Brain estrogen and its synthesis has emerged as a robust mediator of sex differences in the expression of a range of specific pathological behaviors, but limited data inform models of brain estrogen in human psychopathology. Bulimia nervosa (BN) is a striking example of the potential role of brain estrogen in the pathogenesis of disturbed feeding behavior (e.g., binge eating, loss of control, food choice) and inhibitory control to emotionally salient stimuli. Variability in this system may explain the elevated prevalence rates of BN among women. There is no direct measure of in vivo brain estrogen availability in humans, but the PET ligand [11C]vorozole provides a unique opportunity to characterize estrogen tone in the brain by measuring the availability of the primary metabolic enzyme involved in estrogen production. Consequently, we propose a study of the availability of brain aromatase in 12 adults (6 men and 6 women) with BN using the novel PET ligand [11C]vorozole and 24 historical age, sex, and body mass index matched healthy controls. The application proposes to: (1) characterize regional differences in aromatase availability among men and women with BN relative to healthy controls, and (2) examine the relationship between brain aromatase as measured by [11C]vorozole and measures of inhibitory control in these participants, and (3) examine correlation between aromatase levels and laboratory binge eating. We hypothesize that men and women with BN will have lower aromatase availability in amygdala in comparison to healthy controls, and that regional aromatase availability will correlate to laboratory measures of impulsivity and symptom expression. Thus, our study will be the first empirical test of the role of a sexually dimorphic brain mechanism (i.e., estrogen biosynthesis) in men and women with BN, and validation of our methodology would allow us to expand this research to test broader sex differences in psychopathology where inhibitory control and impulsivity affects symptom expression and maintenance. Results could lead to a new translational program of research linking brain synthesized sex hormones to psychopathology.
Brain estrogen has emerged as a robust contributor to a range of specific pathological behaviors; however, data on the role of the brain estrogen system in human psychopathology are extremely limited. The proposed study will be the first study to use PET imaging to characterize estrogen biosynthesis in patients with bulimia nervosa and its relationship to impulsivity and symptom expression.
