Women and fear regulation: The role of the sex hormone estradiol.

Women are twice as likely as men to develop an anxiety disorder. It is possible that fluctuations in ovarian hormones may contribute to this imbalance, by influencing emotional processes such as fear regulation. Evidence suggests that low estradiol in females is associated with impaired fear extinction, a laboratory analogue of exposure therapy for anxiety disorders. However, studies to date have used basic fear extinction procedures, and the translation of this work to more clinically relevant tasks is yet to be made. Moreover, human studies have primarily measured physiological outcomes such as skin conductance, which, unlike self-report measures, are never used in clinical settings. This thesis aimed to expand the current pre-clinical knowledge regarding estradiol and fear regulation by using experimental parameters with robust links to the development and treatment of anxiety disorders. Additionally, the relationship between estradiol and multiple components of the fear response were examined, including physiology, self-report, and behaviour.Experiment 1 focused on fear extinction, using evolutionarily-relevant stimuli and measuring associations between estradiol, skin conductance, and declarative knowledge. Experiment 2 examined whether estradiol was related to skin conductance and self-reported fear during an impromptu speech task that is commonly used in exposure therapy for social anxiety disorder. Experiment 3 extended the findings of Experiment 2 by specifically examining avoidance behaviour. Experiment 4 investigated whether cognitive restructuring, a therapy-based fear regulation skill, could reduce the estradiol-related differences in skin conductance observed during the speech task, and whether this reduction was differentially linked to estradiol.The current thesis found evidence for a relationship between estradiol and skin conductance across several fear-related tasks. However, no support was found for a relationship between estradiol and other components of the fear response, including self-report and avoidance. These findings are discussed in relation to models of emotion, and with regards to the clinical implications of estradiol-related dissociations within the fear response. It is hoped that this thesis will inspire further pre-clinical research aimed at clarifying the mechanisms underlying hormonal regulation of the fear network, with a view to eventually improving the prognosis and treatment for women with anxiety disorders