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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Available from: Alexander Lischke
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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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    ABSTRACT: Attending to and understanding one's own feelings are components of meta-mood and constitute important socio-affective skills across the entire lifespan. Growing evidence suggests a modulatory role of the neuropeptide oxytocin on various socio-affective processes. Going beyond previous work that almost exclusively examined young men and perceptions of emotions in others, the current study investigated effects of intranasal oxytocin on meta-mood in young and older men and women. In a double-blind between-group design, participants were randomly assigned to self-administer either intranasal oxytocin or a placebo before responding to items from the Trait Meta-Mood Scale (TMMS) about attention to feelings and clarity of feelings. In contrast to older women, oxytocin relative to placebo increased attention to feelings in older men. Oxytocin relative to placebo enhanced meta-mood in young female participants but reduced it in older female participants. This pattern of findings supports an age-and sex-differential modulatory function of the neuropeptide oxytocin on meta-mood, possibly associated with neurobiological differences with age and sex.
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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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    ABSTRACT: In human evolution, social group living and Pavlovian fear conditioning have evolved as adaptive mechanisms promoting survival and reproductive success. The evolutionarily conserved hypothalamic peptide oxytocin is a key modulator of human sociality, but its effects on fear conditioning are still elusive. In the present randomized controlled study involving 97 healthy male subjects, we therefore employed functional magnetic resonance imaging and simultaneous skin conductance response (SCR) measures to characterize the modulatory influence of intranasal oxytocin (24 IU) on Pavlovian fear conditioning. We found that the peptide strengthened conditioning on both the behavioral and neural levels. Specifically, subjects exhibited faster task-related responses and enhanced SCRs to fear-associated stimuli in the late phase of conditioning, which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function. This speaks against amygdalocentric views of oxytocin having pure anxiolytic-like effects. Instead, it suggests that the peptide enables extremely rapid and flexible adaptation to fear signals in social contexts, which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma.Neuropsychopharmacology accepted article preview online, 14 August 2015. doi:10.1038/npp.2015.245.
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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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    ABSTRACT: The ability to predict the behavior of others based on their mental states is crucial for social functioning. Previous studies have provided evidence for the role of Oxytocin (OXT) in enhancing the ability to mentalize. It has also been demonstrated that the effect of OXT seems to strongly depend on socio-cognitive skills with more pronounced effects in individuals with lower socio-cognitive skills. Although recent studies indicate that mentalizing is related to empathy, no study has yet examined whether the effects of OXT on mentalizing depend on the ability to empathize. 71 male participants participated in a double-blind, between-subjects, placebo-controlled experiment. The Reading the Mind in the Eye Test (RMET) was used to investigate mentalizing abilities. We analyzed the effect of OXT on easy and difficult items of the RMET depending on differential empathy scores of the participants as assessed with the Empathy Quotient (EQ). Our results showed that OXT improves mentalizing for difficult but not for easy items. We generally observed increased mentalizing accuracy in participants with higher empathy scores. Importantly, however, whereas the performance in participants with higher empathy scores was comparable in both OXT and placebo condition, OXT specifically enhanced mentalizing accuracy in participants with lower empathy scores. Our findings suggest that OXT enhances mentalizing abilities. However, we also demonstrate that not all participants benefited from OXT application. It seems that the effects of OXT strongly depend on baseline social-cognitive skills such as empathy. Copyright © 2015 Elsevier Ltd. All rights reserved.
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