Estradiol Is Associated With Altered Cognitive and Physiological Responses During Fear Conditioning and Extinction in Healthy and Spider Phobic Women

The first-line psychological treatment for anxiety disorders is exposure therapy, which can be modeled in the laboratory using fear extinction. In healthy women, estradiol levels predict return of fear following extinction, whereas low levels are associated with greater return of fear. Investigating whether estradiol is similarly associated with extinction in clinically anxious women may provide insight to mechanisms underlying symptom relapse following exposure therapy. In the present study, women with spider phobia and healthy women participated in a 2-day fear conditioning and extinction procedure during a period of high or low estradiol levels. Skin conductance responses, shock expectancy, and valence ratings were measured throughout. Women exhibited comparable decreases in physiological arousal from conditioning to the end of extinction training on Day 1. However, compared to women with high estradiol, and irrespective of clinical status, women with low estradiol exhibited significant return of physiological arousal at extinction recall on Day 2, despite accurate ratings regarding the likelihood of shock. Low estradiol women also reported heightened threat expectancy and physiological responding during presentation of safety cues. These results may point to novel means of enhancing exposure therapy in women by timing treatment delivery during periods of higher estradiol levels.