title: Increased frequency of micronuclei in adults with a history of childhood sexual abuse: a discordant monozygotic twin study.
abstract: BACKGROUND
  Childhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA.
  
  
  METHODS
  Monozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a reference sample). Micronuclei (MN) contain chromatin from structurally normal or abnormal chromosomes that are excluded from the daughter nuclei during cell division and serve as a biomarker to assess acquired chromosomal instability.
  
  
  RESULTS
  Female twins exposed to CSA exhibited a 1.63-fold average increase in their frequency of MN compared to their nonexposed genetically identical cotwins (Paired t-test, t₁₆ = 2.65, P = 0.017). No additional effects of familial factors were detected after controlling for the effect of CSA exposure. A significant interaction between CSA history and age was observed, suggesting that the biological effects of CSA on MN formation may be cumulative.
  
  
  CONCLUSIONS
  These data support a direct link between CSA exposure and MN formation measured in adults that is not attributable to genetic or environmental factors shared by siblings. Further research is warranted to understand the biological basis for the observed increase in acquired chromosomal findings in people exposed to CSA and to determine if acquired somatic chromosomal abnormalities/somatic clonal mosaicism might mediate the adult pathology associated with CSA.
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America. tpyork@vcu.edu
authors: Timothy P
authors: TP
authors: York
authors: Jenni
authors: J
authors: Brumelle
authors: Jane
authors: J
authors: Juusola
authors: Kenneth S
authors: KS
authors: Kendler
authors: Lindon J
authors: LJ
authors: Eaves
authors: Ananda B
authors: AB
authors: Amstadter
authors: Steven H
authors: SH
authors: Aggen
authors: Kimberly H
authors: KH
authors: Jones
authors: Andrea
authors: A
authors: Ferreira-Gonzalez
authors: Colleen
authors: C
authors: Jackson-Cook
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002650:Child Abuse, Sexual / Q000706:statistics & numerical data*; D043171:Chromosomal Instability / Q000502:physiology*; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D048629:Micronuclei, Chromosome-Defective / Q000706:statistics & numerical data*; D015162:Micronucleus Tests; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D014768:Virginia
references: Mol Psychiatry. 2012 Jul;17(7):719-27
references: 21577215
references: Neurol Sci. 2002 Sep;23 Suppl 2:S97-8
references: 12548361
references: Front Psychiatry. 2011 Jul 28;2:48
references: 21847382
references: J Cell Biol. 2001 Jul 9;154(1):49-60
references: 11448989
references: Mutat Res. 1998 Feb;410(1):81-116
references: 9587425
references: Cytogenet Cell Genet. 1997;76(3-4):196-201
references: 9186523
references: Mutagenesis. 2011 Jan;26(1):125-32
references: 21164193
references: Mutagenesis. 1998 May;13(3):235-41
references: 9643581
references: Mutagenesis. 2011 Nov;26(6):745-52
references: 21765037
references: Mutagenesis. 2001 Mar;16(2):109-14
references: 11230551
references: Psychol Bull. 2011 Nov;137(6):959-97
references: 21787044
references: Psychol Sci. 2011 Oct;22(10):1343-52
references: 21948854
references: Am J Psychiatry. 1998 Aug;155(8):1016-22
references: 9699687
references: Mutat Res. 2000 Nov 20;455(1-2):81-95
references: 11113469
references: Am J Cardiol. 2008 Nov 15;102(10):1296-300
references: 18993144
references: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6143-7
references: 15837924
references: Arch Gen Psychiatry. 2010 Feb;67(2):111-2
references: 20124110
references: Curr Genomics. 2008 Nov;9(7):452-65
references: 19506734
references: BMC Cancer. 2011 May 26;11:199
references: 21612665
references: Mutat Res. 2007 Apr 1;617(1-2):33-45
references: 17250856
references: Mutat Res. 2003 Jan 10;534(1-2):65-75
references: 12504755
references: Mutat Res. 1985 Jan-Feb;148(1-2):99-105
references: 3918259
references: Environ Mol Mutagen. 2001;37(1):31-45
references: 11170240
references: Mutat Res. 1991 Mar-Nov;256(2-6):271-82
references: 1722017
references: Biochimie. 2006 Nov;88(11):1515-31
references: 16919864
references: Nat Genet. 1999 Jun;22(2):168-70
references: 10369259
references: Biol Psychiatry. 2010 Sep 15;68(6):e21-2; author reply e23-4
references: 20678755
references: Methods Mol Biol. 2009;512:15-28
references: 19347270
references: Arch Gen Psychiatry. 2002 Feb;59(2):139-45
references: 11825135
references: Mutagenesis. 2011 Jan;26(1):63-7
references: 21164184
references: Arch Gen Psychiatry. 1999 Jan;56(1):39-44
references: 9892254
references: Arch Gen Psychiatry. 2000 Oct;57(10):953-9
references: 11015813
references: JAMA. 2000 Nov 8;284(18):2321
references: 11066180
references: Cytogenet Cell Genet. 1983;36(3):554-61
references: 6196158
references: Mech Ageing Dev. 2004 Aug;125(8):563-73
references: 15336914
references: Mol Cytogenet. 2008 Nov 25;1:26
references: 19032785
references: Psychol Bull. 2007 Jan;133(1):25-45
references: 17201569
references: Biol Psychiatry. 2010 Mar 15;67(6):531-4
references: 19828140
references: PLoS One. 2010 May 25;5(5):e10826
references: 20520834
references: Mech Ageing Dev. 2011 Aug;132(8-9):429-36
references: 21549743
references: Arch Toxicol. 2011 Aug;85(8):873-99
references: 21537955
references: Arch Gen Psychiatry. 1992 Apr;49(4):257-66
references: 1558459
references: Environ Mol Mutagen. 1989;13(1):34-43
references: 2783409
references: Oncogene. 1998 Apr 9;16(14):1825-38
references: 9583680
references: Langenbecks Arch Surg. 2006 Sep;391(5):499-510
references: 16909291
references: Br J Psychiatry. 2001 Nov;179:444-9
references: 11689403
references: Carcinogenesis. 1998 Feb;19(2):259-65
references: 9498274
references: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1319-24
references: 17229839
references: J Med Genet. 1995 Jul;32(7):502-8
references: 7562960
references: Psychol Med. 2000 Jan;30(1):41-52
references: 10722174
references: Mutagenesis. 2011 Jan;26(1):111-7
references: 21164191
references: Diagn Cytopathol. 2012 Jan;40(1):84-90
references: 22180242
references: Curr Genomics. 2008 Mar;9(1):43-50
references: 19424483
references: Mutat Res. 2001 Aug 22;495(1-2):11-9
references: 11448638
references: Mutat Res. 2007 Aug 1;621(1-2):113-8
references: 17448506
references: Genes Chromosomes Cancer. 2001 Mar;30(3):236-44
references: 11170280
references: Child Abuse Negl. 1993 May-Jun;17(3):383-92
references: 8330225
references: Trends Genet. 2011 Jun;27(6):217-23
references: 21496937
references: Mutagenesis. 2008 Nov;23(6):423-37
references: 18678752
references: Mutagenesis. 2011 Jan;26(1):27-32
references: 21164179
references: Carcinogenesis. 2007 Mar;28(3):625-31
references: 16973674
references: EMBO J. 1992 May;11(5):1921-9
references: 1582420