Childhood sexual abuse (CSA) not only compromises well-being in childhood but is also associated with a broad range of psychopathology and morbidity in adulthood 
. However, little is known about the biological mechanisms involved in mediating the long-term pathogenic effect of early-life trauma. One possible means for CSA to be biologically “embedded” in a manner that could lead to a latent pathologic consequence would be if it resulted in a change in the individual’s somatic cell DNA. Evidence shows childhood maltreatment predicts an increased risk of clinically relevant levels of inflammation in adulthood 
, and inflammation-associated reactive oxygen/nitrogen species are known to cause DNA damage/chromosomal changes. Stress-related inflammation also leads to perturbations in the regulation/expression of several genes, including (but not limited to) nuclear factor-kappa B (NF-kβ), interleukin-1B, interleukin-6, and tumor necrosis factor-α 
. Additional evidence that early-life stress can lead to DNA-based alterations comes from reports of shortened telomeres in children exposed to adverse rearing settings 
, and in adults with a history of chronic or severe childhood illness 
or childhood maltreatment 
, but the potential correlation between childhood maltreatment and telomere length is controversial 
Given that both telomere shortening and/or inflammation-related generation of oxygen and/or nitrogen species are phenomena that have been associated with an increased frequency of acquired chromosomal abnormalities 
, we hypothesize that an alternative or additional biological effect of stress could be the acquisition of somatic cell chromosomal instability. Moreover, since such damage can cause mutations and chromosomal abnormalities that disrupt cellular function and viability through aberrant gene expression and protein formation 
, the accumulation of chromosomal imbalances over time provides a plausible account by which CSA exposure could contribute to the development of later health and psychiatric symptoms observed in adults with a CSA history.
The cytokinesis-block micronucleus (CBMN) assay is an attractive biomarker for estimating chromosomal damage associated with environmental insults or exposures and is considered an acceptable alternative to data obtained from the assessment of metaphase chromosomal analyses 
, since it is less labor intensive and less prone to producing artifacts than classical chromosomal studies 
. Briefly, a micronucleus (MN) is a small chromatin-containing structure that can be visualized juxtaposed to the main daughter nuclei following the completion of mitosis (). MN formation can occur spontaneously or in response to environmental exposures and can accumulate over several months or years 
. MN form when whole chromosomes or chromosomal fragments fail to correctly migrate to spindle poles during mitosis 
. The lagging chromosome(s) or fragment(s) are subsequently excluded from the daughter nuclei and are encased in their own nuclear envelope 
. The exclusion of chromatin into a MN can result in alterations of cellular gene dosage, which, in turn, could result in abnormal gene expression and/or perturbations in cellular proliferation that could have a broad cascade of consequences on biological systems 
. MN frequency is known to increase with age 
and has been shown to be elevated in patients with several health conditions, including cancer 
, cardiovascular disease 
, Alzheimer’s disease and Parkinson’s disease 
Giemsa stained micronucleus (MN) (arrow) and corresponding daughter binucleates.
MN frequency is influenced by both heritable genetic and environmental factors 
. However, the extent to which MN frequency is impacted by exposure to a traumatic event, such as CSA, is not known. One of the most robust approaches to determine the causal role of non-genetic influences on trait variation is to study monozygotic (MZ) twins who are discordant for exposure histories. Theoretically, because the DNA of MZ twins differs only for induced changes, they provide a unique opportunity to study the long-term biological impact of childhood traumatic events.
In the present study we tested the hypothesis that adult females who experienced CSA have a higher frequency of spontaneously occurring leukocyte MN than their identical twins who did not experience CSA. Although these twin pairs are quite rare, we elected to use a discordant identical twin study design since it allows one to control for known genetic influences on MN formation 
and provides an effective means for separating the causal effects of CSA from background familial risk factors known to associate with CSA.