ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Genetic and environmental factors interact to influence vulnerability for internalizing psychopathology, including Major Depressive Disorder (MDD). The mechanisms that account for how environmental stress can alter biological systems are not yet well understood yet are critical to develop more accurate models of vulnerability and targeted interventions. Epigenetic influences, and more specifically, DNA methylation, may provide a mechanism by which stress could program gene expression, thereby altering key systems implicated in depression, such as frontal-limbic circuitry and its critical role in emotion regulation. This thesis investigated the role of environmental factors from infancy and throughout the lifespan affecting the serotonergic (5-HT) system in the vulnerability to and treatment of depression and anxiety and potential underlying DNA methylation processes. First, we investigated the contributions of additive genetic vs. environmental factors on an early trait phenotype for depression (negative emotionality) in infants and their stability over time in the first 2 years of life. We provided evidence of the substantial contributions of both genetic and shared environmental factors to this trait, as well as genetically- and environmentally- mediated stability and innovation. Second, we studied how childhood environmental stress is associated with peripheral DNA methylation of the serotonin transporter gene, SLC6A4, as well as long-term trajectories of internalizing behaviours. There was a relationship between childhood psychosocial adversity and SLC6A4 methylation in males, as well as between SLC6A4 methylation and internalizing trajectory in both sexes. Third, we investigated changes in emotion processing and epigenetic modification of the SLC6A4 gene in depressed adolescents before and after Mindfulness-Based Cognitive Therapy (MBCT). The alterations from pre- to post-treatment in connectivity between the ACC and other network regions and SLC6A4 methylation suggested that MBCT may work to optimize the connectivity of brain networks involved in cognitive control of emotion as well as also normalize the relationship between SLC6A4 methylation and activation patterns in frontal-limbic circuitry. Our results from these three studies strengthen the theory that environmental influences are critical in establishing early vulnerability factors for MDD, driving epigenetic processes, and altering brain processes as an individual undergoes treatment, or experiences relapse.

EXAMINING HOW SAME-GENDER AND MIXED-GENDER COUPLES NAVIGATE SEXUAL ISSUES IN THEIR RELATIONSHIPS

Sexual scripts—the definitions and expectations that individuals hold for sexual interactions—are thought to play an important role in the maintenance of sexual well-being. Sexual scripts can be rigid or flexible, and they can be concordant or discordant between members of a couple. Sex therapists support sexual script flexibility for maintaining sexual and relationship satisfaction when couples are navigating sexual issues. However, empirical research examining the role of sexual script flexibility and the degree of script concordance/discordance in couples’ sexual well-being has been limited, due in part to the limited measures available. Furthermore, within the existing research, there has been an unfortunate tendency to exclude individuals in same-gender relationships – perpetuating the long-standing knowledge gap in the literature on positive sexuality in diverse relationships. To address these gaps in the literature, we conducted a series of online studies that recruited individuals in diverse relationships. A measure of individual sexual script flexibility in response to sexual issues was developed (Chapter 2); in addition, the structure of an existing measure assessing couple sexual scripts in response to a sexual issue was evaluated (Chapter 3). Chapter 4 examined how individuals in diverse relationships compared on measures of individual sexual script flexibility and on couple sexual scripts. Findings suggest that there are more similarities than differences across diverse couples. Chapter 5 explored how flexibility in an individual’s approach to sexual issues relates to sexual well-being, specifically by assessing sexual communication and partner responses as mediators. Results suggest that individual sexual script flexibility relates to sexual well-being through reciprocal partner processes. Collectively, this research program suggests that more similarities than differences exist between individuals in same- and mixed-gender relationships, and that partners are important to consider in the relationship between individual sexual script flexibility and sexual well-being. These findings have implications for sex and couple therapy; these results emphasize the importance of interventions that target both members of the couple, and further our understanding of sexuality in same- and mixed-gender relationships.