Impact of Early Life Stress and 5-HTTLPR on Adulthood Stress Reactivity: Investigation of Changes in Cortisol, Gene Expression and DNA Methylation

Abstract

Early life stress (ELS) is considered one of the important risk factors for adulthood psychopathology and has been associated with impairments in stress response systems such as the Hypothalamic-Pituitary-Adrenal axis (HPA). Over the last decade, studies on Gene-Environment interactions (GxEs) also suggested moderation of this relationship by genetic factors, such as the serotonin transporter polymorphism (5-HTTLPR). Although there are many studies investigating these associations, the underlying biopsychosocial mechanisms are not yet clear. The aim of this dissertation is to identify some of these mechanisms through the use of intermediate phenotypes such as cortisol reactivity, stress-related gene expression and DNA methylation. Healthy Caucasian men were recruited from the Stony Brook University and surrounding communities for participating in an experimental session that involved completion of questionnaires, a life events interview and an acute psychosocial stress paradigm called the Trier Social Stress Test (TSST). Saliva and blood samples were collected for genotyping, cortisol, gene expression and DNA methylation analyses. Results indicate an interaction between ELS and 5-HTTLPR on cortisol reactivity to the TSST as well as differential expression and DNA methylation of the candidate genes. These results provide evidence for the impact of ELS and 5-HTTLPR on different intermediate phenotypes leading to altered stress reactivity in adulthood. Future studies with different gender, ethnicity and clinical groups would complement the results of this study and open up possibilities for behavioral and pharmacological interventions.