Oxytocin Genetic and Epigenetic Variation: Association with Social Adversity and Behavioral and Health Outcomes Público

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

About this Dissertation

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School	Laney Graduate School
Department	Behavioral Sciences and Health Education
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Psychology, Psychobiology Biology, Genetics Psychology, Behavioral
Palavra-chave	Intervention Stress Oxytocin Epigenetics Genetics
Committee Chair / Thesis Advisor	Brennan, Patricia, Emory University Sales, Jessica, Emory University
Committee Members	Brody, Gene H., Emory University Johnson, Katrina, Emory University Smith, Alicia K, Emory University

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