Association of childhood chronic physical aggression with a DNA methylation signature in adult human T cells

PLoS ONE

Volumn 9, Issue 4, 2014, Pages

  Provençal, Nadine ^a,b   Suderman, Matthew J ^a,e   Guillemin, Claire ^a,b   Vitaro, Frank ^b,c   Côté, Sylvana M ^b,c   Hallett, Michael ^e   Tremblay, Richard E ^b,c,d   Szyf, Moshe ^a  

^a MCGILL UNIVERSITY   (Canada)

^b UNIVERSITY OF MONTREAL   (Canada)

^c UNIVERSITÉ DE MONTRÉAL   (Canada)

^d UNIVERSITY COLLEGE DUBLIN   (Ireland)

^e MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; MICRORNA;

ADOLESCENT; AGGRESSION; ARTICLE; AVPR1A GENE; CHILD; CHRONIC PHYSICAL AGGRESSION; CONTROLLED STUDY; DNA METHYLATION; DRD1 GENE; GENE; GENE CLUSTER; GENETIC ASSOCIATION; GENOME; GRM5 GENE; HTR1D GENE; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; HYBRIDIZATION; MALE; MICROARRAY ANALYSIS; NUCLEOTIDE SEQUENCE; PROMOTER REGION; SLC6A3 GENE; T LYMPHOCYTE; ADULT; CASE CONTROL STUDY; CLUSTER ANALYSIS; CPG ISLAND; FEMALE; GENETICS; HUMAN CHROMOSOME; HUMAN GENOME; METABOLISM; PHYSIOLOGY;

ADULT; AGGRESSION; CASE-CONTROL STUDIES; CHILD; CHROMOSOMES, HUMAN; CLUSTER ANALYSIS; CPG ISLANDS; DNA METHYLATION; FEMALE; GENOME, HUMAN; HUMANS; MALE; PROMOTER REGIONS, GENETIC; T-LYMPHOCYTES;

EID: 84898898916     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0089839     Document Type: Article

References (107)

1. NICHD Early Child Care Research Network (2004) Trajectories of physical aggression from toddlerhood to middle childhood: predictors, correlates, and outcomes. Monogr Soc Res Child Dev 69: vii, 1-129.
2. Alink LR, Mesman J, van Zeijl J, Stolk MN, Juffer F, et al. (2006) The early childhood aggression curve: development of physical aggression in 10- to 50-month-old children. Child Dev 77: 954-966. (Pubitemid 44117905)
3. Cote SM, Vaillancourt T, LeBlanc JC, Nagin DS, Tremblay RE (2006) The development of physical aggression from toddlerhood to pre-adolescence: a nation wide longitudinal study of Canadian children. J Abnorm Child Psychol 34: 71-85. (Pubitemid 43800465)
4. Tremblay RE (2010) Developmental origins of disruptive behaviour problems: the 'original sin' hypothesis, epigenetics and their consequences for prevention. J Child Psychol Psychiatry 51: 341-367.
5. Broidy LM, Nagin DS, Tremblay RE, Bates JE, Brame B, et al. (2003) Developmental trajectories of childhood disruptive behaviors and adolescent delinquency: a six-site, cross-national study. Dev Psychol 39: 222-245. (Pubitemid 37189423)
6. Campbell SB, Spieker S, Burchinal M, Poe MD (2006) Trajectories of aggression from toddlerhood to age 9 predict academic and social functioning through age 12. J Child Psychol Psychiatry 47: 791-800. (Pubitemid 44101359)
7. Campbell SB, Spieker S, Vandergrift N, Belsky J, Burchinal M (2010) Predictors and sequelae of trajectories of physical aggression in school-age boys and girls. Dev Psychopathol 22: 133-150.
8. Cote SM, Boivin M, Nagin DS, Japel C, Xu Q, et al. (2007) The role of maternal education and nonmaternal care services in the prevention of children's physical aggression problems. Arch Gen Psychiatry 64: 1305-1312. (Pubitemid 350074828)
9. Nagin DS, Tremblay RE (2001) Parental and early childhood predictors of persistent physical aggression in boys from kindergarten to high school. Arch Gen Psychiatry 58: 389-394. (Pubitemid 32299535)
10. Barker ED, Seguin JR, White HR, Bates ME, Lacourse E, et al. (2007) Developmental trajectories of male physical violence and theft: relations to neurocognitive performance. Arch Gen Psychiatry 64: 592-599. (Pubitemid 46718292)
11. Barker ED, Boivin M, Brendgen M, Fontaine N, Arseneault L, et al. (2008) Predictive validity and early predictors of peer-victimization trajectories in preschool. Arch Gen Psychiatry 65: 1185-1192.
12. Nagin D, Tremblay RE (1999) Trajectories of boys' physical aggression, opposition, and hyperactivity on the path to physically violent and nonviolent juvenile delinquency. Child Dev 70: 1181-1196.
13. Seguin JR, Boulerice B, Harden PW, Tremblay RE, Pihl RO (1999) Executive functions and physical aggression after controlling for attention deficit hyperactivity disorder, general memory, and IQ. J Child Psychol Psychiatry 40: 1197-1208.
14. Kokko K, Pulkkinen L, Huesmann LR, Dubow EF, Boxer P (2009) Intensity of Aggression in Childhood as a Predictor of Different Forms of Adult Aggression: A Two-Country (Finland and United States) Analysis. J Res Adolesc 19: 9-34.
15. Bennett AJ, Lesch KP, Heils A, Long JC, Lorenz JG, et al. (2002) Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7: 118-122. (Pubitemid 34087891)
16. Brendgen M, Boivin M, Vitaro F, Bukowski WM, Dionne G, et al. (2008) Linkages between children's and their friends' social and physical aggression: evidence for a gene-environment interaction? Child Dev 79: 13-29.
17. Dionne G, Tremblay R, Boivin M, Laplante D, Perusse D (2003) Physical aggression and expressive vocabulary in 19-month-old twins. Dev Psychol 39: 261-273. (Pubitemid 37189425)
18. Hicks BM, Krueger RF, Iacono WG, McGue M, Patrick CJ (2004) Family transmission and heritability of externalizing disorders: a twin-family study. Arch Gen Psychiatry 61: 922-928. (Pubitemid 39181082)
19. van Lier PA, van der Ende J, Koot HM, Verhulst FC (2007) Which better predicts conduct problems? The relationship of trajectories of conduct problems with ODD and ADHD symptoms from childhood into adolescence. J Child Psychol Psychiatry 48: 601-608. (Pubitemid 46902330)
20. Pavlov KA, Chistiakov DA, Chekhonin VP (2011) Genetic determinants of aggression and impulsivity in humans. J Appl Genet.
21. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, et al. (2002) Role of genotype in the cycle of violence in maltreated children. Science 297: 851-854. (Pubitemid 34839638)
22. Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, et al. (2006) MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis. Mol Psychiatry 11: 903-913. (Pubitemid 44470213)
23. Tremblay RE, Szyf M (2010) Developmental origins of chronic physical aggression and epigenetics. Epigenomics 2: 495-499.
24. Razin A (1998) CpG methylation, chromatin structure and gene silencing-a three-way connection. EMBO J 17: 4905-4908.
25. Szyf M (2011) The early life social environment and DNA methylation: DNA methylation mediating the long-term impact of social environments early in life. Epigenetics 6: 971-978.
26. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23: 5293-5300. (Pubitemid 36950884)
27. Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL (2006) Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 114: 567-572.
28. Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8: 253-262. (Pubitemid 46439287)
29. MacLennan NK, James SJ, Melnyk S, Piroozi A, Jernigan S, et al. (2004) Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genomics 18: 43-50. (Pubitemid 39319485)
30. Ke X, Lei Q, James SJ, Kelleher SL, Melnyk S, et al. (2006) Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics 25: 16-28.
31. Weaver IC, Diorio J, Seckl JR, Szyf M, Meaney MJ (2004) Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites. Ann N Y Acad Sci 1024: 182-212. (Pubitemid 38879602)
32. Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, et al. (2007) DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A 104: 19351-19356.
33. McGowan PO, Suderman M, Sasaki A, Huang TC, Hallett M, et al. (2011) Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One 6: e14739.
34. Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmuhl Y, et al. (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 12: 1559-1566.
35. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, et al. (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105: 17046-17049.
36. Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, et al. (2008) Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3: 97-106.
37. McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonte B, et al. (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12: 342-348.
38. Razin A, Szyf M (1984) DNA methylation patterns. Formation and function. Biochim Biophys Acta 782: 331-342. (Pubitemid 14038241)
39. Kinnally EL, Feinberg C, Kim D, Ferguson K, Leibel R, et al. (2011) DNA methylation as a risk factor in the effects of early life stress. Brain Behav Immun.
40. Uddin M, Aiello AE, Wildman DE, Koenen KC, Pawelec G, et al. (2011) Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proc Natl Acad Sci U S A 107: 9470-9475.
41. Uddin M, Koenen KC, Aiello AE, Wildman DE, de los Santos R, et al. (2011) Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample. Psychol Med 41: 997-1007.
42. Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, et al. (2011) Differential immune system DNA methylation and cytokine regulation in posttraumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 156B: 700-708.
43. Borghol N, Suderman M, McArdle W, Racine A, Hallett M, et al. (2012) Associations with early-life socio-economic position in adult DNA methylation. Int J Epidemiol 41: 62-74.
44. Ressler KJ, Mercer KB, Bradley B, Jovanovic T, Mahan A, et al. (2011) Posttraumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 470: 492-497.
45. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, et al. (2013) Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 16: 33-41.
46. Wang D, Szyf M, Benkelfat C, Provencal N, Turecki G, et al. (2012) Peripheral SLC6A4 DNA Methylation Is Associated with In Vivo Measures of Human Brain Serotonin Synthesis and Childhood Physical Aggression. PLoS One 7: e39501.
47. Provencal N, Suderman MJ, Caramaschi D, Wang D, Hallett M, et al. (2013) Differential DNA methylation regions in cytokine and transcription factor genomic Loci associate with childhood physical aggression. PLoS One 8: e71691.
48. Provencal N, Suderman MJ, Vitaro F, Szyf M, Tremblay RE (2013) Childhood chronic physical aggression associates with adult cytokine levels in plasma. PLoS One 8: e69481.
49. Pingault JB, Tremblay RE, Vitaro F, Carbonneau R, Genolini C, et al. (2011) Childhood Trajectories of Inattention and Hyperactivity and Prediction of Educational Attainment in Early Adulthood: A 16-Year Longitudinal Population-Based Study. Am J Psychiatry.
50. Smyth GK (2005) Limma: linear models for microarray data. In: R. . Gentleman VC, S. Dudoit, R. Irizarry, W. Huber editor. Bioinformatics and Computational Biology Solutions using R and Bioconductor. New York: Springer, pp. 397-420.
51. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.
52. Ngwa JS, Manning AK, Grimsby JL, Lu C, Zhuang WV, et al. (2011) Pathway analysis following association study. BMC Proc 5 Suppl 9: S18.
53. Down TA, Rakyan VK, Turner DJ, Flicek P, Li H, et al. (2008) A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nat Biotechnol 26: 779-785. (Pubitemid 351961453)
54. Bell CG, Finer S, Lindgren CM, Wilson GA, Rakyan VK, et al. (2010) Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus. PLoS One 5: e14040.
55. Cheung HH, Lee TL, Davis AJ, Taft DH, Rennert OM, et al. (2010) Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer. Br J Cancer 102: 419-427.
56. Flanagan JM, Cocciardi S, Waddell N, Johnstone CN, Marsh A, et al. (2010) DNA methylome of familial breast cancer identifies distinct profiles defined by mutation status. Am J Hum Genet 86: 420-433.
57. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK (2010) Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One 5.
58. Gunther T, Grundhoff A (2010) The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes. PLoS Pathog 6: e1000935.
59. Hiura H, Sugawara A, Ogawa H, John RM, Miyauchi N, et al. (2010) A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. Nucleic Acids Res 38: 4929-4945.
60. Lempiainen H, Muller A, Brasa S, Teo SS, Roloff TC, et al. (2011) Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice. PLoS One 6: e18216.
61. Morris MR, Ricketts CJ, Gentle D, McRonald F, Carli N, et al. (2011) Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene 30: 1390-1401.
62. Movassagh M, Choy MK, Goddard M, Bennett MR, Down TA, et al. (2010) Differential DNA methylation correlates with differential expression of angiogenic factors in human heart failure. PLoS One 5: e8564.
63. Tsui DW, Lam YM, Lee WS, Leung TY, Lau TK, et al. (2010) Systematic identification of placental epigenetic signatures for the noninvasive prenatal detection of Edwards syndrome. PLoS One 5: e15069.
64. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, et al. (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37: 853-862. (Pubitemid 41077111)
65. Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, et al. (2006) Evidence for an instructive mechanism of de novo methylation in cancer cells. Nat Genet 38: 149-153. (Pubitemid 43177227)
66. Novak JP, Kim SY, Xu J, Modlich O, Volsky DJ, et al. (2006) Generalization of DNA microarray dispersion properties: microarray equivalent of t-distribution. Biol Direct 1: 27.
67. Zhang S (2006) An improved nonparametric approach for detecting differentially expressed genes with replicated microarray data. Stat Appl Genet Mol Biol 5: Article30.
68. Cheng AS, Culhane AC, Chan MW, Venkataramu CR, Ehrich M, et al. (2008) Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome. Cancer Res 68: 1786-1796. (Pubitemid 351416564)
69. Tomazou EM, Rakyan VK, Lefebvre G, Andrews R, Ellis P, et al. (2008) Generation of a genomic tiling array of the human major histocompatibility complex (MHC) and its application for DNA methylation analysis. BMC Med Genomics 1: 19.
70. Liu Y, Balaraman Y, Wang G, Nephew KP, Zhou FC (2009) Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics 4: 500-511.
71. Murphy DM, Buckley PG, Bryan K, Das S, Alcock L, et al. (2009) Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation. PLoS One 4: e8154.
72. Takeshima H, Yamashita S, Shimazu T, Niwa T, Ushijima T (2009) The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands. Genome Res 19: 1974-1982.
73. Feber A, Wilson GA, Zhang L, Presneau N, Idowu B, et al. (2011) Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome Res 21: 515-524.
74. Jia J, Pekowska A, Jaeger S, Benoukraf T, Ferrier P, et al. (2010) Assessing the efficiency and significance of Methylated DNA Immunoprecipitation (MeDIP) assays in using in vitro methylated genomic DNA. BMC Res Notes 3: 240.
75. Jin SG, Kadam S, Pfeifer GP (2010) Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res 38: e125.
76. Nair SS, Coolen MW, Stirzaker C, Song JZ, Statham AL, et al. (2011) Comparison of methyl-DNA immunoprecipitation (MeDIP) and methyl-CpG binding domain (MBD) protein capture for genome-wide DNA methylation analysis reveal CpG sequence coverage bias. Epigenetics 6: 34-44.
77. Rajendram R, Ferreira JC, Grafodatskaya D, Choufani S, Chiang T, et al. (2011) Assessment of methylation level prediction accuracy in methyl-DNA immunoprecipitation and sodium bisulfite based microarray platforms. Epigenetics 6: 410-415.
78. Robinson MD, Stirzaker C, Statham AL, Coolen MW, Song JZ, et al. (2010) Evaluation of affinity-based genome-wide DNA methylation data: effects of CpG density, amplification bias, and copy number variation. Genome Res 20: 1719-1729.
79. Yang L, Zhang K, Dai W, He X, Zhao Q, et al. (2011) Systematic evaluation of genome-wide methylated DNA enrichment using a CpG island array. BMC Genomics 12: 10.
80. Irizarry RA, Ladd-Acosta C, Carvalho B, Wu H, Brandenburg SA, et al. (2008) Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res 18: 780-790. (Pubitemid 351645068)
81. Yukawa K, Iso H, Tanaka T, Tsubota Y, Owada-Makabe K, et al. (2005) Down-regulation of dopamine transporter and abnormal behavior in STAT6-deficient mice. Int J Mol Med 15: 819-825.
82. Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321: 209-213.
83. Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196: 261-282. (Pubitemid 17122132)
84. Rossi RL, Rossetti G, Wenandy L, Curti S, Ripamonti A, et al. (2011) Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b. Nat Immunol 12: 796-803.
85. Borghol N, Lornage J, Blachere T, Sophie Garret A, Lefevre A (2006) Epigenetic status of the H19 locus in human oocytes following in vitro maturation. Genomics 87: 417-426. (Pubitemid 43214514)
86. Tsai KW, Kao HW, Chen HC, Chen SJ, Lin WC (2009) Epigenetic control of the expression of a primate-specific microRNA cluster in human cancer cells. Epigenetics 4: 587-592.
87. Ferris CF, Lu SF, Messenger T, Guillon CD, Heindel N, et al. (2006) Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior. Pharmacol Biochem Behav 83: 169-174.
88. Ferris CF (2005) Vasopressin/oxytocin and aggression. Novartis Found Symp 268: 190-198; discussion 198-200, 242-153.
89. de Almeida RM, Ferrari PF, Parmigiani S, Miczek KA (2005) Escalated aggressive behavior: dopamine, serotonin and GABA. Eur J Pharmacol 526: 51-64. (Pubitemid 41744105)
90. Sweet RA, Nimgaonkar VL, Kamboh MI, Lopez OL, Zhang F, et al. (1998) Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer disease. Arch Neurol 55: 1335-1340. (Pubitemid 28465867)
91. Guo G, Roettger ME, Shih JC (2007) Contributions of the DAT1 and DRD2 genes to serious and violent delinquency among adolescents and young adults. Hum Genet 121: 125-136. (Pubitemid 46421149)
92. Vaughn M, DeLisi M, Beaver K, Wright J (2009) DAT1 and 5HTT are associated with pathological criminal behavior in a nationally representative sample of youth. Crim Justice Behav 36: 1113-1124.
93. Navarro JF, Postigo D, Martin M, Buron E (2006) Antiaggressive effects of MPEP, a selective antagonist of mGlu5 receptors, in agonistic interactions between male mice. Eur J Pharmacol 551: 67-70. (Pubitemid 44648050)
94. Miczek KA, Fish EW (2005) Monoamines, GABA, Glutamate, and Aggression. In: Nelson RJ, editor. Biology of Aggression: Oxford University Press.
95. Takahashi A, Quadros IM, de Almeida RM, Miczek KA (2012) Behavioral and Pharmacogenetics of Aggressive Behavior. Curr Top Behav Neurosci.
96. Vage J, Wade C, Biagi T, Fatjo J, Amat M, et al. (2010) Association of dopamine- and serotonin-related genes with canine aggression. Genes Brain Behav 9: 372-378.
97. Berlivet S, Moussette S, Ouimet M, Verlaan DJ, Koka V, et al. (2012) Interaction between genetic and epigenetic variation defines gene expression patterns at the asthma-associated locus 17q12-q21 in lymphoblastoid cell lines. Hum Genet.
98. Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS (2011) Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association. Neuromolecular Med 13: 66-76.
99. van IMH, Caspers K, Bakermans-Kranenburg MJ, Beach SR, Philibert R (2010) Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma. Biol Psychiatry 68: 405-407.
100. David S, Meltzer SJ (2011) Stomach - Genetic and epigenetic alterations of preneoplastic and neoplastic lesions. Cancer Biomark 9: 493-507.
101. Provençal N, Suderman JM, Guillemin C, Massart R, Ruggiero A, et al. (2012) The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells. J Neurosci.
102. Nelson RJ, Chiavegatto S (2001) Molecular basis of aggression. Trends Neurosci 24: 713-719. (Pubitemid 33097538)
103. Siegel A, Bhatt S, Bhatt R, Zalcman SS (2007) The neurobiological bases for development of pharmacological treatments of aggressive disorders. Curr Neuropharmacol 5: 135-147. (Pubitemid 47019427)
104. Zalcman SS, Siegel A (2006) The neurobiology of aggression and rage: role of cytokines. Brain Behav Immun 20: 507-514. (Pubitemid 44528957)
105. Alleva E, Cirulli F, Bianchi M, Bondiolotti GP, Chiarotti F, et al. (1998) Behavioural characterization of interleukin-6 overexpressing or deficient mice during agonistic encounters. Eur J Neurosci 10: 3664-3672. (Pubitemid 29073923)
106. Pesce M, Speranza L, Franceschelli S, Ialenti V, Patruno A, et al. (2011) Biological role of interleukin-1beta in defensive-aggressive behaviour. J Biol Regul Homeost Agents 25: 323-329.
107. Hassanain M, Bhatt S, Zalcman S, Siegel A (2005) Potentiating role of interleukin-1beta (IL-1beta) and IL-1beta type 1 receptors in the medial hypothalamus in defensive rage behavior in the cat. Brain Res 1048: 1-11. (Pubitemid 40800254)