Oxytocin increases amygdala reactivity to threatening scenes in females

Department of General Psychiatry, University of Heidelberg, D-69115 Heidelberg, Germany.
Psychoneuroendocrinology (Impact Factor: 4.94). 02/2012; 37(9):1431-8. DOI: 10.1016/j.psyneuen.2012.01.011
Source: PubMed


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.

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    • "ageandsexdifferencesinneuroendocrinefactors(e.g., associatedwithendogenouscentraland/orperipheraloxytocin levels,orneurotransmitterslevelssuchasdopamine),in interactionwithdifferencesingonadalhormones(e.g.,estradiol, testosterone),influencemalleability(suchasviaexogenous oxytocinadministration)ofneuralconnectednessbetween subcorticalandcorticalbrainstructures,whichmayunderlieageby-sexvariationsinoxytocin'ssocio-affectiveeffects.Also,while ourunderstandingofoxytocinreceptorexpressionisnascent, itispossiblethatage-andsex-relatedalterationsonoxytocin receptorexpressioncontributetotheeffectsobservedinour study.Ithasbeenshownthatestrogenupregulatesoxytocin productionandoxytocinreceptorexpressivity(BaleandDorsa, 1997;Vasudevanetal.,2001)inthehypothalamusandother limbicbrainregions.Thiscombinedwithreducedreleaseof androgensinoldercomparedtoyoungmalesmaycontribute toa''rampingup''effectofoldermen'ssocialandaffective systemafterexogenouselevationofoxytocinlevelsviaintranasal administration,andmaycontributetooldermales'greater attentiontotheirownfeelingsintheoxytocincomparedto theplacebogroup.Ofnote,thepresentstudydidnotdirectly controlfortheinfluenceoflevelsofgonadalhormoneson thereportedeffects(Domesetal.,2010;Lischkeetal.,2012). However,theobservedpatternoffindingsremainedaftercontrol forself-reporteduseofhormonereplacementtherapy,useoforal contraceptives,andmenstrualcycle.Futurestudies,thatcollect hormonedatalevelsinadditiontoneuropeptidelevelsanduse brainimagingwhilemenandwomenofdifferentagesattend totheirownfeelingsandprocessemotionalinformation,will havetoconfirmpossibleinteractiveeffectsofhormonesand neuropeptidesonbrainfunctionandbehavior. "
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    • "Key among the molecular substrates of social group living and monogamous pair bonds in humans is the hypothalamic peptide oxytocin (OXT) (Scheele et al, 2012; Scheele et al, 2013). Studies of intranasally delivered exogenous OXT (OXT IN ) have shown that the peptide produces anxiolytic-like effects as a result of dampened amygdala reactivity to threat (Domes et al, 2007, but see Lischke et al, 2012), thereby promoting in-group trust (Kosfeld et al, 2005), cooperation (De Dreu et al, 2010) and affiliative behaviors (Rilling and Young, 2014). The amygdala – an ensemble of functionally distinct nuclei located in the medial temporal lobe – is central to a distributed neural circuitry orchestrating Pavlovian fear conditioning in humans and other species, underscoring its crucial role in promoting reproductive fitness (Herry et al, 2014). "
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    • "SD = 4.8) participated in the study. Only male participants were included because previous studies have reported inconsistent gender effects following OXT application (Domes et al., 2010; Kubzansky et al., 2012; Lischke et al., 2012b). For this reason, we investigated only male subjects in the current study, in hopes of probing the effect of OXT in a more homogeneous sample. "
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