Defense Date

2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pathology

First Advisor

Colleen Jackson-Cook

Abstract

The primary study aim was to evaluate the latent biological effect of childhood sexual abuse (CSA) on adults by quantifying acquired cytogenetic changes and cortisol levels in identical twins who were discordant (N=22) or concordant (N=2) for a history of CSA. Although the difference scores for cortisol values between discordant identical co-twins were not significantly different from zero, a trend was observed for the twins exposed to intercourse, the most severe form of CSA, to have a blunted cortisol awakening response. Acquired cytogenetic changes were assessed by scoring telomere lengths and somatic cell abnormality frequencies via a cytokinesis-block micronucleus (MN) assay. No significant difference in overall telomere intensity values was observed between co-twins, but chromosome-specific telomere differences were observed in the individuals exposed to intercourse compared to their unabused co-twins ([χ2(45)= 62.88; p= 0.040 and χ2(45)= 73.72; p= 0.004). Specifically, shortened telomeres were observed on the short arms of chromosomes 3, 5, & 6, and long arms of chromosomes 11 & 13. A significant increase in MN frequencies was observed in the abused twins compared to unabused twins (t=2.65; df=16; p=0.009). A significant interaction between micronuclei frequencies and age was also observed, suggesting that the biological effects of stress are cumulative (coefficient [SE] = 0.030 [0.009]; p=0.0006). However, the pattern of chromatin present in MN, which was assessed using spectral karyotyping methodologies, was not limited to the subset of chromosomes with telomeric attrition. In summary, this is the first assessment of acquired chromosomal abnormalities, chromosome-specific telomere lengths and cortisol levels in identical adult twins discordant for exposure to CSA. Given that a portion of biological changes were most pronounced in the intercourse discordant twins, these findings support a possible dose-response relationship with CSA severity. Our data also suggest that the MN assay is a superior tool in assessing the latent effects of stress compared to either cortisol profiling or the measurement of telomere lengths. Collectively, application of the information gained from these studies may allow for novel screening techniques to identify individuals who are most at risk for developing stress-associated disease states.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

9-23-2011

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