Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults.
Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus-pituitary-adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects. We present recent evidence related to epigenetic regulation of genes involved in hypothalamus-pituitary-adrenal axis regulation, namely, the glucocorticoid receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506 binding protein 51 gene (FKBP5), after childhood adversity and associations with risk for psychiatric disorders. Implications for the development of interventions and future research are discussed.
Butler Hospital.
Audrey R
AR
Tyrka
Butler Hospital.
Kathryn K
KK
Ridout
Brown University Alpert Medical School.
Stephanie H
SH
Parade
D000328:Adult; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D001523:Mental Disorders / Q000235:genetics / Q000523:psychology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D012931:Social Environment; D013315:Stress, Psychological / Q000150:complications* / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D000099159:Tacrolimus Binding Protein 5
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C497713:NR3C1 protein, human
Psychoneuroendocrinology. 2000 Jan;25(1):1-35
10633533
J Clin Psychiatry. 2001;62 Suppl 17:41-6
11495096
Dev Psychopathol. 2001 Summer;13(3):515-38
11523846
FASEB J. 2002 Jan;16(1):61-71
11772937
Biol Psychiatry. 2002 Sep 1;52(5):393-403
12242055
J Biol Chem. 2003 Jun 6;278(23):20812-20
12676953
J Biol Chem. 2003 Jul 25;278(30):27586-92
12748177
J Psychiatr Res. 2003 Nov-Dec;37(6):471-7
14563378
Neuropsychopharmacology. 2004 Feb;29(2):433-9
14666121
Biol Psychiatry. 2004 Apr 1;55(7):745-51
15039004
J Psychiatry Neurosci. 2004 May;29(3):185-93
15173895
Nat Neurosci. 2004 Aug;7(8):847-54
15220929
Nat Rev Neurosci. 2005 Jun;6(6):463-75
15891777
Neurosci Biobehav Rev. 2005;29(4-5):649-74
15925698
Psychoneuroendocrinology. 2005 Nov;30(10):1010-6
15950390
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3480-5
16484373
J Biol Chem. 2006 Jun 9;281(23):15763-73
16606618
Neuroscience. 2006 Dec 1;143(2):387-93
16962717
Carcinogenesis. 2007 Mar;28(3):560-71
17012225
Psychol Bull. 2007 Jan;133(1):25-45
17201569
Neuron. 2007 Mar 15;53(6):857-69
17359920
Br J Nutr. 2007 Jun;97(6):1064-73
17433129
Physiol Rev. 2007 Jul;87(3):873-904
17615391
Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):892-905
17656028
Biol Psychiatry. 2007 Nov 15;62(10):1080-7
17662255
JAMA. 2007 Oct 10;298(14):1685-7
17925521
Psychoneuroendocrinology. 2008 Feb;33(2):227-37
18096322
Biol Psychiatry. 2008 Jun 15;63(12):1147-54
18339361
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5573-8
18391224
Epigenetics. 2008 Mar-Apr;3(2):97-106
18536531
Dev Psychopathol. 2008 Summer;20(3):737-43
18606029
Dev Psychopathol. 2008 Summer;20(3):845-59
18606034
Eur J Neurosci. 2008 Jul;28(2):389-98
18702710
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13614-9
18757738
Nucleic Acids Res. 2008 Dec;36(22):7207-18
19004867
Biol Psychiatry. 2009 Jul 1;66(1):69-75
19375070
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Aug 1;33(5):889-94
19389455
Nat Rev Neurosci. 2009 Jun;10(6):434-45
19401723
J Abnorm Child Psychol. 2009 Nov;37(8):1151-63
19533326
Brain Res. 2009 Aug 25;1286:1-12
19545546
Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S186-95
19560279
Am J Prev Med. 2009 Nov;37(5):389-96
19840693
Dialogues Clin Neurosci. 2009;11(3):239-55
19877493
Psychoneuroendocrinology. 2010 Jul;35(6):878-86
20036072
Arch Gen Psychiatry. 2010 Feb;67(2):113-23
20124111
J Psychiatr Res. 2010 Aug;44(11):732-40
20144464
Front Hum Neurosci. 2010 Jan 08;3:68
20161700
Psychoneuroendocrinology. 2010 Sep;35(8):1167-77
20223598
Psychoneuroendocrinology. 2011 Apr;36(3):415-25
20399565
J Neurosci. 2010 May 12;30(19):6726-31
20463234
J Child Psychol Psychiatry. 2010 Oct;51(10):1079-95
20546078
Biochem Pharmacol. 2010 Dec 15;80(12):1860-8
20599772
Psychopharmacology (Berl). 2010 Oct;212(3):405-17
20706708
Epigenetics. 2010 Nov-Dec;5(8):730-5
20716949
Psychopharmacology (Berl). 2011 Mar;214(1):367-75
20838776
Psychoneuroendocrinology. 2011 May;36(4):531-9
20888698
Psychiatry Res. 2010 Nov 30;184(2):117-27
20934312
Horm Behav. 2011 Jan;59(1):123-32
21056565
Am J Psychiatry. 2011 Jan;168(1):89-96
21078706
PLoS One. 2011 Jan 18;6(1):e14524
21267076
Clin Child Fam Psychol Rev. 2011 Jun;14(2):135-60
21290178
Curr Opin Pharmacol. 2011 Aug;11(4):308-13
21514887
Genes Dev. 2011 May 15;25(10):1010-22
21576262
Eur Neuropsychopharmacol. 2011 Nov;21(11):796-809
21741804
Dev Psychopathol. 2011 Aug;23(3):789-800
21756432
Endocrinology. 2011 Dec;152(12):4496-503
21971152
Epigenetics. 2011 Dec;6(12):1454-62
22139575
PLoS One. 2012;7(1):e30481
22272355
PLoS One. 2012;7(1):e30148
22295073
Psychoneuroendocrinology. 2012 Sep;37(9):1439-47
22365483
Biol Psychiatry. 2012 Jul 1;72(1):41-8
22444201
Braz J Med Biol Res. 2012 Apr;45(4):292-8
22450375
Clin Psychol Rev. 2012 Jun;32(4):301-15
22459791
Biol Psychiatry. 2012 Sep 15;72(6):466-75
22572034
Psychoneuroendocrinology. 2012 Dec;37(12):2042-6
22575356
Curr Pharm Des. 2012;18(35):5663-74
22632471
Neuropsychopharmacology. 2013 Jan;38(1):23-38
22781841
Epigenetics. 2012 Aug;7(8):853-7
22810058
Transl Psychiatry. 2011 Jul 19;1:e21
22832523
World J Pediatr. 2012 Aug;8(3):197-206
22886191
Neuropsychopharmacology. 2013 Jan;38(1):111-23
22968814
Epigenetics. 2012 Nov;7(11):1290-301
23023726
J Neurosci. 2012 Oct 31;32(44):15626-42
23115197
Neurosci Lett. 2013 Jan 15;533:17-22
23178190
Nat Neurosci. 2013 Jan;16(1):33-41
23201972
Genes Brain Behav. 2013 Apr;12(3):289-96
23406438
Int J Eat Disord. 2013 Apr;46(3):246-55
23417893
Dev Psychobiol. 2014 Apr;56(3):392-406
23460384
Psychiatr Clin North Am. 2013 Mar;36(1):1-13
23538072
J Psychiatr Res. 2013 Jul;47(7):880-91
23566423
Acta Psychiatr Scand. 2013 Dec;128(6):434-47
23662634
Eur Child Adolesc Psychiatry. 2014 Jan;23(1):3-12
23771272
Dev Psychol. 2014 Mar;50(3):784-93
23895168
Front Psychiatry. 2013 Aug 01;4:78
23914177
Neuroscience. 2014 Apr 4;264:142-56
23933308
Trends Pharmacol Sci. 2013 Sep;34(9):518-30
23953592
Front Psychiatry. 2013 Sep 27;4:118
24098286
Epigenetics. 2013 Dec;8(12):1321-9
24135662
Neurosci Biobehav Rev. 2014 Jan;38:17-37
24216122
Genes Brain Behav. 2014 Jan;13(1):25-37
24219237
Dev Psychopathol. 2013 Nov;25(4 Pt 1):931-41
24229540
Infant Ment Health J. 2013 May;34(3):
24319304
Can J Psychiatry. 2013 Dec;58(12):697-704
24331290
Dev Psychopathol. 2013 Nov;25(4 Pt 2):1359-73
24342845
Dev Psychopathol. 2013 Nov;25(4 Pt 2):1619-34
24342859
J Pediatr. 2014 Mar;164(3):631-8.e1-2
24345452
Pediatrics. 2014 Feb;133(2):312-26
24420810
Paediatr Child Health. 2013 Oct;18(8):415-8
24426793
PLoS One. 2014 Jan 21;9(1):e85425
24465557
FASEB J. 2014 May;28(5):2088-97
24478308
Neuropsychiatr Dis Treat. 2014 Feb 03;10:243-8
24523589
Transl Psychiatry. 2014 Mar 04;4:e368
24594779
J Am Acad Child Adolesc Psychiatry. 2014 Apr;53(4):417-24.e5
24655651
Child Adolesc Psychiatr Clin N Am. 2014 Apr;23(2):185-222, vii
24656576
Biol Psychiatry. 2015 Feb 15;77(4):356-64
24661442
Transl Psychiatry. 2014 Apr 08;4:e381
24713862
Int J Dev Neurosci. 2014 Aug;36:5-12
24721039
J Affect Disord. 2014 Aug;164:33-7
24856550
Eur Neuropsychopharmacol. 2015 May;25(5):682-702
24857313
Compr Psychiatry. 2014 Aug;55(6):1422-5
24889341
Dev Psychobiol. 2014 Sep;56(6):1406-15
24889670
J Neuroendocrinol. 2014 Oct;26(10):707-23
25039443
J Psychiatr Res. 2014 Oct;57:34-40
25048180
Child Dev. 2015 Jan-Feb;86(1):303-9
25056599
J Neurosci. 2014 Jul 30;34(31):10274-84
25080589
PLoS One. 2014 Aug 12;9(8):e104913
25115650
Biochim Biophys Acta. 2014 Nov;1839(11):1051-61
25150144
Perspect Psychol Sci. 2013 Nov;8(6):673-5
25221612
Behav Neurosci. 2014 Dec;128(6):736-48
25244085
Front Neuroendocrinol. 2015 Jan;36:150-64
25256348
PLoS One. 2014 Oct 13;9(10):e106960
25310187
Biology (Basel). 2014 Oct 22;3(4):670-723
25340699
Dialogues Clin Neurosci. 2014 Sep;16(3):395-404
25364288
Neuroendocrinology. 2014;100(4):278-87
25427939
Neuroscience. 2015 Feb 12;286:141-50
25433240
JAMA Pediatr. 2015 Feb;169(2):112-9
25436448
J Am Acad Child Adolesc Psychiatry. 2014 Nov;53(11):1206-15
25440310
Behav Brain Res. 2015 Feb 15;279:123-8
25449846
Psychoneuroendocrinology. 2015 Feb;52:43-58
25459892
Psychoneuroendocrinology. 2015 Jan;51:426-30
25462914
Front Neurosci. 2014 Nov 21;8:369
25484853
Int J Neuropsychopharmacol. 2014 Oct 31;18(1):null
25522387
Int J Neuropsychopharmacol. 2014 Dec 13;18(4):null
25522420
Adv Psychosom Med. 2015;34:92-108
25832516
Epigenetics. 2015;10(5):408-17
25875334
J Affect Disord. 2015 Jul 15;180:97-103
25889020
Behav Genet. 2015 Sep;45(5):529-36
25894927
Cereb Cortex. 2016 Jun;26(6):2639-49
25976757
Dev Psychopathol. 2015 May;27(2):577-85
25997773
Neurosci Biobehav Rev. 2015 Aug;55:520-35
26073068
Neuropsychopharmacology. 2016 Jan;41(1):3-23
26076834
Child Dev. 2015 Sep-Oct;86(5):1311-20
26152664
Dev Psychobiol. 2015 Dec;57(8):935-47
26289841
Epigenetics. 2015;10(10):958-69
26295359
Behav Brain Res. 2016 Jan 1;296:286-289
26342282
Epigenomics. 2015 Aug;7(5):767-79
26343289
Nat Neurosci. 2015 Oct;18(10):1353-63
26404710
Biol Psychiatry. 2016 Sep 1;80(5):372-80
26410355
Transl Psychiatry. 2015 Oct 27;5:e668
26506054
Neuroscience. 2015 Dec 17;311:508-18
26548415
Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15544-5
26627713
Depress Anxiety. 2015 Dec;32(12):861-70
26647360
Neuropsychopharmacology. 2016 Jan;41(1):388-9
26657966
PLoS Genet. 2015 Dec 10;11(12):e1005661
26658498
Child Dev. 2016 Jan-Feb;87(1):61-72
26822443
Child Dev. 2016 Jan-Feb;87(1):73-85
26822444
Child Dev. 2016 Jan-Feb;87(1):86-97
26822445
Biol Psychiatry. 1988 Oct;24(6):619-30
3262379
Am J Psychiatry. 1985 Nov;142(11):1278-84
4061686
Psychiatry. 1993 Feb;56(1):96-118
8488217
Am J Prev Med. 1998 May;14(4):245-58
9635069