … Williams, L. M. (2006). Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biological Psychiatry, 59, 975982.
Coull, J. A. M., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., … De Koninck, Y. (2005). BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature, 438, 10171021.
Dozier, M., Stoval, K. C., Albus, K. E., & Bates, B. (2001). Attachment for infants in foster care: The role of caregiver state of mind. Child Development, 72, 14671477.
Dube, S. R., Anda, R. F., Whitfield, C. L., Brown, D. W., Felitti, V. J., Dong, M., & Giles, W. H. (2005). Long-term consequences of childhood sexual abuse by gender of victim. American Journal of Preventive Medicine, 28, 430438.
Essex, M. J., Thomas Boyce, W., Hertzman, C., Lam, L. L., Armstrong, J. M., Neumann, S. M. A., & Kobor, M. S. (2013). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Development, 84, 5875.
Ewald, E. R., Wand, G. S., Seifuddin, F., Yang, X., Tamashiro, K. L., Potash, J. B., … Lee, R. S. (2014). Alterations in DNA methylation of FKBP5 as a determinant of blood-brain correlation of glucocorticoid exposure. Psychoneuroendocrinology, 44, 112122.
Fisher, P. A., Gunnar, M. R., Dozier, M., Bruce, J., & Pears, K. C. (2006). Effects of therapeutic interventions for foster children on behavioral problems, caregiver attachment, and stress regulatory neural systems. Annals of the New York Academy of Sciences, 1094, 215225.
Francis, D., Diorio, J., Liu, D., & Meaney, M. J. (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 286, 11551158.
Franklin, T. B., Russig, H., Weiss, I. C., Graff, J., Linder, N., Michalon, A., Vizi, S., & Mansuy, I. M. (2010). Epigenetic transmission of the impact of early stress across generations. Biological Psychiatry, 68, 408415.
Fuchikami, M., Morinobu, S., Segawa, M., Okamoto, Y., Yamawaki, S., Ozaki, N., … Terao, T. (2011). DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLOS ONE, 6, e23881.
Gershon, A., Sudheimer, K., Tirouvanziam, R., Williams, L., & O'Hara, R. (2013). The long-term impact of early adversity on late-life psychiatric disorders. Current Psychiatry Reports, 15, 19.
Gorski, J. A., Zeiler, S. R., Tamowski, S., & Jones, K. R. (2003). Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. Journal of Neuroscience, 23, 68566865.
Guintivano, J., Aryee, M. J., & Kaminsky, Z. A. (2013). A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. Epigenetics, 8, 290302.
Gunnar, M. R., Frenn, K., Wewerka, S. S., & Van Ryzin, M. J. (2009). Moderate versus severe early life stress: Associations with stress reactivity and regulation in 10–12-year-old children. Psychoneuroendocrinology, 34, 6275.
Hao, Y., Huang, W., Nielsen, D. A., & Kosten, T. A. (2011). Litter gender composition and sex affect maternal behavior and DNA methylation levels of the oprm1 gene in rat offspring. Frontiers in Psychiatry, 2, 21.
Heim, C., & Nemeroff, C. B. (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biological Psychiatry, 49, 10231039.
Heim, C., Newport, D. J., Heit, S., Graham, Y. P., Wilcox, M., Bonsall, R., … Nemeroff, C. B. (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. Journal of the American Medical Association, 284, 592597.
Heim, C., Newport, D. J., Wagner, D., Wilcox, M. M., Miller, A. H., & Nemeroff, C. B. (2002). The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: A multiple regression analysis. Depression and Anxiety, 15, 117125.
Ikegame, T., Bundo, M., Sunaga, F., Asai, T., Nishimura, F., Yoshikawa, A., … Iwamoto, K. (2013). DNA methylation analysis of bdnf gene promoters in peripheral blood cells of schizophrenia patients. Neuroscience Research, 77, 208214.
Ivy, A. S., Brunson, K. L., Sandman, C., & Baram, T. Z. (2008). Dysfunctional nurturing behavior in rat dams with limited access to nesting material: A clinically relevant model for early-life stress. Neuroscience, 154, 11321142.
Ivy, A. S., Rex, C. S., Chen, Y., Dubé, C., Maras, P. M., Grigoriadis, D. E., … Baram, T. Z. (2010). Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors. Journal of Neuroscience, 30, 1300513015.
Iwamoto, K., Bundo, M., Ueda, J., Oldham, M. C., Ukai, W., Hashimoto, E., … Kato, T. (2011). Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome Research, 21, 688696.
Kawamoto, Y., Nakamura, S., Kawamata, T., Akiguchi, I., & Kimura, J. (1999). Cellular localization of brain-derived neurotrophic factor-like immunoreactivity in adult monkey brain. Brain Research, 821, 341349.
Keller, S., Sarchiapone, M., & Zarrilli, F. (2010). Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Archives of General Psychiatry, 67, 258267.
Kigar, S. L., Chang, L., Hayne, M. R., Karls, N. T., & Auger, A. P. (2016). Sex differences in Gadd45b expression and methylation in the developing rodent amygdala. Brain Research, 1642, 461466.
Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., & Moffitt, T. E. (2006). MAOA, maltreatment, and gene-environment interaction predicting children's mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11, 903913.
Kolodkin, M. H., & Auger, A. P. (2011). Sex difference in the expression of DNA methyltransferase 3a in the rat amygdala during development. Journal of Neuroendocrinology, 23, 577583.
Kozlenkov, A., Roussos, P., Timashpolsky, A., Barbu, M., Rudchenko, S., Bibikova, M., … Di Narzo, A. F. (2014). Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites. Nucleic Acids Research, 42, 109127.
Kundakovic, M., Lim, S., Gudsnuk, K., & Champagne, F. A. (2013). Sex-specific and strain-dependent effects of early life adversity on behavioral and epigenetic outcomes. Frontiers in Psychiatry, 4, 78.
Lee, J., Duan, W., & Mattson, M. P. (2002). Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. Journal of Neurochemistry, 82, 13671375.
Leventopoulos, M., Rüedi-Bettschen, D., Knuesel, I., Feldon, J., Pryce, C. R., & Opacka-Juffry, J. (2007). Long-term effects of early life deprivation on brain glia in fischer rats. Brain Research, 1142, 119126.
Li, X., Baker-Andresen, D., Zhao, Q., Marshall, V., & Bredy, T. W. (2014). Methyl cpg binding domain ultra-sequencing: A novel method for identifying inter-individual and cell-type-specific variation in DNA methylation. Genes, Brain and Behavior, 13, 721731.
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., … Ecker, J. R. (2013). Global epigenomic reconfiguration during mammalian brain development. Science, 341, 1237905.
Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., … Meaney, M. J. (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science, 277, 16591662.
Loman, M. M., & Gunnar, M. R. (2010). Early experience and the development of stress reactivity and regulation in children. Neuroscience & Biobehavioral Reviews, 34, 867876.
Lopez, J. P., Mamdani, F., Labonte, B., Beaulieu, M. M., Yang, J. P., Berlim, M. T., … Turecki, G. (2013). Epigenetic regulation of BDNF expression according to antidepressant response. Molecular Psychiatry, 18, 398399.
Lowell, A., Renk, K., & Adgate, A. H. (2014). The role of attachment in the relationship between child maltreatment and later emotional and behavioral functioning. Child Abuse & Neglect, 38, 14361449.
Lubin, F. D., Roth, T. L., & Sweatt, J. D. (2008). Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. Journal of Neuroscience, 28, 1057610586.
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience, 10, 434445.
Lutz, P.-E., & Turecki, G. (2014). DNA methylation and childhood maltreatment: From animal models to human studies. Neuroscience, 264, 142156.
Lyons-Ruth, K., Pechtel, P., Yoon, S. A., Anderson, C. M., & Teicher, M. H. (2016). Disorganized attachment in infancy predicts greater amygdala volume in adulthood. Behavioural Brain Research, 308, 8393.
Marmigère, F., Givalois, L., Rage, F., Arancibia, S., & Tapia-Arancibia, L. (2003). Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats. Hippocampus, 13, 646655.
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., … Sun, Y. E. (2003). DNA methylation-related chromatin remodeling in activity-dependent bdnf gene regulation. Science, 302, 890893.
Martinowich, K., Manji, H., & Lu, B. (2007). New insights into BDNF function in depression and anxiety. Nature Neuroscience, 10, 10891093.
Matevossian, A., & Akbarian, S. (2008). Neuronal nuclei isolation from human postmortem brain tissue. Journal of Visualized Experiments, 20, e914.
McCarthy, M. M., Auger, A. P., Bale, T. L., De Vries, G. J., Dunn, G. A., Forger, N. G., … Wilson, M. E. (2009). The epigenetics of sex differences in the brain. Journal of Neuroscience, 29, 1281512823.
McEwen, B. S. (2010). Stress, sex, and neural adaptation to a changing environment: Mechanisms of neuronal remodeling. Annals of the New York Academy of Sciences, 1204, 3859.
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342348.
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 11611192.
Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., … Binder, E. B. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences, 110, 83028307.
Melas, P. A., Wei, Y., Wong, C. C. Y., Sjöholm, L. K., Åberg, E., Mill, J., Schalling, M., … Lavebratt, C. (2013). Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. International Journal of Neuropsychopharmacology, 16, 15131528.
Mirescu, C., Peters, J. D., & Gould, E. (2004). Early life experience alters response of adult neurogenesis to stress. Nature Neuroscience, 7, 841846.
Monroy, E., Hernández-Torres, E., & Flores, G. (2010). Maternal separation disrupts dendritic morphology of neurons in prefrontal cortex, hippocampus, and nucleus accumbens in male rat offspring. Journal of Chemical Neuroanatomy, 40, 93101.
Monteggia, L. M., Barrot, M., Powell, C. M., Berton, O., Galanis, V., Gemelli, T., … Nestler, E. J. (2004). Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proceedings of the National Academy of Sciences, 101, 1082710832.
Monteggia, L. M., Luikart, B., Barrot, M., Theobold, D., Malkovska, I., Nef, S., … Nestler, E. J. (2007). Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biological Psychiatry, 61, 187197.
Moore, C. L., & Morelli, G. A. (1979). Mother rats interact differently with male amd female offspring. Journal of Comparative and Physiological Psychology, 93, 677684.
Moriceau, S., Shionoya, K., Jakubs, K., & Sullivan, R. M. (2009). Early-life stress disrupts attachment learning: The role of amygdala corticosterone, locus ceruleus corticotropin releasing hormone, and olfactory bulb norepinephrine. Journal of Neuroscience, 29, 1574515755.
Mueller, B. R., & Bale, T. L. (2008). Sex-specific programming of offspring emotionality after stress early in pregnancy. Journal of Neuroscience, 28, 90559065.
Muhammad, A., Carroll, C., & Kolb, B. (2012). Stress during development alters dendritic morphology in the nucleus accumbens and prefrontal cortex. Neuroscience, 216, 103109.
Nakajima, K., Honda, S., Tohyama, Y., Imai, Y., Kohsaka, S., & Kurihara, T. (2001). Neurotrophin secretion from cultured microglia. Journal of Neuroscience Research, 65, 322331.
Nakajima, K., & Kohsaka, S. (2001). Microglia: Activation and their significance in the central nervous system. Journal of Biochemistry, 130, 169175.
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, 143155.
Nishioka, M., Shimada, T., Bundo, M., Ukai, W., Hashimoto, E., Saito, T.Iwamoto, K. (2013). Neuronal cell-type specific DNA methylation patterns of the Cacna1c gene. International Journal of Developmental Neuroscience, 31, 8995.
Nugent, B. M., & McCarthy, M. M. (2011). Epigenetic underpinnings of developmental sex differences in the brain. Neuroendocrinology, 93, 150158.
Nugent, B. M., Wright, C. L., Shetty, A. C., Hodes, G. E., Lenz, K. M., Mahurkar, A., … McCarthy, M. M. (2015). Brain feminization requires active repression of masculinization via DNA methylation. Nature Neuroscience, 18, 690697.
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, 97106.
Parrish, R. R., Day, J. J., & Lubin, F. D. (2012). Direct bisulfite sequencing for examination of DNA methylation with gene and nucleotide resolution from brain tissues. Current Protocols in Neuroscience, 60, 17.
Pascual, R., & Zamora-Leon, S. P. (2007). Effects of neonatal maternal deprivation and postweaning environmental complexity on dendritic morphology of prefrontal pyramidal neurons in the rat. Acta Neurobiologiae Experimentalis, 67, 471479.
Perisic, T., Zimmermann, N., Kirmeier, T., Asmus, M., Tuorto, F., Uhr, M., … Zschocke, J. (2010). Valproate and amitriptyline exert common and divergent influences on global and gene promoter-specific chromatin modifications in rat primary astrocytes. Neuropsychopharmacology, 35, 792805.
Perroud, N., Paoloni-Giacobino, A., Prada, P., Olie, E., Salzmann, A., Nicastro, R., … Malafosse, A. (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: A link with the severity and type of trauma. Translational Psychiatry, 1, e59.
Perroud, N., Salzmann, A., Prada, P., Nicastro, R., Hoeppli, M. E., Furrer, S., … Malafosse, A. (2013). Response to psychotherapy in borderline personality disorder and methylation status of the bdnf gene. Translational Psychiatry, 3, e207.
Pickreign Stronach, E., Toth, S. L., Rogosch, F., Oshri, A., Manly, J. T., & Cicchetti, D. (2011). Child maltreatment, attachment security, and internal representations of mother and mother-child relationships. Child Maltreatment, 16, 137145.
Prados, J., Stenz, L., Courtet, P., Prada, P., Nicastro, R., Adouan, W., … Perroud, N. (2015). Borderline personality disorder and childhood maltreatment: A genome-wide methylation analysis. Genes, Brain and Behavior, 14, 177188.
Rasmusson, A. M., Shi, L., & Duman, R. (2002). Downregulation of BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock. Neuropsychopharmacology, 27, 133142.
Riggs, S. A., Cusimano, A. M., & Benson, K. M. (2011). Childhood emotional abuse and attachment processes in the dyadic adjustment of dating couples. Journal of Counseling Psychology, 58, 126138.
Riley, C., Cope, T., & Buck, C. (2004). CNS neurotrophins are biologically active and expressed by multiple cell types. Journal of Molecular Histology, 35, 771783.
Roisman, G. I., & Fraley, R. C. (2008). A behavior-genetic study of parenting quality, infant attachment security, and their covariation in a nationally representative sample. Developmental Psychology, 44, 831839.
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, 760769.
Roth, T. L., Matt, S., Chen, K., & Blaze, J. (2014). Bdnf DNA methylation modifications in the hippocampus and amygdala of male and female rats exposed to different caregiving environments outside the homecage. Developmental Psychobiology, 56, 17551763.
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, 823831.
Roth, T. L., Zoladz, P. R., Sweatt, J. D., & Diamond, D. M. (2011). Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder. Journal of Psychiatric Research, 45, 919926.
Schwarz, J. M., Hutchinson, M. R., & Bilbo, S. D. (2011). Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression. Journal of Neuroscience, 31, 1783517847.
Shah, P., Fonagy, P., & Strathearn, L. (2010). Is attachment transmitted across generations? The plot thickens. Clinical Child Psychology and Psychiatry, 15, 329345.
Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., … Binder, E. B. (2015). DNA extracted from saliva for methylation studies of psychiatric traits: Evidence tissue specificity and relatedness to brain. American Journal of Medical Genetics, 168, 3644.
Song, Y., Miyaki, K., Suzuki, T., Sasaki, Y., Tsutsumi, A., Kawakami, N., … Kan, C. (2014). Altered DNA methylation status of human brain derived neurotrophic factor gene could be useful as biomarker of depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 165, 357364.
Spiers, H., Hannon, E., Schalkwyk, L. C., Smith, R., Wong, C. C. Y., O'Donovan, M. C., … Mill, J. (2015). Methylomic trajectories across human fetal brain development. Genome Research, 25, 338352.
St.-Cyr, S., & McGowan, P. (2015). Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor. Frontiers in Behavioral Neuroscience, 9, 145.
Stenz, L., Zewdie, S., Laforge-Escarra, T., Prados, J., La Harpe, R., Dayer, A., … Aubry, J.-M. (2015). BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues. Neuroscience Research, 91, 17.
Styron, T., & Janoff-Bulman, R. (1997). Childhood attachment and abuse: Long-term effects on adult attachment, depression, and conflict resolution. Child Abuse & Neglect, 21, 10151023.
Sun, W., Zang, L., Shu, Q., & Li, X. (2014). From development to diseases: The role of 5-hmc in brain. Genomics, 104, 347351.
Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M. (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience & Biobehavioral Reviews, 27, 3344.
Teicher, M. H., & Samson, J. A. (2016). Annual research review: Enduring neurobiological effects of childhood abuse and neglect. Journal of Child Psychology and Psychiatry, 57, 241266.
Thompson, M., Kingree, J., & Desai, S. (2004). Gender differences in long-term health consequences of physical abuse of children: Data from a nationally representative survey. American Journal of Public Health, 94, 599604.
Trainor, B. C., Pride, M., Landeros, R. V., Knoblauch, N. W., Takahashi, E. Y., Silva, A. L., & Crean, K. C. (2011). Sex differences in social interaction behavior following social defeat stress in the monogamous california mouse (Peromyscus californicus). PLOS ONE, 6, e17405.
Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012). Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: Preliminary findings in healthy adults. PLOS ONE, 7, e30148.
Uchida, S., Hara, K., Kobayashi, A., Funato, H., Hobara, T., Otsuki, K., … Watanabe, Y. (2010). Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents. Journal of Neuroscience, 30, 1500715018.
Unternaehrer, E., Meyer, A. H., Burkhardt, S. C., Dempster, E., Staehli, S., Theill, N., … Meinlschmidt, G. (2015). Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women. Stress, 18, 451461.
Vythilingam, M., Heim, C., Newport, J., Miller, A. H., Anderson, E., Bronen, R., … Charney, D. S. (2002). Childhood trauma associated with smaller hippocampal volume in women with major depression. American Journal of Psychiatry, 159, 20722080.
Walton, E., Hass, J., Liu, J., Roffman, J. L., Bernardoni, F., Roessner, V., … Ehrlich, S. (2016). Correspondence of DNA methylation between blood and brain tissue and its application to schizophrenia research. Schizophrenia Bulletin, 42, 406414.
Wang, A., Nie, W., Li, H., Hou, Y., Yu, Z., Fan, Q., & Sun, R. (2014). Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency. PLOS ONE, 9, e94394.
Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., … Meaney, M. J. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847854.
Wei, R., Lin, C.-M., & Tu, Y.-Y. (2010). Strain-specific BDNF expression of rat primary astrocytes. Journal of Neuroimmunology, 220, 9098.
Weiss, I. C., Franklin, T. B., Vizi, S., & Mansuy, I. M. (2011). Inheritable effect of unpredictable maternal separation on behavioral responses in mice. Frontiers in Behavioral Neuroscience, 5, 3.
Willing, J., Kim, T., Brodsky, L., Cortes, L., & Juraska, J. M. (2014). Puberty-induced changes in neuron and glia number in the prefrontal cortex of male and female rats. Paper presented at the International Society for Developmental Psychobiology Annual Meeting, Washington, DC.
Wu, X., Chen, P. S., Dallas, S., Wilson, B., Block, M. L., Wang, C. C., … Hong, J.-S. (2008). Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. International Journal of Neuropsychopharmacology, 11, 11231134.
Zhang, J., Qin, L., & Zhao, H. (2013). Early repeated maternal separation induces alterations of hippocampus reelin expression in rats. Journal of Biosciences, 38, 2733.

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