Dissecting the role of estradiol in mediating gender-specific anxiolytic and prosocial effects of oxytocin

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Anxiety disorders are among the most common mental illnesses and a substantial percentage of patients do not benefit from established therapeutic approaches. The neuropeptide oxytocin (OXT) has anxiolytic and prosocial properties and may thus be used as an adjunct to augment existing therapies. However, both the prevalence rates of anxiety disorders and the social effects of OXT substantially vary between women and men. The present project was therefore designed to examine gender-specific effects of OXT in healthy participants and to probe interactions between OXT and the sex steroid estradiol as a potential mechanism mediating sexual dimorphisms. Specifically, in a pharmacological behavioral study, we plan to compare OXT effects on fear extinction and emotion recognition between men and women. In a second study, we will use functional magnetic resonance imaging to explore the interplay of OXT and estradiol on (i) amygdala activation during an emotional face matching task and (ii) reward-associated brain activations in response to interpersonal touch. We hypothesize that administration of exogenous estradiol will boost the anxiolytic and prosocial effects of OXT. Collectively, by shedding light on the neurobiological basis and underlying mechanisms of gender-specific treatments for anxiety disorders, the planned project could have a large translational impact (from bench to bedside). Administration of OXT after estradiol pre-treatment might help enhance the therapeutic efficacy of OXT in future clinical trials.