title: Behavioral epigenetics and the developmental origins of child mental health disorders.
abstract: Advances in understanding the molecular basis of behavior through epigenetic mechanisms could help explain the developmental origins of child mental health disorders. However, the application of epigenetic principles to the study of human behavior is a relatively new endeavor. In this paper we discuss the 'Developmental Origins of Health and Disease' including the role of fetal programming. We then review epigenetic principles related to fetal programming and the recent application of epigenetics to behavior. We focus on the neuroendocrine system and develop a simple heuristic stress-related model to illustrate how epigenetic changes in placental genes could predispose the infant to neurobehavioral profiles that interact with postnatal environmental factors potentially leading to mental health disorders. We then discuss from an 'Evo-Devo' perspective how some of these behaviors could also be adaptive. We suggest how elucidation of these mechanisms can help to better define risk and protective factors and populations at risk.
authors.affiliation: 1 Brown Center for the Study of Children at Risk at Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Lester
authors.affiliation: 5 Departments of Pharmacology & Toxicology and Community & Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Marsit
authors.affiliation: 1 Brown Center for the Study of Children at Risk at Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: E
authors.initials: E
authors.lastname: Conradt
authors.affiliation: 6 Department of Neuroscience, Brown University, Providence, RI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bromer
authors.affiliation: 3 Department of Pediatrics, Warren Alpen Medical School of Brown University, Providence, RI, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Padbury
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D002648:Child; D044127:Epigenesis, Genetic; D047109:Fetal Development; D006801:Humans; D001523:Mental Disorders / Q000209:etiology / Q000235:genetics*; D009490:Neurosecretory Systems / Q000502:physiology; D020641:Polymorphism, Single Nucleotide
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2
references.citation: Ann N Y Acad Sci. 2004 Dec;1032:63-84
references.pmid: 15677396
references.citation: Am J Epidemiol. 2007 Mar 1;165(5):575-82
references.pmid: 17148497
references.citation: Lancet. 1996 Nov 9;348(9037):1269-73
references.pmid: 8909379
references.citation: J Am Acad Child Adolesc Psychiatry. 2003 Sep;42(9):1116-21
references.pmid: 12960712
references.citation: Dev Med Child Neurol. 1973 Dec;15(6):770-87
references.pmid: 4129091
references.citation: J Nutr. 2005 Jun;135(6):1382-6
references.pmid: 15930441
references.citation: Physiol Behav. 1998 Feb 1;63(3):337-43
references.pmid: 9469724
references.citation: BMJ. 1995 Nov 4;311(7014):1203
references.pmid: 7488897
references.citation: Epigenetics. 2008 Mar-Apr;3(2):97-106
references.pmid: 18536531
references.citation: N Engl J Med. 1976 Aug 12;295(7):349-53
references.pmid: 934222
references.citation: Child Dev. 1993 Oct;64(5):1439-50
references.pmid: 8222882
references.citation: BMJ. 1989 Mar 4;298(6673):564-7
references.pmid: 2495113
references.citation: J Am Acad Child Adolesc Psychiatry. 1989 Mar;28(2):242-8
references.pmid: 2925579
references.citation: Am J Hypertens. 2002 Feb;15(2 Pt 2):43S-45S
references.pmid: 11866228
references.citation: Neurosci Biobehav Rev. 2005 Apr;29(2):237-58
references.pmid: 15811496
references.citation: Physiol Behav. 1990 Aug;48(2):289-92
references.pmid: 2255733
references.citation: Physiol Rev. 2005 Apr;85(2):571-633
references.pmid: 15788706
references.citation: J Neurosci. 1996 Jun 15;16(12):3943-9
references.pmid: 8656288
references.citation: Int J Neurosci. 1992 Feb;62(3-4):227-41
references.pmid: 1339051
references.citation: Lancet. 1989 Sep 9;2(8663):577-80
references.pmid: 2570282
references.citation: Nat Neurosci. 2000 Aug;3(8):799-806
references.pmid: 10903573
references.citation: Trends Neurosci. 2005 Sep;28(9):456-63
references.pmid: 16054244
references.citation: Pediatrics. 2006 Feb;117(2):309-16
references.pmid: 16452348
references.citation: J Comp Neurol. 1991 Nov 15;313(3):479-85
references.pmid: 1770171
references.citation: Pediatrics. 2010 Jan;125(1):e90-8
references.pmid: 19969621
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1966-74
references.pmid: 11705783
references.citation: BMJ. 2002 Oct 5;325(7367):749
references.pmid: 12364303
references.citation: FASEB J. 2007 Nov;21(13):3618-28
references.pmid: 17551100
references.citation: Pediatr Res. 2004 Sep;56(3):311-7
references.pmid: 15240866
references.citation: Am J Obstet Gynecol. 2004 Mar;190(3):588-95
references.pmid: 15041985
references.citation: Br J Psychiatry. 2004 Jan;184:28-33
references.pmid: 14702224
references.citation: Reproduction. 2009 Sep;138(3):601-8
references.pmid: 19525364
references.citation: Am J Occup Ther. 1998 Feb;52(2):90-8
references.pmid: 9494629
references.citation: Brain Behav Immun. 2009 Oct;23(7):905-16
references.pmid: 19217937
references.citation: Brain Res. 1992 Mar 6;574(1-2):131-7
references.pmid: 1322219
references.citation: Behav Brain Res. 1994 Dec 15;65(2):153-5
references.pmid: 7718147
references.citation: Science. 1984 Dec 14;226(4680):1342-4
references.pmid: 6334362
references.citation: Semin Neonatol. 2001 Aug;6(4):309-17
references.pmid: 11972432
references.citation: Dev Psychopathol. 2002 Summer;14(3):653-66
references.pmid: 12349878
references.citation: Acta Psychiatr Scand. 1990 Apr;81(4):364-71
references.pmid: 2343764
references.citation: Dev Neurosci. 2009;31(1-2):23-35
references.pmid: 19372684
references.citation: J Clin Invest. 2004 Oct;114(8):1146-57
references.pmid: 15489962
references.citation: J Neuroendocrinol. 1994 Jun;6(3):341-5
references.pmid: 7920600
references.citation: J Clin Endocrinol Metab. 1998 Jul;83(7):2244-54
references.pmid: 9661590
references.citation: Endocrinology. 2004 Sep;145(9):4068-72
references.pmid: 15205378
references.citation: Dev Med Child Neurol. 1994 Sep;36(9):826-32
references.pmid: 7926332
references.citation: Ment Retard Dev Disabil Res Rev. 2003;9(3):149-54
references.pmid: 12953293
references.citation: Lancet. 1982 Dec 4;2(8310):1259-64
references.pmid: 6128558
references.citation: Ann N Y Acad Sci. 2002 Dec;981:61-81
references.pmid: 12547674
references.citation: Acta Psychiatr Scand. 1985 Dec;72(6):505-11
references.pmid: 2417452
references.citation: Biol Reprod. 2009 Jun;80(6):1209-15
references.pmid: 19208548
references.citation: J Obstet Gynaecol. 2003 Sep;23(5):555-60
references.pmid: 12963520
references.citation: Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R131-7
references.pmid: 16987876
references.citation: Child Psychiatry Hum Dev. 1991 Winter;22(2):97-110
references.pmid: 1800027
references.citation: J Pediatr. 2010 Mar;156(3):366-71
references.pmid: 19880137
references.citation: Placenta. 1981 Oct-Dec;2(4):279-85
references.pmid: 6946410
references.citation: Epigenetics. 2011 May;6(5):566-72
references.pmid: 21521940
references.citation: Child Dev. 1994 Oct;65(5):1457-77
references.pmid: 7982362
references.citation: Ann Intern Med. 1999 Feb 16;130(4 Pt 1):278-84
references.pmid: 10068385
references.citation: Trends Endocrinol Metab. 2002 Nov;13(9):364-8
references.pmid: 12367816
references.citation: Lancet. 1998 Aug 29;352(9129):707-8
references.pmid: 9728994
references.citation: Ann N Y Acad Sci. 2006 Dec;1094:259-62
references.pmid: 17347357
references.citation: J Comp Neurol. 1991 Nov 15;313(3):486-93
references.pmid: 1770172
references.citation: Br J Psychiatry. 1998 Apr;172:324-6
references.pmid: 9715334
references.citation: J Perinatol. 2012 Apr;32(4):299-303
references.pmid: 21760584
references.citation: J Pediatr. 2010 Aug;157(2):288-295.e1
references.pmid: 20400094
references.citation: Int J Behav Dev. 2012 Jan 1;36(1):29-35
references.pmid: 22962506
references.citation: BMJ. 1991 Oct 26;303(6809):1019-22
references.pmid: 1954451
references.citation: Am J Clin Nutr. 1999 Nov;70(5):811-6
references.pmid: 10539740
references.citation: Neurosci Biobehav Rev. 2010 Sep;35(1):23-32
references.pmid: 19931557
references.citation: Br J Psychiatry. 2001 Nov;179:450-5
references.pmid: 11689404
references.citation: Science. 2010 May 28;328(5982):1161-4
references.pmid: 20508129
references.citation: J Anim Sci. 2000 Sep;78(9):2399-411
references.pmid: 10985416
references.citation: Biochem Pharmacol. 1987 Jun 1;36(11):1755-63
references.pmid: 3555503
references.citation: Lancet. 1993 Feb 6;341(8841):355-7
references.pmid: 8094124
references.citation: J Clin Endocrinol Metab. 1995 Mar;80(3):885-90
references.pmid: 7883847
references.citation: Prog Brain Res. 2001;133:131-42
references.pmid: 11589126
references.citation: Dev Psychobiol. 2013 Nov;55(7):673-83
references.pmid: 22714792
references.citation: J Clin Endocrinol Metab. 2002 Apr;87(4):1660-8
references.pmid: 11932298
references.citation: Kidney Int. 2000 Apr;57(4):1412-7
references.pmid: 10760076
references.citation: J Pediatr. 2012 May;160(5):854-860.e2
references.pmid: 22153677
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: Physiol Behav. 2003 Jul;79(2):209-15
references.pmid: 12834792
references.citation: Physiol Rev. 1985 Oct;65(4):946-1020
references.pmid: 2414792
references.citation: Steroids. 1997 Jan;62(1):89-94
references.pmid: 9029721
references.citation: Dev Psychopathol. 2005 Spring;17(2):271-301
references.pmid: 16761546
references.citation: Child Dev. 2003 Sep-Oct;74(5):1534-46
references.pmid: 14552412
references.citation: Hum Reprod. 1998 Apr;13(4):799-804
references.pmid: 9619527
references.citation: Nat Neurosci. 2004 Aug;7(8):847-54
references.pmid: 15220929
references.citation: Neuroscience. 1980;5(11):2003-12
references.pmid: 7432634
references.citation: Eur J Neurosci. 1999 Aug;11(8):2906-16
references.pmid: 10457187
references.citation: Physiol Behav. 1988;43(2):139-43
references.pmid: 3212048
references.citation: Child Dev. 2013 Jan-Feb;84(1):58-75
references.pmid: 21883162
references.citation: J Pharmacol Exp Ther. 1987 Feb;240(2):602-11
references.pmid: 2433431
references.citation: Psychoneuroendocrinology. 1995;20(2):149-67
references.pmid: 7899535
references.citation: Pediatr Res. 2011 Aug;70(2):213-9
references.pmid: 21546861
references.citation: Neuropsychopharmacology. 2008 Feb;33(3):536-45
references.pmid: 17507916
references.citation: Pediatrics. 1995 Apr;95(4):516-21
references.pmid: 7700751
references.citation: Child Dev. 2004 Jan-Feb;75(1):96-109
references.pmid: 15015677
references.citation: Atherosclerosis. 2008 Aug;199(2):323-7
references.pmid: 18178212
references.citation: Ann N Y Acad Sci. 2011 May;1226:14-33
references.pmid: 21615751
references.citation: Br J Psychiatry. 2005 Jul;187:21-8
references.pmid: 15994567
references.citation: J Child Psychol Psychiatry. 2003 Sep;44(6):810-8
references.pmid: 12959490
references.citation: Int J Dev Neurosci. 1998 Jun-Jul;16(3-4):209-16
references.pmid: 9785117
references.citation: Mol Endocrinol. 2002 Aug;16(8):1719-26
references.pmid: 12145329
references.citation: Ann N Y Acad Sci. 2004 Dec;1032:228-30
references.pmid: 15677416
references.citation: J Cell Physiol. 2010 Aug;224(2):311-5
references.pmid: 20432441
references.citation: J Neuroendocrinol. 2001 Feb;13(2):113-28
references.pmid: 11168837
references.citation: Psychol Bull. 2005 May;131(3):340-60
references.pmid: 15869332
references.citation: N Engl J Med. 1998 Jan 15;338(3):171-9
references.pmid: 9428819
references.citation: Science. 2004 Sep 17;305(5691):1733-6
references.pmid: 15375258
references.citation: J Clin Endocrinol Metab. 2008 Dec;93(12):4887-93
references.pmid: 18728163
references.citation: Am J Prev Med. 1998 May;14(4):245-58
references.pmid: 9635069
references.citation: Nature. 2007 May 24;447(7143):396-8
references.pmid: 17522671
references.citation: Placenta. 1997 Mar-Apr;18(2-3):205-10
references.pmid: 9089783
references.citation: J Neurosci. 2006 Apr 5;26(14):3840-4
references.pmid: 16597738
references.citation: Soc Sci Med. 2002 Sep;55(6):937-48
references.pmid: 12220095
references.citation: J Clin Endocrinol Metab. 2001 Oct;86(10):4979-83
references.pmid: 11600574
references.citation: Placenta. 2004 Jul;25(6):518-29
references.pmid: 15135235
references.citation: Dev Med Child Neurol. 2011 Sep;53 Suppl 4:19-23
references.pmid: 21950389
references.citation: Dev Psychopathol. 2011 Feb;23(1):29-38
references.pmid: 21262037
references.citation: Physiol Behav. 1995 May;57(5):989-94
references.pmid: 7610154
references.citation: Physiol Behav. 1992 Feb;51(2):319-23
references.pmid: 1313590
references.citation: Neurosci Biobehav Rev. 2005;29(4-5):843-65
references.pmid: 15893378
references.citation: Dev Psychobiol. 1992 Nov;25(7):529-40
references.pmid: 1459346
references.citation: BMJ. 1988 Jul 9;297(6641):134-5
references.pmid: 3408942
references.citation: J Neurosci. 1997 Apr 1;17(7):2626-36
references.pmid: 9065522
references.citation: Dev Psychobiol. 1996 Jul;29(5):453-62
references.pmid: 8809495
references.citation: Lancet. 1993 Feb 6;341(8841):339-41
references.pmid: 8094115
references.citation: BMC Bioinformatics. 2008 Sep 09;9:365
references.pmid: 18782434
references.citation: Semin Perinatol. 1988 Apr;12(2):163-72
references.pmid: 3293227
references.citation: J Neurosci. 1995 Jan;15(1 Pt 1):110-6
references.pmid: 7823121
references.citation: Dev Psychol. 1998 Nov;34(6):1417-27
references.pmid: 9823521
references.citation: Biol Psychiatry. 1997 Jan 1;41(1):23-32
references.pmid: 8988792
references.citation: Pediatrics. 2004 Mar;113(3 Pt 2):641-67
references.pmid: 14993524
references.citation: Physiol Behav. 1986;37(5):681-7
references.pmid: 3774900
references.citation: Am J Obstet Gynecol. 2004 Oct;191(4):1063-9
references.pmid: 15507922
references.citation: Dev Psychol. 2007 Jan;43(1):1-12
references.pmid: 17201504
references.citation: Trends Endocrinol Metab. 2002 Nov;13(9):373-80
references.pmid: 12367818
references.citation: PLoS One. 2012;7(3):e33794
references.pmid: 22432047