Oxytocin Genetic and Epigenetic Variation: Association with Social Adversity and Behavioral and Health Outcomes Open Access
Smearman, Erica Lauren (2015)
Abstract
Exposure to environmental stress can increase an individual's risk for behavioral problems, psychopathology, and chronic health conditions. Importantly individuals with different genetic profiles vary in their responsiveness to these environments, and thus their likelihood of developing adverse outcomes. Given the social nature of many stressful environments, genetic factors related to the oxytonergic system may be relevant to environmental differential susceptibility. Oxytocin is a hormone important for perceiving social cues. Therefore, the oxytonergic system may influence perception of, and thus sensitivity towards, both nurturing and adverse social environments. While much of the initial human oxytocin work draws from positive social environments, more recent work has incorporated adverse social contexts. This dissertation expands this literature, exploring genetic differences in the oxytocin receptor gene (sequence variation and methylation patterns) in the association between adverse social environments and behavioral and health outcomes, including responsiveness to intervention. First, in a prospective cohort of youth (N=404), we tested the role of OXTR genetics in the association between interpersonal conflict and conduct and antisocial behaviors at age 15 and 20, finding that individuals with the rs53576 GG genotype engaged in more disordered behavior when exposed to high levels of interpersonal conflict. Second, in a sample of adults (N=393), we assessed the role of OXTR DNA methylation in the association between abuse and psychopathology, finding that individuals with specific OXTR CpG methylation patterns reported higher levels of depression and anxiety when exposed to abuse, compared to those without those patterns. OXTR sequence variation and methylation were also considered together, with OXTR genotypes associating with methylation of nearby CpG sites. Third, in a sample of parent-youth pairs (N=191), we explored the role of OXTR genetics on responsiveness to a family-based intervention. Youth with the rs53576 GG genotype again showed the greatest sensitivity to environmental context, exhibiting the shortest telomeres when exposed to high parent-youth conflict and randomized to the control intervention condition, and telomere lengths similar to the non at-risk group when randomized to the intervention. The combined findings suggest a role for OXTR in sensitivity to the social environment and in the prediction of behavioral and health outcomes.
Table of Contents
CHAPTER 1: Introductory Literature Review 1
Genetics 2
Differential Susceptibility 3
Epigenetics 4
Differential Susceptibility and Epigenetics 5
Epigenetics and the Environment 5
Role of Oxytocin 6
Oxytocin Genetics 9
OXTRrs535769 OXTRE pigenetics 10
OXTR Epigenetics in Humans 11
Prevention & OXTR 12
Summary 12
References 14
CHAPTER 2: Social stress and the oxytocin receptor gene interact to predict antisocial behavior in an at-risk cohort 23
Abstract 24
Introduction 25
Methods 27
Results 33
Discussion 34
References 40
CHAPTER 3: Oxytocin receptor genetic and epigenetic variation: association with child abuse and adult psychiatric symptoms 52
Abstract 53
Introduction 54
Methods 56
Results 60
Discussion 63
References71
CHAPTER 4: Variation in the Oxytocin Receptor Gene Moderates the Protective Effects of a Family-Based Prevention Program on Telomere Length 85
Abstract 86
Introduction 87
Methods 90
Results 95
Discussion 97
References 101
CHAPTER 5: Summary and Conclusions 110
References 122
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