Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence

Domes, Gregor; Heinrichs, Markus; Gläscher, Jan; Büchel, Christian; Braus, Dieter F.; Herpertz, Sabine C.

doi:10.1016/j.biopsych.2007.03.025

Cited by 689 publications

(603 citation statements)

References 31 publications

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“…In line with our findings, OT administration effects in left amygdala reactivity toward emotional faces have been found in healthy males (Gamer et al, 2010;Kirsch et al, 2005), healthy females (Domes et al, 2010) and male patients with Asperger's syndrome (Domes et al, 2014). On the other hand, OT administration effects on right-sided amygdala reactivity toward emotional faces has also been observed in healthy males (Domes et al, 2007;Petrovic et al, 2008), females with and without BPD (Bertsch et al, 2013) and males with Asperger's syndrome (Domes et al, 2013). Only one study (in male GSAD patients) found OT administration effects on bilateral amygdala reactivity (Labuschagne et al, 2010).…”

Section: Discussionsupporting

confidence: 90%

“…Notably, we found that OT enhanced amygdala reactivity in both male and female trauma-exposed controls. This is in line with previous observations in healthy females, but at odds with previous findings in healthy males, which generally showed dampened amygdala reactivity toward negative stimuli after OT administration (eg, Domes et al, 2007;Kirsch et al, 2005;Petrovic et al, 2008). Our findings underline previous observations that OT administration effects depend on inter-individual factors (eg, psychopathology and/ or trauma exposure).…”

Section: Discussionsupporting

confidence: 89%

“…Notably, we found an overall amygdala enhancing effect, for all emotional faces, which may indicate generally enhanced processing of socially salient environmental cues (ie, salience processing, Seeley et al, 2007). Although OT administration has predominantly been found to dampen amygdala reactivity (eg, Domes et al, 2007;Kirsch et al, 2005;Petrovic et al, 2008), increased amygdala reactivity has also been observed after OT administration. OT administration resulted in enhanced amygdala reactivity toward happy faces in healthy males (Gamer et al, 2010), and toward fearful (Domes et al, 2010) and angry faces (Bertsch et al, 2013) and threatening scenes (Lischke et al, 2012) in healthy females.…”

Section: Discussionmentioning

confidence: 56%

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Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Koch

Zuiden

Nawijn

et al. 2015

Neuropsychopharmacol

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Post-traumatic stress disorder (PTSD) is a disabling psychiatric disorder. As a substantial part of PTSD patients responds poorly to currently available psychotherapies, pharmacological interventions boosting treatment response are needed. Because of its anxiolytic and pro-social properties, the neuropeptide oxytocin (OT) has been proposed as promising strategy for treatment augmentation in PTSD. As a first step to investigate the therapeutic potential of OT in PTSD, we conducted a double-blind, placebo-controlled, cross-over functional MRI study examining OT administration effects (40 IU) on amygdala reactivity toward emotional faces in unmedicated male and female police officers with (n = 37, 21 males) and without (n = 40, 20 males) PTSD. Trauma-exposed controls were matched to PTSD patients based on age, sex, years of service and educational level. Under placebo, the expected valence-dependent amygdala reactivity (ie, greater activity toward fearful-angry faces compared with happy-neutral faces) was absent in PTSD patients. OT administration dampened amygdala reactivity toward all emotional faces in male and female PTSD patients, but enhanced amygdala reactivity in healthy male and female traumaexposed controls, independent of sex and stimulus valence. In PTSD patients, greater anxiety prior to scanning and amygdala reactivity during the placebo session were associated with greater reduction of amygdala reactivity after OT administration. Taken together, our results indicate presumably beneficial neurobiological effects of OT administration in male and female PTSD patients. Future studies should investigate OT administration in clinical settings to fully appreciate its therapeutic potential.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 56%

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Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Koch

Zuiden

Nawijn

et al. 2015

Neuropsychopharmacol

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“…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 (Eckstein and Hurlemann, 2013;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 (Hurlemann and Scheele, 2015;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 and Johansen, 2014).…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Facilitates Pavlovian Fear Learning in Males

Eckstein

Scheele

Patin

et al. 2015

Neuropsychopharmacol

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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.

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“…Many human studies have found a role for oxytocin in social memory and memory for faces (Savaskan et al, 2008;Guastella et al, 2009) but not an increased memory for non-social stimuli (Rimmele et al, 2009) increased trust (Kosfield et al, 2005;Zak et al, 2005;Baumgartner et al, 2008;Petrovic et al, 2008), increased security of attachments and partner support (Grewen et al, 2005;Buchheim et al, 2009), increased empathy (Barraza and Zak, 2009) and increased ability to read the affective state of others (Theory of mind; Domes et al, 2007;Goldman et al, 2008). Oxytocin levels can be observed to change quickly in response to the social environment, including after warm contact between couples (Grewen et al, 2005;Holt-Lunstad et al, 2008) massage (Carter et al, 2007) or maternalinfant bonding (White-Traut et al, 2009).…”

Section: Neuroendocrine Hypothesismentioning

confidence: 99%

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

Aiello

Whitaker‐Azmitia

2011

The Anatomical Record

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The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphicthe amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-b estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Anat Rec, 294:1663-1670, 2011. V V C 2011 Wiley-Liss, Inc.Key words: autism; oxytocin; cortisol; sexual differentiation; extreme male TWO HYPOTHESESSimply stated, the hypothesis which we are proposing in this article, and the work currently ongoing in our lab, is that enhanced sexual differentiation of the brain, towards the male phenotype, leads to changes in the neuroendocrine factors, oxytocin and cortisol. These factors are involved in the processing and evaluation of social bonding experiences and any disruption in their typical function can lead to the primary defining characteristic of the autism phenotype-inadequate social bonding. The Extreme Male Hypothesis of AutismAutism is a disorder of brain development and thus any factors which regulate brain development and are known to be altered in autism should be considered as possibly contributing to the phenotype. For example, much of our previous work and work of others, has focused on the known role of serotonin in brain development as well as the well known hyperserotonemia which occurs in autism (Whitaker-Azmitia, 2005). More recently, researchers have proposed a role for sexual differentiation of the brain in the phenotypic behaviors of

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Oxytocin Attenuates Amygdala Responses to Emotional Faces Regardless of Valence

Cited by 689 publications

References 31 publications

Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Oxytocin Facilitates Pavlovian Fear Learning in Males

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

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