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Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes

Published online by Cambridge University Press:  02 February 2015

Li Chen
Affiliation:
Singapore Institute for Clinical Sciences
Hong Pan
Affiliation:
Singapore Institute for Clinical Sciences Nanyang Technological University
Ta Anh Tuan
Affiliation:
National University of Singapore
Ai Ling Teh
Affiliation:
Singapore Institute for Clinical Sciences
Julia L. MacIsaac
Affiliation:
University of British Columbia
Sarah M. Mah
Affiliation:
University of British Columbia
Lisa M. McEwen
Affiliation:
University of British Columbia
Yue Li
Affiliation:
National University of Singapore
Helen Chen
Affiliation:
KK Women's and Children's Hospital, Singapore
Birit F. P. Broekman
Affiliation:
Singapore Institute for Clinical Sciences National University Health System, Singapore
Jan Paul Buschdorf
Affiliation:
Singapore Institute for Clinical Sciences
Yap Seng Chong
Affiliation:
Singapore Institute for Clinical Sciences National University Health System, Singapore
Kenneth Kwek
Affiliation:
KK Women's and Children's Hospital, Singapore Duke–National University of Singapore
Seang Mei Saw
Affiliation:
National University of Singapore National University Health System, Singapore
Peter D. Gluckman
Affiliation:
Singapore Institute for Clinical Sciences University of Auckland
Marielle V. Fortier
Affiliation:
KK Women's and Children's Hospital, Singapore
Anne Rifkin-Graboi
Affiliation:
Singapore Institute for Clinical Sciences
Michael S. Kobor
Affiliation:
University of British Columbia
Anqi Qiu
Affiliation:
Singapore Institute for Clinical Sciences National University of Singapore
Michael J. Meaney
Affiliation:
Singapore Institute for Clinical Sciences McGill University
Joanna D. Holbrook
Affiliation:
Singapore Institute for Clinical Sciences

Abstract

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

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Special Section Articles
Copyright
Copyright © Cambridge University Press 2015 

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References

Abelson, J. L., Khan, S., Liberzon, I., & Young, E. A. (2007). HPA axis activity in patients with panic disorder: Review and synthesis of four studies. Depression and Anxiety, 24, 6676.CrossRefGoogle ScholarPubMed
Aguilera, M., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J., Villa, H., et al. (2009). Early adversity and 5-HTT/BDNF genes: New evidence of gene–environment interactions on depressive symptoms in a general population. Psychological Medicine, 39, 14251432.CrossRefGoogle Scholar
Alexander, N., Osinsky, R., Schmitz, A., Mueller, E., Kuepper, Y., & Hennig, J. (2010). The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress. Psychoneuroendocrinology, 35, 949953.CrossRefGoogle ScholarPubMed
Barton, S. J., Crozier, S. R., Lillycrop, K. A., Godfrey, K. M., & Inskip, H. M. (2013). Correction of unexpected distributions of p values from analysis of whole genome arrays by rectifying violation of statistical assumptions. BMC Genomics, 14, 161.CrossRefGoogle ScholarPubMed
Bateson, P., Barker, D., Clutton-Brock, T., Deb, D., Udine, B., Foley, R. A., et al. (2004). Developmental plasticity and human health. Nature, 430, 419421.CrossRefGoogle ScholarPubMed
Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2007). For better and for worse: Differential susceptibility to environmental influences. Current Directions in Psychological Science, 16, 300304.CrossRefGoogle Scholar
Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B., & Williams, R. (2009). Vulnerability genes or plasticity genes? Molecular Psychiatry, 14, 746754.CrossRefGoogle ScholarPubMed
Binder, E. B., Bradley, R. G., Liu, W., Epstein, M. P., Deveau, T. C., Mercer, K. B., et al. (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. Journal of the American Medical Association, 299, 12911305.CrossRefGoogle ScholarPubMed
Boyce, W. T., & Ellis, B. J. (2005). Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and functions of stress reactivity. Development and Psychopathology, 17, 271301.CrossRefGoogle ScholarPubMed
Bradley, R. H., & Corwyn, R. F. (2008). Infant temperament, parenting, and externalizing behavior in first grade: A test of the differential susceptibility hypothesis. Journal of Child Psychology and Psychiatry and Allied Discipline, 49, 124131.Google ScholarPubMed
Bromer, C., Marsit, C. J., Armstrong, D. A., Padbury, J. F., & Lester, B. (2013). Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1) in placenta and infant neurobehavior. Developmental Psychobiology, 55, 673683.Google 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, 141153.CrossRefGoogle ScholarPubMed
Buss, C., Davis, E. P., Shahbaba, B., Pruessner, J. C., Head, K., & Sandman, C. A. (2012). Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proceedings of the National Academy of Sciences, 109, E1312E1319.CrossRefGoogle ScholarPubMed
Carver, C. S., Johnson, S. L., Joormann, J., Lemoult, J., & Cuccaro, M. L. (2011). Childhood adversity interacts separately with 5-HTTLPR and BDNF to predict lifetime depression diagnosis. Journal of Affective Disorders, 132, 8993.CrossRefGoogle ScholarPubMed
Casey, B. J., Glatt, C. E., Tottenham, N., Soliman, F., Bath, K., Amso, D., et al. (2009). Brain-derived neurotrophic factor as a model system for examining gene by environment interactions across development. Neuroscience, 164, 108120.CrossRefGoogle ScholarPubMed
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509527.CrossRefGoogle ScholarPubMed
Champagne, F. A. (2012). Interplay between social experiences and the genome: Epigenetic consequences for behavior. Advances in Genetics, 77, 3357.Google ScholarPubMed
Chen, J., Li, X., & McGue, M. (2013). The interacting effect of the BDNF Val66Met polymorphism and stressful life events on adolescent depression is not an artifact of gene–environment correlation: Evidence from a longitudinal twin study. Journal of Child Psychology and Psychiatry and Allied Disciplines, 54, 10661073.CrossRefGoogle Scholar
Chen, Z. Y., Ieraci, A., Teng, H., Dall, H., Meng, C. X., Herrera, D. G., et al. (2005). Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. Journal of Neuroscience, 25, 61566166.CrossRefGoogle ScholarPubMed
Chen, Z. Y., Jing, D., Bath, K. G., Ieraci, A., Khan, T., Siao, C. J., et al. (2006). Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science, 314, 140143.CrossRefGoogle ScholarPubMed
Clarke, A. S., & Schneider, M. L. (1993). Prenatal stress has long-term effects on behavioral responses to stress in juvenile rhesus monkeys. Developmental Psychobiology, 26, 293304.CrossRefGoogle ScholarPubMed
Coe, C. L., Kramer, M., Czeh, B., Gould, E., Reeves, A. J., Kirschbaum, C., et al. (2003). Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biological Psychiatry, 54, 10251034.CrossRefGoogle ScholarPubMed
Davies, M. N., Krause, L., Bell, J. T., Gao, F., Ward, K. J., Wu, H., et al. (2014). Hypermethylation in the ZBTB20 gene is associated with major depressive disorder. Genome Biology, 15, R56.CrossRefGoogle ScholarPubMed
Dedeurwaerder, S., Defrance, M., Calonne, E., Denis, H., Sotiriou, C., & Fuks, F. (2011). Evaluation of the Infinium Methylation 450 K technology. Epigenomics, 3, 771784.CrossRefGoogle Scholar
Dennis, C. L., Coghlan, M., & Vigod, S. (2013). Can we identify mothers at risk for postpartum anxiety in the immediate postpartum period using the State–Trait Anxiety Inventory? Journal of Affective Disorders, 150, 12171220.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
Duman, R. S., & Monteggia, L. M. (2006). A neurotrophic model for stress-related mood disorders. Biological Psychiatry, 59, 11161127.CrossRefGoogle ScholarPubMed
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257269.CrossRefGoogle ScholarPubMed
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans–Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23, 728.CrossRefGoogle Scholar
Essex, M. J., Boyce, W. T., Hertzman, C., Lam, L. L., Armstrong, J. M., Neumann, S. M. et al. (2013). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Development, 84, 5875.CrossRefGoogle ScholarPubMed
Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry, 164, 14761488.CrossRefGoogle ScholarPubMed
Feil, R., & Fraga, M. F. (2011). Epigenetics and the environment: Emerging patterns and implications. Nature Reviews, Genetics, 13, 97109.CrossRefGoogle Scholar
Field, T., Diego, M., Hernandez-Reif, M., Schanberg, S., Kuhn, C., Yando, R., et al. (2003). Pregnancy anxiety and comorbid depression and anger: Effects on the fetus and neonate. Depression and Anxiety, 17, 140151.CrossRefGoogle ScholarPubMed
Filiberto, A. C., Maccani, M. A., Koestler, D., Wilhelm-Benartzi, C., Avissar-Whiting, M., Banister, C. E., et al. (2011). Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta. Epigenetics, 6, 566572.CrossRefGoogle ScholarPubMed
Gatt, J. M., Nemeroff, C. B., Dobson-Stone, C., Paul, R. H., Bryant, R. A., Schofield, P. R., et al. (2009). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry, 14, 681695.CrossRefGoogle ScholarPubMed
Grant, K. A., McMahon, C., & Austin, M. P. (2008). Maternal anxiety during the transition to parenthood: A prospective study. Journal of Affective Disorders, 108, 101111.CrossRefGoogle ScholarPubMed
Groves, J. O. (2007). Is it time to reassess the BDNF hypothesis of depression? Molecular Psychiatry, 12, 10791088.CrossRefGoogle Scholar
Gunnar, M. R., Wenner, J. A., Thomas, K. M., Glatt, C. E., McKenna, M. C., & Clark, A. G. (2012). The brain-derived neurotrophic factor Val66Met polymorphism moderates early deprivation effects on attention problems. Development and Psychopathology, 24, 12151223.CrossRefGoogle ScholarPubMed
Hajcak, G., Castille, C., Olvet, D. M., Dunning, J. P., Roohi, J., & Hatchwell, E. (2009). Genetic variation in brain-derived neurotrophic factor and human fear conditioning. Genes, Brain, and Behavior, 8, 8085.CrossRefGoogle ScholarPubMed
Hariri, A. R., Goldberg, T. E., Mattay, V. S., Kolachana, B. S., Callicott, J. H., Egan, M. F., et al. (2003). Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. Journal of Neuroscience, 23, 66906694.CrossRefGoogle ScholarPubMed
Hayden, E. P., Klein, D. N., Dougherty, L. R., Olino, T. M., Dyson, M. W., Durbin, C. E., et al. (2010). The role of brain-derived neurotrophic factor genotype, parental depression, and relationship discord in predicting early-emerging negative emotionality. Psychological Science, 21, 16781685.CrossRefGoogle ScholarPubMed
Heim, C., & Binder, E. B. (2012). Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene–environment interactions, and epigenetics. Experimental Neurology, 233, 102111.CrossRefGoogle ScholarPubMed
Heim, C., & Nemeroff, C. B. (2009). Neurobiology of posttraumatic stress disorder. CNS Spectrums, 14(Suppl. 1), 1324.Google ScholarPubMed
Hettema, J. M., Neale, M. C., & Kendler, K. S. (2001). A review and meta-analysis of the genetic epidemiology of anxiety disorders. American Journal of Psychiatry, 158, 15681578.CrossRefGoogle ScholarPubMed
Hilt, L. M., Sander, L. C., Nolen-Hoeksema, S., & Simen, A. A. (2007). The BDNF Val66Met polymorphism predicts rumination and depression differently in young adolescent girls and their mothers. Neuroscience Letters, 429, 1216.CrossRefGoogle ScholarPubMed
Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., et al. (2013). Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research, 47, 880891.CrossRefGoogle ScholarPubMed
Huizink, A. C., de Medina, P. G., Mulder, E. J., Visser, G. H., & Buitelaar, J. K. (2002). Psychological measures of prenatal stress as predictors of infant temperament. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 10781085.CrossRefGoogle ScholarPubMed
Hunnerkopf, R., Strobel, A., Gutknecht, L., Brocke, B., & Lesch, K. P. (2007). Interaction between BDNF Val66Met and dopamine transporter gene variation influences anxiety-related traits. Neuropsychopharmacology, 32, 25522560.CrossRefGoogle ScholarPubMed
Jiang, L., Willner, D., Danoy, P., Xu, H., & Brown, M. A. (2013). Comparison of the performance of two commercial genome-wide association study genotyping platforms in Han Chinese samples. G3 (Bethesda, Md.), 3, 2329.CrossRefGoogle ScholarPubMed
Jiang, X., Xu, K., Hoberman, J., Tian, F., Marko, A. J., Waheed, J. F., et al. (2005). BDNF variation and mood disorders: A novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects. Neuropsychopharmacology, 30, 13531361.CrossRefGoogle ScholarPubMed
Jirtle, R. L., & Skinner, M. K. (2007). Environmental epigenomics and disease susceptibility. Nature Reviews Genetics, 8, 253262.CrossRefGoogle ScholarPubMed
Johnson, W. E., Li, C., & Rabinovic, A. (2007). Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics, 8, 118127.CrossRefGoogle ScholarPubMed
Juhasz, G., Foldi, I., & Penke, B. (2011). Systems biology of Alzheimer's disease: How diverse molecular changes result in memory impairment in AD. Neurochemistry International, 58, 739750.CrossRefGoogle ScholarPubMed
Kim, C. H., Cheon, K. A., Koo, M. S., Ryu, Y. H., Lee, J. D., Chang, J. W., et al. (2007). Dopamine transporter density in the basal ganglia in obsessive–compulsive disorder, measured with [123I]IPT SPECT before and after treatment with serotonin reuptake inhibitors. Neuropsychobiology, 55, 156162.CrossRefGoogle ScholarPubMed
Kleim, J. A., Chan, S., Pringle, E., Schallert, K., Procaccio, V., Jimenez, R., et al. (2006). BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nature Neuroscience, 9, 735737.CrossRefGoogle ScholarPubMed
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., et al. (2013). Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions. Nature Neuroscience, 16, 3341.CrossRefGoogle ScholarPubMed
Krishnan, V., Han, M. H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., et al. (2007). Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell, 131, 391404.CrossRefGoogle ScholarPubMed
Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., et al. (2012). Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry, 72, 4148.CrossRefGoogle Scholar
Lau, J. Y., Goldman, D., Buzas, B., Hodgkinson, C., Leibenluft, E., Nelson, E., et al. (2010). BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents. NeuroImage, 53, 952961.CrossRefGoogle ScholarPubMed
Lonsdorf, T. B., Weike, A. I., Golkar, A., Schalling, M., Hamm, A. O., & Ohman, A. (2010). Amygdala-dependent fear conditioning in humans is modulated by the BDNF val66met polymorphism. Behavioral Neuroscience, 124, 915.CrossRefGoogle Scholar
Martinowich, K., & Lu, B. (2008). Interaction between BDNF and serotonin: Role in mood disorders. Neuropsychopharmacology, 33, 7383.CrossRefGoogle ScholarPubMed
Mata, J., Thompson, R. J., & Gotlib, I. H. (2010). BDNF genotype moderates the relation between physical activity and depressive symptoms. Health Psychology, 29, 130133.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, 342348.CrossRefGoogle ScholarPubMed
McHughen, S. A., Rodriguez, P. F., Kleim, J. A., Kleim, E. D., Marchal Crespo, L., Procaccio, V., et al. (2010). BDNF val66met polymorphism influences motor system function in the human brain. Cerebral Cortex, 20, 12541262.CrossRefGoogle ScholarPubMed
Meaney, M. J., & Ferguson-Smith, A. C. (2010). Epigenetic regulation of the neural transcriptome: The meaning of the marks. Nature Neuroscience, 13, 13131318.CrossRefGoogle ScholarPubMed
Meaney, M. J., LeDoux, J. E., & Leibowitz, M. L. (2008). Neurobiology of anxiety disorders. In Tasman, A., Kay, J., Lieberman, J. A., First, M. B., & Maj, M. (Eds.), Psychiatry (Vol. 1, 3rd ed., pp. 317338). Chichester: Wiley.CrossRefGoogle Scholar
Mennes, M., Stiers, P., Lagae, L., & Van den Bergh, B. (2006). Long-term cognitive sequelae of antenatal maternal anxiety: Involvement of the orbitofrontal cortex. Neuroscience & Biobehavioral Reviews, 30, 10781086.CrossRefGoogle ScholarPubMed
Montag, C., Basten, U., Stelzel, C., Fiebach, C. J., & Reuter, M. (2010). The BDNF Val66Met polymorphism and anxiety: Support for animal knock-in studies from a genetic association study in humans. Psychiatry Research, 179, 8690.CrossRefGoogle ScholarPubMed
Montag, C., Reuter, M., Newport, B., Elger, C., & Weber, B. (2008). The BDNF Val66Met polymorphism affects amygdala activity in response to emotional stimuli: Evidence from a genetic imaging study. NeuroImage, 42, 15541559.CrossRefGoogle ScholarPubMed
Mulligan, C., D'Errico, N., Stees, J., & Hughes, D. (2012). Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics, 7, 853857.CrossRefGoogle ScholarPubMed
Murray, L., Creswell, C., & Cooper, P. J. (2009). The development of anxiety disorders in childhood: An integrative review. Psychological Medicine, 39, 14131423.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, 97106.CrossRefGoogle ScholarPubMed
Ong, M. L., & Holbrook, J. D. (2013). Novel region discovery method for Infinium 450 K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways. Aging Cell, 13, 142155.CrossRefGoogle Scholar
Pan, H., Chen, L., Dogra, S., Ling Teh, A., Tan, J. H., Lim, Y. I., et al. (2012). Measuring the methylome in clinical samples: Improved processing of the Infinium Human Methylation450 BeadChip Array. Epigenetics, 7, 11731187.CrossRefGoogle ScholarPubMed
Paulus, M. P., Rogalsky, C., Simmons, A., Feinstein, J. S., & Stein, M. B. (2003). Increased activation in the right insula during risk-taking decision making is related to harm avoidance and neuroticism. NeuroImage, 19, 14391448.CrossRefGoogle ScholarPubMed
Perroud, N., Dayer, A., Piguet, C., Nallet, A., Favre, S., Malafosse, A., et al. (2014). Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder. British Journal of Psychiatry, 204, 3035.CrossRefGoogle ScholarPubMed
Perroud, N., Paoloni–Giacobino, A., Prada, P., Olie, E., Salzmann, A., Nicastro, R., et al. (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.CrossRefGoogle ScholarPubMed
Petryshen, T. L., Sabeti, P. C., Aldinger, K. A., Fry, B., Fan, J. B., Schaffner, S. F., et al. (2010). Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Molecular Psychiatry, 15, 810815.CrossRefGoogle ScholarPubMed
Pluess, M., & Belsky, J. (2011). Prenatal programming of postnatal plasticity? Development and Psychopathology, 23, 2938.CrossRefGoogle ScholarPubMed
Pluess, M., Velders, F. P., Belsky, J., van IJzendoorn, M. H., Bakermans–Kranenburg, M. J., Jaddoe, V. W., et al. (2011). Serotonin transporter polymorphism moderates effects of prenatal maternal anxiety on infant negative emotionality. Biological Psychiatry, 69, 520525.CrossRefGoogle ScholarPubMed
Qiu, A., Rifkin-Graboi, A., Chen, H., Chong, Y. S., Kwek, K., Gluckman, P. D., et al. (2013). Maternal anxiety and infants' hippocampal development: Timing matters. Translational Psychiatry, 3, e306.CrossRefGoogle ScholarPubMed
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., Meyer, A., et al. (2011). Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Translational Psychiatry, 1, e21.CrossRefGoogle ScholarPubMed
Rakyan, V. K., Down, T. A., Balding, D. J., & Beck, S. (2011). Epigenome-wide association studies for common human diseases. Nature Reviews Genetics, 12, 529541.CrossRefGoogle ScholarPubMed
Rauch, S. L., Savage, C. R., Alpert, N. M., Fischman, A. J., & Jenike, M. A. (1997). The functional neuroanatomy of anxiety: A study of three disorders using positron emission tomography and symptom provocation. Biological Psychiatry, 42, 446452.CrossRefGoogle ScholarPubMed
Rifkin-Graboi, A., Bai, J., Chen, H., Hameed, W. B., Sim, L. W., Tint, M. T., et al. (2013). Prenatal maternal depression associates with microstructure of right amygdala in neonates at birth. Biological Psychiatry, 74, 837844.CrossRefGoogle ScholarPubMed
Risbrough, V. B., & Stein, M. B. (2006). Role of corticotropin releasing factor in anxiety disorders: A translational research perspective. Hormones and Behavior, 50, 550561.CrossRefGoogle ScholarPubMed
Rosenbaum, J. F., Biederman, J., Bolduc-Murphy, E. A., Faraone, S. V., Chaloff, J., Hirshfeld, D. R., et al. (1993). Behavioral inhibition in childhood: A risk factor for anxiety disorders. Harvard Review of Psychiatry, 1, 216.CrossRefGoogle ScholarPubMed
Roth, T. L., & Sweatt, J. D. (2011). Annual Research Review: Epigenetic mechanisms and environmental shaping of the brain during sensitive periods of development. Journal of Child Psychology and Psychiatry, 52, 398408.CrossRefGoogle ScholarPubMed
Rutter, M., Moffitt, T. E., & Caspi, A. (2006). Gene–environment interplay and psychopathology: Multiple varieties but real effects. Journal of Child Psychology and Psychiatry, 47, 226261.CrossRefGoogle ScholarPubMed
Rybakowski, J. K. (2008). BDNF gene: Functional Val66Met polymorphism in mood disorders and schizophrenia. Pharmacogenomics, 9, 15891593.CrossRefGoogle Scholar
Schroeder, J. W., Smith, A. K., Brennan, P. A., Conneely, K. N., Kilaru, V., Knight, B. T., et al. (2012). DNA methylation in neonates born to women receiving psychiatric care. Epigenetics, 7, 409414.CrossRefGoogle ScholarPubMed
Shalev, I., Lerer, E., Israel, S., Uzefovsky, F., Gritsenko, I., Mankuta, D., et al. (2009). BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions. Psychoneuroendocrinology, 34, 382388.CrossRefGoogle ScholarPubMed
Soh, S. E., Tint, M. T., Gluckman, P. D., Godfrey, K. M., Rifkin-Graboi, A., Chan, Y. H., et al. (2013). Cohort profile: Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. International Journal of Epidemiology, 43, 14011409.CrossRefGoogle ScholarPubMed
Spielberger, C. D., Gorsuch, R. L., & Lushene, R. E. (1970). Manual for the State–Trait Anxiety Inventory. Retrieved from https://ubir.buffalo.edu/xmlui/handle/10477/2895Google Scholar
Staufenbiel, S. M., Penninx, B. W., Spijker, A. T., Elzinga, B. M., & van Rossum, E. F. (2013). Hair cortisol, stress exposure, and mental health in humans: A systematic review. Psychoneuroendocrinology, 38, 12201235.CrossRefGoogle ScholarPubMed
Steiger, H., Labonte, B., Groleau, P., Turecki, G., & Israel, M. (2013). Methylation of the glucocorticoid receptor gene promoter in bulimic women: Associations with borderline personality disorder, suicidality, and exposure to childhood abuse. International Journal of Eating Disorder, 46, 246255.CrossRefGoogle ScholarPubMed
Stein, M. B., Simmons, A. N., Feinstein, J. S., & Paulus, M. P. (2007). Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. American Journal of Psychiatry, 164, 318327.CrossRefGoogle ScholarPubMed
Suzuki, A., Matsumoto, Y., Shibuya, N., Ryoichi, S., Kamata, M., Enokido, M., et al. (2012). Interaction effect between the BDNF Val66Met polymorphism and parental rearing for interpersonal sensitivity in healthy subjects. Psychiatry Research, 200, 945948.CrossRefGoogle ScholarPubMed
Taylor, R. C., Sanfilippo, A., McDermott, J. E., Baddeley, B., Riensche, R., Jensen, R., et al. (2010). Enriching regulatory networks by bootstrap learning using optimised GO-based gene similarity and gene links mined from PubMed abstracts. International Journal of Computational Biology and Drug Design, 4, 5682.CrossRefGoogle Scholar
Teh, A. L., Pan, H., Chen, L., Ong, M. L., Dogra, S., Wong, J., et al. (2014). The effect of genotype and in utero environment on inter-individual variation in neonate DNA methylomes. Genome Research, 24, 10641074.CrossRefGoogle Scholar
Teixeira, J. M., Fisk, N. M., & Glover, V. (1999). Association between maternal anxiety in pregnancy and increased uterine artery resistance index: Cohort based study. British Medical Journal, 318, 153157.CrossRefGoogle Scholar
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
Uher, R., & McGuffin, P. (2008). The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: Review and methodological analysis. Molecular Psychiatry, 13, 131146.CrossRefGoogle ScholarPubMed
Van den Bergh, B. R., Mulder, E. J., Mennes, M., & Glover, V. (2005). Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: Links and possible mechanisms. A review. Neuroscience & Biobehavioral Reviews, 29, 237258.CrossRefGoogle ScholarPubMed
Wagner, S., Baskaya, O., Dahmen, N., Lieb, K., & Tadic, A. (2010). Modulatory role of the brain-derived neurotrophic factor Val66Met polymorphism on the effects of serious life events on impulsive aggression in borderline personality disorder. Genes, Brain, and Behavior, 9, 97102.CrossRefGoogle ScholarPubMed
Wang, C., Zhang, Y., Liu, B., Long, H., Yu, C., & Jiang, T. (2014). Dosage effects of BDNF Val66Met polymorphism on cortical surface area and functional connectivity. Journal of Neuroscience, 34, 26452651.CrossRefGoogle ScholarPubMed
Weinstock, M. (1997). Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis? Neuroscience & Biobehavioral Reviews, 21, 110.CrossRefGoogle ScholarPubMed
Wendland, J. R., Kruse, M. R., Cromer, K. R., & Murphy, D. L. (2007). A large case-control study of common functional SLC6A4 and BDNF variants in obsessive-compulsive disorder. Neuropsychopharmacology, 32, 25432551.CrossRefGoogle Scholar
Wichers, M., Kenis, G., Jacobs, N., Mengelers, R., Derom, C., Vlietinck, R., et al. (2008). The BDNF Val(66)Met × 5-HTTLPR × Child Adversity interaction and depressive symptoms: An attempt at replication. American Journal of Medical Genetics, 147B, 120123.CrossRefGoogle ScholarPubMed
Willoughby, M. T., Mills-Koonce, R., Propper, C. B., & Waschbusch, D. A. (2013). Observed parenting behaviors interact with a polymorphism of the brain-derived neurotrophic factor gene to predict the emergence of oppositional defiant and callous–unemotional behaviors at age 3 years. Development and Psychopatholoy, 25, 903917.CrossRefGoogle ScholarPubMed
Wright, C. I., Martis, B., McMullin, K., Shin, L. M., & Rauch, S. L. (2003). Amygdala and insular responses to emotionally valenced human faces in small animal specific phobia. Biological Psychiatry, 54, 10671076.CrossRefGoogle ScholarPubMed
Xie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Farrer, L. A., et al. (2010). Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology, 35, 16841692.CrossRefGoogle ScholarPubMed
Zhang, T. Y., & Meaney, M. J. (2010) Epigenetics and the environmental regulation of the genome and its function. Annual Reviews of Psychology, 61, 439466.CrossRefGoogle ScholarPubMed
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Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes
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Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes
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