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Epigenetic mechanisms in the development of behavior: Advances, challenges, and future promises of a new field

Published online by Cambridge University Press:  17 December 2013

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

In the past decade, there have been exciting advances in the field of behavioral epigenetics that have provided new insights into a biological basis of neural and behavioral effects of gene–environment interactions. It is now understood that changes in the activity of genes established through epigenetic alterations occur as a consequence of exposure to environmental adversity, social stress, and traumatic experiences. DNA methylation in particular has thus emerged as a leading candidate biological pathway linking gene–environment interactions to long-term and even multigenerational trajectories in behavioral development, including the vulnerability and resilience to psychopathology. This paper discusses what we have learned from research using animal models and from studies in which the translation of these findings has been made to humans. Studies concerning the significance of DNA methylation alterations in outcomes associated with stress exposure later in life and dysfunction in the form of neuropsychiatric disorders are highlighted, and several avenues of future research are suggested that promise to advance our understanding of epigenetics both as a mechanism by which the environment can contribute to the development of psychiatric disorders and as an avenue for more effective intervention and treatment strategies.

Type
Regular Articles
Information
Development and Psychopathology , Volume 25 , Issue 4pt2: Development and Psychopathology: A Vision Realized , November 2013 , pp. 1279 - 1291
Copyright
Copyright © Cambridge University Press 2013 

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References

Abdolmaleky, H. M., Cheng, K.-H., Faraone, S. V., Wilcox, M., Glatt, S. J., Gao, F., et al. (2006). Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Human Molecular Genetics, 15, 3132–3145.CrossRefGoogle Scholar
Abdolmaleky, H. M., Cheng, K. H., Russo, A., Smith, C. L., Faraone, S. V., Wilcox, M., et al. (2005). Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report. American Journal of Medical Genetics, 134, 60–66.Google Scholar
Abdolmaleky, H. M., Yaqubi, S., Papageorgis, P., Lambert, A. W., Ozturk, S., Sivaraman, V., et al. (2011). Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophrenia Research, 129, 183–190.CrossRefGoogle ScholarPubMed
Abel, T., & Zukin, R. S. (2008). Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Current Opinion in Pharmacology, 8, 57–64.CrossRefGoogle ScholarPubMed
Beach, S. R. H., Brody, G. H., Todorov, A. A., Gunter, T. D., & Philibert, R. A. (2011). Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: An examination of the Iowa adoptee sample. Psychosomatic Medicine, 73, 83–87.CrossRefGoogle ScholarPubMed
Birnbaum, L. S., & Jung, P. (2011). From endocrine disruptors to nanomaterials: Advancing our understanding of environmental health to protect public health. Health Affairs, 30, 814–822.CrossRefGoogle ScholarPubMed
Borghol, N., Suderman, M., McArdle, W., Racine, A., Hallett, M., Pembrey, M., et al. (2012). Associations with early-life socio-economic position in adult DNA methylation. International Journal of Epidemiology, 41, 62–74.CrossRefGoogle ScholarPubMed
Brooks, P., Marietta, C., & Goldman, D. (1996). DNA mismatch repair and DNA methylation in adult brain neurons. Journal of Neuroscience, 16, 939–945.CrossRefGoogle ScholarPubMed
Brown, S. E., Weaver, I. C. G., Meaney, M. J., & Szyf, M. (2008). Regional-specific global cytosine methylation and DNA methyltransferase expression in the adult rat hippocampus. NeuroScience Letters, 440, 49–53.CrossRefGoogle ScholarPubMed
Carrard, A., Salzmann, A., Malafosse, A., & Karege, F. (2011). Increased DNA methylation status of the serotonin receptor 5HTR1A gene promoter in schizophrenia and bipolar disorder. Journal of Affective Disorders, 132, 450–453.CrossRefGoogle ScholarPubMed
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J., et al. (2008). MECP2, a key contributor to neurological disease, activates and represses transcription. Science, 320, 1224–1229.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., & 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., Weaver, I., 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
Chang, S.-C., Koenen, K. C., Galea, S., Aiello, A. E., Soliven, R., Wildman, D. E., et al. (2012). Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit neighborhood health study. PLoS ONE, 7, e39184.Google ScholarPubMed
Chen, J., Evans, A. N., Liu, Y., Honda, M., Saavedra, J. M., & Aguilera, G. (2012). Maternal deprivation in rats is associated with corticotrophin-releasing hormone (CRH) promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood. Journal of Neuroendocrinology, 24, 1055–1064.CrossRefGoogle ScholarPubMed
Chen, Y., Zhang, J., Zhang, L., Shen, Y., & Xu, Q. (2012). Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia. Human Genetics, 131, 1081–1087.CrossRefGoogle ScholarPubMed
Chertkow-Deutsher, Y., Cohen, H., Klein, E., & Ben-Shachar, D. (2010). DNA methylation in vulnerability to post-traumatic stress in rats: Evidence for the role of the post-synaptic density protein Dlgap2. International Journal of Neuropsychopharmacology, 13, 347–359.CrossRefGoogle ScholarPubMed
Cicchetti, D. (1993). Developmental psychopathology: Reactions, reflections, projections. Developmental Review, 13, 471–502.CrossRefGoogle Scholar
Cicchetti, D. (2006). Development and psychopathology. In Cicchetti, D. & Cohen, D. (Eds.), Developmental psychopathology (2nd ed., pp. 1–23). Hoboken, NJ: Wiley.Google ScholarPubMed
Connor, C. M., & Akbarian, S. (2008). DNA methylation changes in schizophrenia and bipolar disorder. Epigenetics, 3, 55–58.CrossRefGoogle ScholarPubMed
Crews, D., Gillette, R., Scarpino, S. V., Manikkam, M., Savenkova, M. I., & Skinner, M. K. (2012). Epigenetic transgenerational inheritance of altered stress responses. Proceedings of the National Academy of Sciences, 109, 9143–9148.CrossRefGoogle ScholarPubMed
Crudo, A., Petropoulos, S., Moisiadis, V. G., Iqbal, M., Kostaki, A., Machnes, Z., et al. (2012). Prenatal synthetic glucocorticoid treatment changes DNA methylation states in male organ systems: Multigenerational effects. Endocrinology, 153, 3269–3283.CrossRefGoogle ScholarPubMed
Davies, M., Volta, M., Pidsley, R., Lunnon, K., Dixit, A., Lovestone, S., et al. (2012). Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biology, 13, R43.CrossRefGoogle ScholarPubMed
Dempster, E. L., Pidsley, R., Schalkwyk, L. C., Owens, S., Georgiades, A., Kane, F., et al. (2011). Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Human Molecular Genetics, 20, 4786–4796.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
Dietz, D. M., LaPlant, Q., Watts, E. L., Hodes, G. E., Russo, S. J., Feng, J., et al. (2011). Paternal transmission of stress-induced pathologies. Biological Psychiatry, 70, 408–414.CrossRefGoogle ScholarPubMed
Drake, A. J., McPherson, R. C., Godfrey, K. M., Cooper, C., Lillycrop, K. A., Hanson, M., et al. (2012). An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth. Clinical Endocrinology, 77, 808–815.CrossRefGoogle Scholar
Dunn, G. A., & Bale, T. L. (2011). Maternal high-fat diet effects on third-generation female body size via the paternal lineage. Endocrinology, 152, 2228–2236.CrossRefGoogle ScholarPubMed
Elliott, E., Ezra-Nevo, G., Regev, L., Neufeld-Cohen, A., & Chen, A. (2010). Resilience to social stress coincides with functional DNA methylation of the CRF gene in adult mice. Nature Neuroscience, 13, 1351–1353.CrossRefGoogle ScholarPubMed
Essex, M. J., Thomas Boyce, W., Hertzman, C., Lam, L. L., Armstrong, J. M., Neumann, S. M., et al. (2011). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Development, 84, 58–75.CrossRefGoogle ScholarPubMed
Feng, J., Chang, H., Li, E., & Fan, G. (2005). Dynamic expression of de novo DNA methyltransferases DNMT3A and DNMT3B in the central nervous system. Journal of Neuroscience Research 79, 734–746.CrossRefGoogle ScholarPubMed
Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., et al. (2010). Epigenetic transmission of the impact of early stress across generations. Biological Psychiatry, 68, 408–415.CrossRefGoogle Scholar
Fuchikami, M., Morinobu, S., Segawa, M., Okamoto, Y., Yamawaki, S., Ozaki, N., et al. (2011). DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS ONE, 6, e23881.CrossRefGoogle ScholarPubMed
Ghadirivasfi, M., Nohesara, S., Ahmadkhaniha, H.-R., Eskandari, M.-R., Mostafavi, S., Thiagalingam, S., et al. (2011). Hypomethylation of the serotonin receptor type-2a gene (HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder. American Journal of Medical Genetics, 156B, 536–545.Google ScholarPubMed
Goto, K., Numata, M., Komura, J. I., Ono, T., Bestor, T. H., & Kondo, H. (1994). Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice. Differentiation, 56, 39–44.CrossRefGoogle ScholarPubMed
Govorko, D., Bekdash, R. A., Zhang, C., & Sarkar, D. K. (2012). Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biological Psychiatry, 72, 378–388.CrossRefGoogle Scholar
Grayson, D., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C., Guidotti, A., et al. (2005). Reelin promoter hypermethylation in schizophrenia. Proceedings of the National Academy of Sciences, 102, 9341–9346.CrossRefGoogle ScholarPubMed
Guidotti, A., Ruzicka, W., Grayson, D. R., Veldic, M., Pinna, G., Davis, J. M., et al. (2007). S-Adenosyl methionine and DNA methyltransferase-1 mRNA overexpression in psychosis. NeuroReport, 18, 57–60.CrossRefGoogle ScholarPubMed
Hackman, D. A., Farah, M. J., & Meaney, M. J. (2010). Socioeconomic status and the brain: Mechanistic insights from human and animal research. Nature Reviews Neuroscience, 11, 651–659.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Higuchi, F., Uchida, S., Yamagata, H., Otsuki, K., Hobara, T., Abe, N., et al. (2011). State-dependent changes in the expression of DNA methyltransferases in mood disorder patients. Journal of Psychiatric Research, 45, 1295–1300.CrossRefGoogle ScholarPubMed
Huang, H.-S., & Akbarian, S. (2007). GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PLoS ONE, 2, e809.CrossRefGoogle ScholarPubMed
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, 1132–1142.CrossRefGoogle ScholarPubMed
Iwamoto, K., Bundo, M., Ueda, J., Oldham, M. C., Ukai, W., Hashimoto, E., et al. (2011). Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome Research, 21, 688–696.CrossRefGoogle ScholarPubMed
Jensen Peña, C., Monk, C., & Champagne, F. A. (2012). Epigenetic effects of prenatal stress on 11β-hydroxysteroid dehydrogenase–2 in the placenta and fetal brain. PLoS ONE, 7, e39791.CrossRefGoogle ScholarPubMed
Keller, S., Sarchiapone, M., Zarrilli, F., Videtic, A., Ferraro, A., Carli, V., et al. (2010). Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Archives of General Psychiatry, 67, 258–267.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
Kinnally, E. L., Feinberg, C., Kim, D., Ferguson, K., Leibel, R., Coplan, J. D., et al. (2011). DNA methylation as a risk factor in the effects of early life stress. Brain, Behavior, and Immunity, 25, 1548–1553.CrossRefGoogle ScholarPubMed
Koenen, K. C., Uddin, M., Chang, S.-C., Aiello, A. E., Wildman, D. E., Goldmann, E., et al. (2011). SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder. Depression and Anxiety, 28, 639–647.CrossRefGoogle ScholarPubMed
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, 577–583.CrossRefGoogle ScholarPubMed
Korosi, A., Shanabrough, M., McClelland, S., Liu, Z.-W., Borok, E., Gao, X.-B., et al. (2010). Early-life experience reduces excitation to stress-responsive hypothalamic neurons and reprograms the expression of corticotropin-releasing hormone. Journal of Neuroscience, 30, 703–713.CrossRefGoogle ScholarPubMed
Kurian, J. R., Forbes-Lorman, R. M., & Auger, A. P. (2007). Sex difference in MECP2 expression during a critical period of rat brain development. Epigenetics, 2, 173–178.CrossRefGoogle ScholarPubMed
Labonté, B., Suderman, M., Maussion, G., Navaro, L., Yerko, V., Mahar, I., et al. (2012). Genome-wide epigenetic regulation by early-life trauma. Archives of General Psychiatry, 69, 722–731.CrossRefGoogle ScholarPubMed
Labonté, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., et al. (2012). Differential glucocorticoid receptor Exon 1B, 1C, and 1H expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry, 72, 41–48.CrossRefGoogle ScholarPubMed
Ladd-Acosta, C., Pevsner, J., Sabunciyan, S., Yolken, R. H., Webster, M. J., Dinkins, T., et al. (2007). DNA methylation signatures within the human brain. American Journal of Human Genetics, 81, 1304–1315.CrossRefGoogle ScholarPubMed
LaPlant, Q., Vialou, V., Covington, H. E., Dumitriu, D., Feng, J., Warren, B. L., et al. (2010). DNMT3A regulates emotional behavior and spine plasticity in the nucleus accumbens. Nature Neuroscience, 13, 1137–1143.CrossRefGoogle ScholarPubMed
Lott, S. A., Burghardt, P. R., Burghardt, K. J., Bly, M. J., Grove, T. B., & Ellingrod, V. L. (2012). The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia. Pharmacogenomics Journal. Advance online publication.Google ScholarPubMed
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, 10576–10586.CrossRefGoogle ScholarPubMed
Ma, D. K., Jang, M.-H., Guo, J. U., Kitabatake, Y., Chang, M.-L., Pow-Anpongkul, N., et al. (2009). Neuronal activity–induced GADD45B promotes epigenetic DNA demethylation and adult neurogenesis. Science, 323, 1074–1077.CrossRefGoogle ScholarPubMed
Matrisciano, F., Tueting, P., Dalal, I., Kadriu, B., Grayson, D. R., Davis, J. M., et al. (2012). Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology. Advance online publication.Google ScholarPubMed
Matsuda, K. I., Mori, H., Nugent, B. M., Pfaff, D. W., McCarthy, M. M., & Kawata, M. (2011). Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior. Endocrinology, 152, 2760–2767.CrossRefGoogle ScholarPubMed
McClelland, S., Korosi, A., Cope, J., Ivy, A., & Baram, T. Z. (2011). Emerging roles of epigenetic mechanisms in the enduring effects of early-life stress and experience on learning and memory. Neurobiology of Learning and Memory, 96, 79–88.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
McGowan, P. O., Sasaki, A., Huang, T. C. T., Unterberger, A., Suderman, M., Ernst, C., et al. (2008). Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS ONE, 3, e2085.CrossRefGoogle ScholarPubMed
McGowan, P. O., Suderman, M., Sasaki, A., Huang, T. C. T., Hallett, M., Meaney, M. J., et al. (2011). Broad epigenetic signature of maternal care in the brain of adult rats. PLoS ONE, 6, e14739.CrossRefGoogle ScholarPubMed
Melas, P. A., Rogdaki, M., Ösby, U., Schalling, M., Lavebratt, C., & Ekström, T. J. (2012). Epigenetic aberrations in leukocytes of patients with schizophrenia: Association of global DNA methylation with antipsychotic drug treatment and disease onset. FASEB Journal, 26, 2712–2718.CrossRefGoogle ScholarPubMed
Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., et al. (2008). Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. American Journal of Human Genetics, 82, 696–711.CrossRefGoogle ScholarPubMed
Miller, C. A., Gavin, C. F., White, J. A., Parrish, R. R., Honasoge, A., Yancey, C. R., et al. (2010). Cortical DNA methylation maintains remote memory. Nature Neuroscience, 13, 664–666.CrossRefGoogle ScholarPubMed
Miller, C. A., & Sweatt, J. D. (2007). Covalent mdification of DNA regulates memory formation. Neuron, 53, 857–869.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
Mychasiuk, R., Ilnytskyy, S., Kovalchuk, O., Kolb, B., & Gibb, R. (2011). Intensity matters: Brain, behaviour and the epigenome of prenatally stressed rats. Neuroscience, 180, 105–110.CrossRefGoogle ScholarPubMed
Mychasiuk, R., Schmold, N., Ilnytskyy, S., Kovalchuk, O., Kolb, B., & Gibb, R. (2011). Prenatal bystander stress alters brain, behavior, and the epigenome of developing rat offspring. Developmental Neuroscience, 33, 159–169.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
Nohesara, S., Ghadirivasfi, M., Mostafavi, S., Eskandari, M.-R., Ahmadkhaniha, H., Thiagalingam, S., et al. (2011). DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. Journal of Psychiatric Research, 45, 1432–1438.CrossRefGoogle ScholarPubMed
Numata, S., Ye, T., Hyde, Thomas M., Guitart-Navarro, X., Tao, R., et al. (2012). DNA methylation signatures in development and aging of the human prefrontal cortex. American Journal of Human Genetics, 90, 260–272.CrossRefGoogle ScholarPubMed
Oberlander, T., 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
Penner, M. R., Roth, T. L., Chawla, M. K., Hoang, L. T., Roth, E. D., Lubin, F. D., et al. (2010). Age-related changes in arc transcription and DNA methylation within the hippocampus. Neurobiology of Aging, 32, 2198–2210.CrossRefGoogle ScholarPubMed
Poulter, M. O., Du, L., Weaver, I. C. G., Palkovits, M., Faludi, G., Merali, Z., et al. (2008). GABAA receptor promoter hypermethylation in suicide brain: Implications for the involvement of epigenetic processes. Biological Psychiatry, 64, 645–652.CrossRefGoogle ScholarPubMed
Qin, L., Tu, W., Sun, X., Zhang, J., Chen, Y., & Zhao, H. (2011). Retardation of neurobehavioral development and reelin down-regulation regulated by further DNA methylation in the hippocampus of the rat pups are associated with maternal deprivation. Behavioural Brain Research, 217, 142–147.CrossRefGoogle ScholarPubMed
Raineki, C., Cortés, M. R., Belnoue, L., & Sullivan, R. M. (2012). Effects of early-life abuse differ across development: Infant social behavior deficits are followed by adolescent depressive-like behaviors mediated by the amygdala. Journal of Neuroscience, 32, 7758–7765.CrossRefGoogle ScholarPubMed
Ressler, K. J., Mercer, K. B., Bradley, B., Jovanovic, T., Mahan, A., Kerley, K., et al. (2011). Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature, 470, 492–497.CrossRefGoogle ScholarPubMed
Rodrigues, A. J., Leao, P., Pego, J. M., Cardona, D., Carvalho, M. M., Oliveira, M., et al. (2011). Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids. Molecular Psychiatry, 17, 1295–1305.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 cortent of classical conditioning. Biological Psychiatry, 57, 823–831.CrossRefGoogle ScholarPubMed
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, 919–926.CrossRefGoogle Scholar
Rothstein, M. A., Cai, Y., & Marchant, G. E. (2009). Ethical implications of epigenetics research. Nature Genetics, 10, 224.Google ScholarPubMed
Rusiecki, J. A., Chen, L., Srikantan, V., Zhang, L., Yan, L., Polin, M. L., et al. (2012). DNA methylation in repetitive elements and post-traumatic stress disorder: A case–control study of US military service members. Epigenomics, 4, 29–40.CrossRefGoogle ScholarPubMed
Ruzicka, W. B., Zhubi, A., Veldic, M., Grayson, D. R., Costa, E., & Guidotti, A. (2007). Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection. Molecular Psychiatry, 12, 385–397.CrossRefGoogle ScholarPubMed
Sabunciyan, S., Aryee, M. J., Irizarry, R. A., Rongione, M., Webster, M. J., Kaufman, W. E., et al. (2012). Genome-wide DNA methylation scan in major depressive disorder. PLoS ONE, 7, e34451.CrossRefGoogle ScholarPubMed
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, 17835–17847.CrossRefGoogle ScholarPubMed
Schwarz, J. M., Nugent, B. M., & McCarthy, M. M. (2010). Developmental and hormone-induced epigenetic changes to estrogen and progesterone receptor genes in brain are dynamic across the life span. Endocrinology, 151, 4871–4881.CrossRefGoogle ScholarPubMed
Siegmund, K. D., & Connor, C. M. (2007). DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS ONE, 2, e895.CrossRefGoogle ScholarPubMed
Skinner, M. K., Anway, M. D., Savenkova, M. I., Gore, A. C., & Crews, D. (2008). Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior. PLoS ONE, 3, e3745.CrossRefGoogle ScholarPubMed
Smith, A. K., Conneely, K. N., Kilaru, V., Mercer, K. B., Weiss, T. E., Bradley, B., et al. (2011). Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. American Journal of Medical Genetics, 156B, 700–708.Google ScholarPubMed
Sroufe, L. A., & Rutter, M. (1984). The domain of developmental psychopathology. Child Development, 55, 17–29.CrossRefGoogle ScholarPubMed
Sterrenburg, L., Gaszner, B., Boerrigter, J., Santbergen, L., Bramini, M., Elliott, E., et al. (2011). Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat. PLoS ONE, 6, e28128.CrossRefGoogle ScholarPubMed
Suter, M., Ma, J., Harris, A. S., Patterson, L., Brown, K. A., Shope, C., et al. (2011). Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression. Epigenetics, 6, 1284–1294.CrossRefGoogle ScholarPubMed
Tung, J., Barreiro, L. B., Johnson, Z. P., Hansen, K. D., Michopoulos, V., Toufexis, D., et al. (2012). Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proceedings of the National Academy of Sciences, 109, 6490–6495.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Uchida, S., Hara, K., Kobayashi, A., Otsuki, K., Yamagata, H., Hobara, T., et al. (2011). Epigenetic status of GDNF in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron, 69, 359–372.CrossRefGoogle ScholarPubMed
Uddin, M., Aiello, A. E., Wildman, D. E., Koenen, K. C., Pawelec, G., de los Santos, R., et al. (2010). Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences, 107, 9470–9475.CrossRefGoogle ScholarPubMed
Uddin, M., Galea, S., Chang, S.-C., Aiello, A. E., Wildman, D. E., de los Santos, R., et al. (2011). Gene expression and methylation signatures of MAN2C1 are associated with PTSD. Disease Markers, 30, 111–121.CrossRefGoogle ScholarPubMed
Uddin, M., Koenen, K. C., Aiello, A. E., Wildman, D. E., de los Santos, R., & Galea, S. (2011). Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample. Psychological Medicine, 41, 997–1007.CrossRefGoogle Scholar
Unternaehrer, E., Luers, P., Mill, J., Dempster, E., Meyer, A. H., Staehli, S., et al. (2012). Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Translational Psychiatry, 2, e150.CrossRefGoogle ScholarPubMed
Ursini, G., Bollati, V., Fazio, L., Porcelli, A., Iacovelli, L., Catalani, A., et al. (2011). Stress-related methylation of the catechol-O-methyltransferase Val158 allele predicts human prefrontal cognition and activity. Journal of Neuroscience, 31, 6692–6698.CrossRefGoogle ScholarPubMed
Veldic, M., Caruncho, H. J., Liu, W. S., Davis, J., Satta, R., Grayson, D. R., et al. (2004). DNA-methyltransferase 1 MRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proceedings of the National Academy of Sciences, 101, 348–353.CrossRefGoogle ScholarPubMed
Veldic, M., Guidotti, A., Maloku, E., Davis, J. M., & Costa, E. (2005). In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proceedings of the National Academy of Sciences, 102, 2152–2157.CrossRefGoogle ScholarPubMed
Veldic, M., Kadriu, B., Maloku, E., Agis-Balboa, R. C., Guidotti, A., Davis, J. M., et al. (2007). Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder. Schizophrenia Research, 91, 51–61.CrossRefGoogle ScholarPubMed
Vijayendran, M., Beach, S., Plume, J. M., Brody, G., & Philibert, R. (2012). Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter. Frontiers in Psychiatry, 3, 55.CrossRefGoogle ScholarPubMed
Vucetic, Z., Kimmel, J., Totoki, K., Hollenbeck, E., & Reyes, T. M. (2010). Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology, 151, 4756–4764.CrossRefGoogle ScholarPubMed
Wang, H., Meyer, K., & Korz, V. (2012). Stress induced hippocampal mineralocorticoid and estrogen receptor β gene expression and long-term potentiation in male adult rats is sensitive to early-life stress experience. Psychoneuroendocrinology, 38, 250–262.CrossRefGoogle ScholarPubMed
Weaver, I. C. G., 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
Westberry, J. M., Trout, A. L., & Wilson, M. E. (2010). Epigenetic regulation of estrogen receptor α gene expression in the mouse cortex during early postnatal development. Endocrinology, 151, 731–740.CrossRefGoogle ScholarPubMed
Wilhelm-Benartzi, C. S., Houseman, E. A., Maccani, M. A., Poage, G. M., Koestler, D. C., Langevin, S. M., et al. (2011). In utero exposures, infant growth, and DNA methylation of repetitive elements and developmentally related genes in human placenta. Environmental Health Perspectives, 120, 296–302.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
Zill, P., Baghai, T. C., Schüle, C., Born, C., Früstück, C., Büttner, A., et al. (2012). DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PLoS ONE, 7, e40479.CrossRefGoogle ScholarPubMed
Zoladz, P. R., Conrad, C. D., Fleshner, M., & Diamond, D. M. (2008). Acute episodes of predator exposure in conjunction with chronic social instability as an animal model of post-traumatic stress disorder. Stress, 11, 259–281.CrossRefGoogle ScholarPubMed
Zoladz, P. R., Fleshner, M., & Diamond, D. M. (2012). Psychosocial animal model of PTSD produces a long-lasting traumatic memory, an increase in general anxiety and PTSD-like glucocorticoid abnormalities. Psychoneuroendocrinology, 37, 1531–1545.CrossRefGoogle ScholarPubMed