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Addressing Issues in the Detection of Gene-Environment Interaction Through the Study of Conduct DisorderProm, Elizabeth Chin 01 January 2007 (has links)
This work addresses issues in the study of gene-environment interaction (GxE) through research of conduct disorder (CD) among adolescents and extends the recent report of significant GxE and subsequent replication studies. A sub-sample of 1,299 individual participants/649 twin pairs and their parents from the Virginia Twin Study of Adolescent and Behavioral Development was used for whom Monoamine Oxidase A (MAOA) genotype, diagnosis of CD, maternal antisocial personality symptoms, and household neglect were obtained. This dissertation (1) tested for GxE by gender using MAOA and childhood adversity using multiple approaches to CD measurement and model assessment, (2) determined whether other mechanisms would explain differences in GxE by gender and (3) identified and assessed other genes and environments related to the interaction MAOA and childhood adversity. Using a multiple regression approach, a main effect of the low/low MAOA genotype remained after controlling other risk factors in females. However, the effects of GxE were modest and were removed by transforming the environmental measures. In contrast, there was no significant effect of the low activity MAOA allele in males although significant GxE was detected and remained after transformation. The sign of the interaction for males was opposite from females, indicating genetic sensitivity to childhood adversity may differ by gender. Upon further investigation, gender differences in GxE were due to genotype-sex interaction and may involve MAOA. A Markov Chain Monte Carlo approach including a genetic Item Response Theory modeled CD as a trait with continuous liability, since false detection of GxE may result from measurement. In males and females, the inclusion of GxE while controlling for the other covariates was appropriate, but was little improvement in model fit and effect sizes of GxE were small. Other candidate genes functioning in the serotonin and dopamine neurotransmitter systems were tested for interaction with MAOA to affect risk for CD. Main genetic effects of dopamine transporter genotype and MAOA in the presence of comorbidity were detected. No epistatic effects were detected. The use of random forests systematically assessed the environment and produced several interesting environments that will require more thoughtful consideration before incorporation into a model testing GxE.
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Studying individual differences and emotion regulation effects on PTSD-like responding and recovery : a psychophysiological VR-trauma paradigmRumball, Freya January 2013 (has links)
Despite a high proportion of the population experiencing traumatic events within their lifetime, the number of individuals who go on to develop posttraumatic stress disorder (PTSD) is comparatively small; herein highlighting the importance of individual differences in imparting risk and resilience towards the development and maintenance of PTSD. Existing literature illustrates that biological and ecological factors are important in predicting PTSD development, with pathological vulnerabilities excepting their effects at pre- peri- and post trauma stages. Whilst cognitive and emotion based models of PTSD account for the role of a minority of known pre-trauma risk factors, individual differences in peri- and post trauma processes are held as critical to the development of PTSD. The broad range of risk factors implicated in the empirical literature, and necessity of traumatic exposure to PTSD, implicates the utility of a diathesis-stress conceptualisation of PTSD development. The current thesis employed an analogue VR-trauma paradigm to investigate the respective importance of vulnerability factors at each stage, in the prediction of analogue PTSD symptoms (memory problems, startle responses, re-exposure fear habituation), whilst measuring affective and electrophysiological concomitance. Findings supported the importance of peri-traumatic responses in the prediction of PTSD, where present, showing increased predictive capacities over pre- and post-trauma factors. Biological and ecological factors also illustrated important predictive associations, with genetic SNPs implicated in reflex startle and cardiac responses towards intrusive memories. Moreover, peri-traumatic HR decelerations and accelerations mediated the association between pre-trauma factors and cued recall inaccuracy and intrusion severity respectively. Results support existing cognitive and emotional models in their emphasis on peri-traumatic processes but suggest the added utility of a diathesis stress conceptualisation of the development of PTSD, in highlighting the importance of pre-trauma biological and ecological risk and resilience factors.
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