اکسی توسین واکنش پذیری آمیگدال برای صحنه های تهدید در زنان را افزایش می دهد

Summary The neuropeptide oxytocin (OT) is well known for its profound effects on social behavior, which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli. In humans, OT decreases amygdala reactivity to threatening faces in males, but enhances amygdala reactivity to similar faces in females, suggesting sex-specific differences in OT-dependent threat-processing. To further explore whether OT generally enhances amygdala-dependent threat-processing in females, we used functional magnetic resonance imaging (fMRI) in a randomized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo. Participants’ eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features. Although OT had no effect on participants’ gazing behavior, it increased amygdala reactivity to scenes depicting social and non-social threat. In females, OT may, thus, enhance the detection of threatening stimuli in the environment, potentially by interacting with gonadal steroids, such as progesterone and estrogen.

. Introduction The neuropeptide oxytocin (OT) is crucially involved in the regulation of reproductive and social behavior in non-human mammals (Lee et al., 2009), including parturition, lactation, parental care, play, bonding and mating. OT also appears to be a potent modulator of human social behavior (Meyer-Lindenberg et al., 2011). In humans, OT attenuates anxiety and stress (Ditzen et al., 2009 and Heinrichs et al., 2003), promotes trust (Kosfeld et al., 2005) and facilitates the encoding (Guastella et al., 2008 and Rimmele et al., 2009) and recognition of facial expressions (Di Simplicio et al., 2009, Domes et al., 2007b, Fischer-Shofty et al., 2010, Lischke et al., 2011, Marsh et al., 2010 and Schulze et al., 2011). With regard to the neurobiological mechanism mediating the behavioral effects of OT, the amygdala with its cortical and subcortical projections appears to be a key region (Pittman and Spencer, 2005). OT is released within the rat amygdala (Bosch et al., 2005 and Ebner et al., 2005), where it acts on specific receptors (Huber et al., 2005 and Terenzi and Ingram, 2005) to modulate fear (McCarthy et al., 1996) and aggression (Bosch et al., 2005). Recent evidence suggests that OT modulates neuronal activity in the human amygdala in a similar way, especially in response to threatening stimuli (Baumgartner et al., 2008, Domes et al., 2007a, Domes et al., 2010a, Gamer et al., 2010, Kirsch et al., 2005, Petrovic et al., 2008 and Singer et al., 2008). Interestingly, OT decreases amygdala reactivity to aversive, threat-related scenes (Kirsch et al., 2005) and fearful, threat-related faces (Domes et al., 2007a, Gamer et al., 2010, Kirsch et al., 2005 and Petrovic et al., 2008) in males, but increases amygdala reactivity to similar faces in females (Domes et al., 2010a). Although sex differences in neuropeptidergic functioning are well known in non-human mammals (Carter et al., 2009), they have rarely been studied in humans. In fact, our initial finding of enhanced amygdala reactivity to fearful faces in females receiving OT has not been replicated yet (Domes et al., 2010a). In addition, it remains unresolved whether the observed OT effects are specific to facial stimuli or generalize to other stimulus classes such as more complex emotional scenes. In consideration of this, the current study examined how OT modulates amygdala reactivity to negative, positive and neutral scenes in females. We also measured how OT affects visual exploration of these scenes because it has been shown that OT alters visual processing of emotional stimuli in males (Gamer et al., 2010). Based on our previous findings (Domes et al., 2010a), we hypothesized that OT specifically enhances amygdala activity to negative scenes, potentially by increasing exploration of salient scene features.

Conclusion Taken together, the findings of the present study, which are consistent with previous ones (Domes et al., 2010a), suggest that OT promotes female threat-detection by increasing amygdala-dependent processing of threat-related stimuli. In males, on the contrary, OT appears to attenuate threat-sensitivity by decreasing amygdala reactivity to threat-related stimuli, particularly to those depicting social threat (Domes et al., 2007a, Gamer et al., 2010, Kirsch et al., 2005 and Petrovic et al., 2008). However, these conclusions should be drawn with caution, considering that we only investigated a relatively small number of females during the mid-luteal phase. Besides this, we were unable to test whether social and non-social scenes differentially affected amygdala-dependent threat-processing. Moreover, we only focused on the processing of threat-related stimuli and did not consider the processing of other aversive stimuli, which may also be affected by OT (Riem et al., 2011). We suggest that future studies should be explicitly designed to investigate amygdala-dependent emotion processing in males and females after OT administration, preferably by explicitly considering cyclic variations in gonadal steroid levels. It, thus, remains an interesting question for future research to determine whether sex-specific differences in neuropeptidergic functioning during the processing of emotional, especially threatening, stimuli are indeed mediated by gonadal steroids (Carter et al., 2009).