Opposite effects of noradrenergic arousal on amygdala processing of fearful faces in men and women

Fear-related disorders are significantly more prevalent in women than in men. Stress may modulate the neurocircuitry of fear and is a critical factor in the pathogenesis of fear-related disorders. Therefore, we tested in the present experiment the hypothesis that noradrenaline and glucocorticoids, two major stress mediators, have differential effects on fear processing in men and women. In a placebo-controlled, double-blind between-subject design, 80 healthy men and women were administered orally the α2-adrenoceptor antagonist yohimbine and/or the synthetic glucocorticoid hydrocortisone before they rated images of neutral and fearful faces with respect to the degree of fearfulness of the facial expression. During presentation of facial expressions, functional magnetic resonance images were collected. Yohimbine increased subjective ratings of the fearfulness of the faces in women but reduced fearfulness ratings in men. Neuroimaging data showed that yohimbine increased amygdala activity in response to fearful faces in women, whereas it attenuated amygdala responsivity to fearful faces in men. Moreover, yohimbine decreased orbitofrontal activity while viewing fearful faces in women. Hydrocortisone did not affect fear processing, neither in men nor in women. Our findings suggest that noradrenergic arousal may have opposite effects on fear processing in men and women. These sex differences may represent a biological mechanism that contributes to the differential prevalence of fear-related disorders in men and women.