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Cited by 87Neuroendocrine regulation and behaviorMemory and Neural MechanismsStress Responses and Cortisol

Oxytocin Facilitates Pavlovian Fear Learning in Males

Open access
Eckstein, Monika, Scheele, Dirk, Patin, Alexandra, Preckel, Katrin, Becker, Benjamin, Walter, Annika, Domschke, Katharina, Grinevich, Valery +2 more·2016·Neuropsychopharmacology
DOI 10.1038/npp.2015.245PMC PMC4748433
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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.

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Written from the paper’s full text.

TL;DR

In a randomized, double-blind, placebo-controlled fMRI study of 97 healthy males, intranasal oxytocin (24 IU) administered before Pavlovian fear conditioning strengthened conditioning on behavioral, psychophysiological, and neural measures. Oxytocin enhanced responses to fear-associated stimuli via extra-amygdalar cingulate regions while dampening responses to the electric shock, suggesting it facilitates fear learning rather than acting as a pure anxiolytic.

Key findings

  • Oxytocin strengthened behavioral conditioning: faster responses to CS+ than CS− under oxytocin (t(32) = −3.57, P < 0.01, d = −0.15) but not placebo (P = 0.45), with a type × treatment interaction (F(1,90) = 3.13, P = 0.04 one-tailed, η² = 0.03).
  • In the late conditioning phase, skin conductance responses to CS+ were larger under oxytocin (1.09 ± 0.94 mS) than placebo (0.66 ± 0.11 mS; t(16.27) = 1.88, P = 0.038 one-tailed, d = 0.78), while CS− did not differ (P = 0.30); oxytocin also decreased SCRs to the electric shock (0.27 ± 0.74 z vs 0.74 ± 0.69 z; t(95) = −3.14, P < 0.01, d = 0.67).
  • fMRI showed higher right subgenual anterior cingulate cortex activation for CS+ > CS− under oxytocin (peak MNI 3, 29, −2; t(94) = 3.57, P_FWE = 0.03), enhanced left posterior midcingulate cortex activity only for social stimuli (peak MNI −15, −43, 37; t(93) = 3.73, P_FWE = 0.04; social vs non-social t(184) = 3.54, P_FWE = 0.049), and decreased shock-related left pregenual ACC responses (peaks −3, 44, 4, t(94) = 4.09 and −3, 59, 4, t(94) = 3.62, P_FWE = 0.02, k = 77); amygdala ROI analyses were not significant.

Methods

  • Randomized, double-blind, placebo-controlled, parallel-group study in 97 healthy, right-handed adult males (mean age 24.45 ± 4.02 years); participants received intranasal oxytocin (24 IU) or placebo (0.9% sodium chloride) before an fMRI fear-conditioning paradigm.
  • The paradigm used social (face) and non-social (house) CS pairs, with CS+ paired with an aversive electric shock in 70% contingency; conditioning was modeled in early (trials 1–15) and late (trials 16–30) phases.
  • SCR analysis focused on subjects showing successful conditioning, yielding a final SCR sample of 47 subjects (17 oxytocin, 30 placebo); fMRI data were analyzed with a two-level random-effects GLM in SPM8, including ROI analyses for amygdala and cingulate cortex subdivisions with FWE correction.

Limitations

  • Stated: only healthy men were tested, limiting extrapolation to females; no expectancy or probability ratings were obtained; imaging used a 1.5-T scanner, so absent amygdala effects may relate to restricted spatial resolution; SCR results are based on a smaller sample than fMRI results because analysis focused on successfully conditioned subjects.
  • Evident from the text: the final SCR sample (n = 47) was less than half of the randomized sample (n = 97), so psychophysiological conclusions rest on a selected subset.
  • Evident from the text: the study did not find significant amygdala ROI effects, and the authors note this may be due to scanner resolution rather than absence of amygdala involvement.

Model-written summary. Check it against the paper before relying on it.

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Registry

Crossref · 10.1038/npp.2015.245

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 57 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Intranasal oxytocin was paralleled by heightened activity in cingulate cortex subregions.

    “which was paralleled by heightened activity in cingulate cortex subregions in the absence of changes in amygdala function.”
    Quote in the paperSubstantial claim
  • Findingown data

    Intranasal oxytocin (24 IU) strengthened Pavlovian fear conditioning in healthy male subjects, as measured behaviorally and neurally.

    “We found that the peptide strengthened conditioning on both the behavioral and neural levels.”
    • Also stated in: § DISCUSSION · hedged
      “Our findings indicate that OXT IN increases learning performance during conditioning as evident in both reaction times and SCRs.”
    Quote in the paperSubstantial claim
  • Findingown data

    Under intranasal oxytocin, subjects exhibited faster task-related responses to fear-associated stimuli (CS+) than to safety cues (CS-) during conditioning.

    “Post-hoc t-tests revealed faster responses to the CS+ than to the CS-under OXT IN influence (t (32) = -3.57,Po0.01, d = -0.15)but not under PLC (P = 0.45).”
    Quote in the paperSubstantial claim
  • Findingown data

    Under intranasal oxytocin, subjects exhibited enhanced skin conductance responses to fear-associated stimuli (CS+) in the late phase of conditioning.

    “enhanced SCRs to fear-associated stimuli in the late phase of conditioning”
    • Also stated in: § Psychophysiological Results · plain
      “during the late phase the electrodermal response to the CS+ was significantly more pronounced under OXT (Mean ± SD = 1.09 ± 0.94 mS) than under PLC (Mean ± SD = 0.66 ± 0.11 mS) (t (16.27) = 1.88,P = 0.038, onetailed, d = 0.78)”
    Quote in the paperSubstantial claim
  • Findingown data

    Intranasal oxytocin did not change amygdala function.

    “in the absence of changes in amygdala function”
    • Also stated in: § FMRI Results · plain
      “Interestingly, additional ROI analyses of the amygdala did not yield any significant results”
    • Also stated in: § DISCUSSION · plain
      “At the neural level, OXT IN did not affect amygdala function”
    Quote in the paperSubstantial claim
  • May combine two claims. 25
  • Classified as probably not a substantial claim. 38

  • May combine two claims.

    Findingown data

    Under oxytocin, responses to CS+ were faster than to CS-, whereas under placebo there was no significant difference.

    “Post-hoc t-tests revealed faster responses to the CS+ than to the CS-under OXT IN influence (t (32) = -3.57,Po0.01, d = -0.15)but not under PLC (P = 0.45).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was a significant main effect of stimulus type and a significant type × treatment interaction on mean reaction times.

    “The analysis yielded a significant main effect of type (F (1,90) = 7.67, Po0.01, η 2 = 0.08) and an interaction of type and treatment (F (1,90) = 3.13, P = 0.04 one tailed, η 2 = 0.03, cf. Figure 1a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Oxytocin attenuated both neural and psychophysiological responses to the aversive electric shock.

    “Furthermore, in accordance with previous findings (Rash et al, 2014), OXT attenuated both neural and psychophysiological responses to the aversive electric shock.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rash et al, 2014 source

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    Findingown data

    No OXT effect on subcortical structures such as the amygdala was observed.

    “the absence of an OXT effect on subcortical structures such as the amygdala”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The amygdala is central to a distributed neural circuitry orchestrating Pavlovian fear conditioning in humans and other species.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Herry and Johansen, 2014 source

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    Premisecitation

    The hypothalamic peptide oxytocin is a key molecular substrate of social group living and monogamous pair bonds in humans.

    “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)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Scheele et al, 2012 source

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    • cites Scheele et al, 2013 source

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    Premisecitation

    Intranasal oxytocin promotes in-group trust.

    “thereby promoting in-group trust (Kosfeld et al, 2005)”
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    • cites Kosfeld et al, 2005 source

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    Premisecitation

    Intranasal oxytocin promotes cooperation.

    “cooperation (De Dreu et al, 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites De Dreu et al, 2010 source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In a previous study, intranasal oxytocin administered after Pavlovian fear conditioning and before fear extinction facilitated fear extinction and inhibited amygdala response.

    “In a previous study, we found that OXT IN administered following a Pavlovian fear-conditioning paradigm and prior to fear extinction facilitated fear extinction and inhibited amygdala response (Eckstein et al, 2014b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Eckstein et al, 2014b

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    Interpretationreasoning

    Oxytocin's facilitation of adaptation to fear signals may confer evolutionary advantages but could elevate vulnerability for pathological sequelae of interpersonal trauma.

    “which may confer clear evolutionary advantages but could also elevate vulnerability for the pathological sequelae of interpersonal trauma.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intranasal oxytocin promotes affiliative behaviors.

    “affiliative behaviors (Hurlemann and Scheele, 2015;Rilling and Young, 2014)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hurlemann and Scheele, 2015

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    • cites Rilling and Young, 2014 source

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    Premisecitation

    Intranasal oxytocin produces anxiolytic-like effects as a result of dampened amygdala reactivity to threat.

    “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)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Eckstein and Hurlemann, 2013 source

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    • cites Domes et al, 2007 source

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    • cites Lischke et al, 2012 source

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  • Classified as probably not a substantial claim.

    Study design and conductnone given

    SCR analysis was restricted to subjects who displayed successful conditioning (larger SCR to CS+ than CS- in the late conditioning phase).

    “We focused our SCR analysis on the data of subjects who displayed successful conditioning manifest in a larger SCR to the CS+ than to the CSin the late conditioning phase.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Intranasal oxytocin facilitates bodily reactions to and episodic memory for aversive events.

    “further research showing that OXT IN facilitates bodily reactions to and episodic memory for aversive events (Striepens et al, 2012)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Striepens et al, 2012 source

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    Study design and conductreasoning

    A parallel group design was preferred over a cross-over within-subject design to avoid potentially confounding effects of repetitive fear conditioning.

    “We preferred a parallel group design over a cross-over, within-subject design in order to avoid potentially confounding effects of repetitive fear conditioning.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Quality checks were conducted to identify and exclude non-responders and invalid recordings.

    “Quality checks were conducted in order to identify and exclude non-responders and invalid recordings (Eckstein et al, 2014b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Eckstein et al, 2014b

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    According to one model, fear conditioning and extinction are two competing processes, and the stronger process overrides and inhibits the other.

    “According to one model of fear conditioning and extinction as being two competing processes, the stronger of the two processes overrides and thus inhibits the other (Lissek and van Meurs, 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lissek and van Meurs, 2014

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    Premisecitation

    Pavlovian fear conditioning typically accelerates the reaction to the CS+ but not the CS-.

    “Pavlovian fear conditioning typically accelerates the reaction to the CS+ but not the CS- (Critchley et al, 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Critchley et al, 2002 source

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  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Volunteers were randomly assigned to intranasal administration of either oxytocin (24 IU) or placebo in accordance with current guidelines.

    “Volunteers were randomly assigned to intranasal administration of either OXT (24 IU; Syntocinon-Spray, Novartis; three puffs per nostril, each with 4 IU OXT) or PLC (0.9% sodium chloride solution) in accordance with current guidelines (Guastella et al, 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Guastella et al, 2013 source

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    Study design and conductown data

    The experimental groups did not differ in demographic variables or neuropsychological performance.

    “The experimental groups did not differ in demographic variables or neuropsychological performance (cf.Table 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The fMRI fear-conditioning procedure was an adapted version of a validated procedure.

    “We used an adapted version of a validated fMRI fearconditioning procedure (Becker et al, 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Becker et al, 2013

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    Premisecitation

    Intranasal oxytocin increases the perception of social stress in the absence of support.

    “increases the perception of social stress in the absence of support (Eckstein et al, 2014a)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Eckstein et al, 2014a

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    Premisecitation

    Intranasal oxytocin promotes defensive aggression towards competing outgroups.

    “promotes defensive aggression towards competing outgroups (De Dreu et al, 2010)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites De Dreu et al, 2010 source

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    Study design and conductown data

    The treatment groups did not differ in the number of exclusions, and 47 subjects (17 oxytocin, 30 placebo) entered the final analysis.

    “Of note, the treatment groups did not differ in the number of exclusions (χ 2 (1) = 1.33,P = 0.25) and 47 subjects (n = 17 for OXT and n = 30 for PLC) entered the final analysis.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Prevailing pathomechanistic models of anxiety disorders emphasize a key role of Pavlovian fear conditioning in the acquisition of avoidance behavior.

    “Indeed, the prevailing pathomechanistic models of anxiety disorders have emphasized a key role of Pavlovian fear conditioning in the acquisition of avoidance behavior (Lissek et al, 2008;Rauch et al, 2006).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Lissek et al, 2008 source

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    • cites Rauch et al, 2006 source

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    Study design and conductown data

    The study was registered in ClinicalTrials.gov (Identifier: NCT02156661).

    “The study was registered in the ClinicalTrials.govdatabase (Identifier: NCT02156661) provided by the US National Institutes of Health.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Middle and anterior parts of the cingulate cortex are involved in negative affect.

    “which are involved in negative affect (Vogt, 2005)”
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    • cites Vogt, 2005 source

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    Study design and conductown data

    The study used a randomized, placebo-controlled, double-blind, between-subject design.

    “We applied a randomized, placebo-controlled, double-blind, between-subject design.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Fear-related neural networks include the amygdala as well as middle and anterior parts of the cingulate cortex.

    “These networks include the amygdala as well as middle and anterior parts of the cingulate cortex”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sehlmeyer et al, 2009 source

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    Study design and conductreasoning

    Participants completed a baseline skin conductance response measurement and a comprehensive neuropsychological test battery to control for possible pretreatment differences.

    “Participants completed a baseline skin conductance response (SCR) measurement and a comprehensive neuropsychological test battery to control for possible pretreatment differences.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    By increasing the perceived salience of social cues, OXT could optimize the efficiency of fear learning in social settings, thereby increasing the likelihood of avoiding distressing situations in interpersonal relationships.

    “This could illustrate a key evolutionary function of OXT, ie, by increasing the perceived salience of social cues, OXT could optimize the efficiency of fear learning in social settings, thereby increasing the likelihood of avoiding distressing situations in interpersonal relationships.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PTSD affects victims of various types of traumas at differential rates: intentional acts of interpersonal violence, in particular sexual assault, lead to PTSD at far higher rates than do accidents or disasters.

    “intentional acts of interpersonal violence, in particular sexual assault, lead to PTSD at far higher rates than do accidents or disasters (Cantor, 2009).”
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    • cites Cantor, 2009 source

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    Premisecitation

    In patients with social anxiety disorder (SAD), pMCC activation typically occurs in response to threat stimuli.

    “In patients with SAD, which is characterized in part by an increased sensitivity to social signals, pMCC activation typically occurs in response to threat stimuli (Gaebler et al, 2014)”
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    • cites Gaebler et al, 2014 source

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    Premisecitation

    The subgenual ACC is especially involved in fear responses and shows abnormal activity in mood disorders.

    “which is especially involved in fear responses and shows abnormal activity in mood disorders (Drevets et al, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Drevets et al, 2008 source

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    Premisecitation

    Findings in mice suggest that OXT specifically facilitates social fear conditioning.

    “findings in mice suggesting that OXT specifically facilitates social fear conditioning (Zoicas et al, 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zoicas et al, 2014 source

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  • May combine two claims.

    Interpretationreasoning

    OXT IN not only enhances preexisting activations but also alters the underlying neural circuitry of fear conditioning.

    “OXT IN therefore seems not only to enhance preexisting activations but also to alter the underlying neural circuitry of fear conditioning.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Increased vigilance or defense typically characterizes SAD and PTSD.

    “This increased vigilance or defense typically characterizes SAD (Heeren et al, 2015) and PTSD (Cantor, 2009).”
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    • cites Heeren et al, 2015 source

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    • cites Cantor, 2009 source

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    Interpretationown data

    Oxytocin not only facilitated behavioral indices of fear conditioning but also enhanced activity in brain regions implicated in this paradigm.

    “Thus OXT not only facilitated behavioral indices of fear conditioning but also enhanced activity in brain regions implicated in this paradigm.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The pMCC has a hypothesized role in orienting the body toward innocuous and noxious somatosensory stimuli.

    “the hypothesized role of this region in 'orienting the body toward innocuous and noxious somatosensory stimuli' (Vogt, 2005).”
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    • cites Vogt, 2005 source

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    Premisecitation

    The anterior cingulate cortex (ACC) has a crucial role within a general neural fear circuit and within Pavlovian fear conditioning.

    “previous findings showing that the ACC has a crucial role within a general neural fear circuit (Hariri et al, 2003) as well as within the framework of Pavlovian fear conditioning (see reviews by Milad et al, 2007;Sehlmeyer et al, 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Hariri et al, 2003 source

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    • cites Milad et al, 2007 source

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    • cites Sehlmeyer et al, 2009 source

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    Interpretationcitation

    An oxytocin-induced augmentation of fear conditioning cannot be attributed to increased pain responses but appears to be mediated by improved learning.

    “Thus an OXT-induced augmentation of fear conditioning cannot be attributed to increased pain responses but appears to be mediated by improved learning (Hurlemann et al, 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hurlemann et al, 2010 source

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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    The study presents an evolutionary model of OXT as the basis of increased adaptation to dynamic social contexts and poses that the cost of this increase is a higher susceptibility to social trauma.

    “We present an evolutionary model of OXT as the basis of increased adaptation to dynamic social contexts and pose that the cost of this increase is a higher susceptibility to social trauma.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: SAD and PTSD are based on a fear-conditioning pathomechanism.
    • Rests on an assumption: There has been no data-driven explanation for why PTSD affects victims of different trauma types at differential rates.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study did not obtain expectancy or probability ratings as subtle measures of conditioning.

    “Second, we did not obtain expectancy or probability ratings as subtle measures of conditioning.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some research indicates that OXT could be influential in the treatment of established SAD and PTSD.

    “Some research indicates that OXT could be influential in the treatment of established SAD (Labuschagne et al, 2010) and PTSD (Olff et al, 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Labuschagne et al, 2010 source

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    • cites Olff et al, 2014 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    SCR analysis focused on data of subjects whose SCRs indicated successful conditioning, so SCR results are based on a smaller sample size than fMRI results.

    “Fourth, we focused our SCR analysis on the data of subjects whose SCRs indicated successful conditioning and our SCR results are therefore based on a smaller sample size than our fMRI results (cf.Supplementary Results).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Previous findings indicate a potential benefit of OXT via accelerated fear extinction, implicating OXT as a potential augmentation strategy in medication-enhanced cognitive-behavioral therapy of anxiety disorders.

    “Our previous findings also indicate a potential benefit via accelerated fear extinction, thus implicating OXT as a potential augmentation strategy in medication-enhanced cognitive-behavioral therapy of anxiety disorders (Eckstein et al, 2014b).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Eckstein et al, 2014b

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Whereas men are more likely to experience trauma overall, women experience more interpersonal violence, such as rape.

    “whereas men are more likely to experience trauma overall, women experience more interpersonal violence, such as rape (Kessler et al, 1995).”
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    • cites Kessler et al, 1995 source

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    Premisecitation

    Dysfunction of the ACC is implicated in the development of PTSD.

    “findings implicating dysfunction of the ACC in the development of PTSD (Bremner et al, 2005;Hamner et al, 1999;Shin et al, 2005).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bremner et al, 2005 source

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    • cites Hamner et al, 1999

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    • cites Shin et al, 2005 source

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  • May combine two claims.

    Study design and conductcitation

    The study tested only healthy men, and extrapolation to females is hampered given gender-dimorphic effects of OXT and fear circuits.

    “First, we have only tested healthy men, and given the gender-dimorphic effects of OXT and fear circuits, the extrapolation to females is hampered (Preckel et al, 2014;Scheele et al, 2014b).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Preckel et al, 2014 source

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    • cites Scheele et al, 2014b

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Imaging data were acquired on a 1.5-T scanner, and the absence of an OXT effect on subcortical structures such as the amygdala might be related to the restricted spatial resolution of the scanner.

    “Third, imaging data were acquired on a 1.5-T scanner and thus the absence of an OXT effect on subcortical structures such as the amygdala might be related to the restricted spatial resolution of the scanner.”
    Quote in the paperNot a substantial claim
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  • The paper relies on this without support.

    Pavlovian fear conditioning is an established model for mimicking the psychopathology of patients with social anxiety disorder or posttraumatic stress disorder.

    “Fear conditioning is an established model for mimicking the psychopathology of patients with SAD or PTSD.”

  • The paper relies on this without support.

    SAD and PTSD are based on a fear-conditioning pathomechanism.

    “It is widely accepted that both disorders are based on a fear-conditioning pathomechanism.”

  • The paper relies on this without support.

    There has been no data-driven explanation for why PTSD affects victims of different trauma types at differential rates.

    “As of yet, however, there has been no data-driven explanation as to why PTSD affects victims of various types of traumas at differential rates”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Three studies investigated the effects of oxytocin on startle response to learned threat cues after conditioning and on learned threat following extinction.

    “Three studies investigated the effects of oxytocin on startle response to learned threat cues after conditioning and on learned threat following extinction (Acheson et al., 2013;Eckstein et al., 2015;Eckstein et al., 2016).”

    From Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans (2018) · cites this paper as Eckstein et al., 2016

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Not confirmedt(16.27) = 1.88reported p = .038 · recomputed p = .078

    “t (16.27) = 1.88,p = .038”

  • ConsistentF(1, 90) = 3.13reported p = .04 · recomputed p = .080

    “F (1,90) = 3.13, p = .04”

    The paper states a one-tailed test

  • ConsistentF(1, 45) = 6.31reported p = .02 · recomputed p = .016

    “F (1,45) = 6.31,p = .02”

  • ConsistentF(1, 45) = 4.89reported p = .03 · recomputed p = .032

    “F (1,45) = 4.89, p = .03”

  • ConsistentF(1, 45) = 4.91reported p = .03 · recomputed p = .032

    “F (1,45) = 4.91, p = .03”

  • ConsistentF(1, 45) = 6.2reported p = .02 · recomputed p = .017

    “F (1,45) = 6.20,p = .02”

6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Eckstein, M., Scheele, D., Patin, A., Preckel, K., Becker, B., Walter, A., Domschke, K., Grinevich, V., Maier, W., & Hurlemann, R.
Affiliations
  • University of Bonn (DE)
  • University of Würzburg (DE)
  • German Cancer Research Center (DE)
Corresponding author
Hurlemann, René
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2015-08-14
Volume
41
Issue
4
Pages
932-939
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2015.245
PMC
PMC4748433
OpenAlex
W1185634228
Semantic Scholar
a1fdd51fd4485929ad61aaaf570dc25501600a3c
Cited by
87
References
53
Citations by year
2026: 7 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 13 · 2020: 6 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 6 · 2015: 2
FWCI
15.27
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DZNE Pub (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft (TRR‐58, Project C02, SFB1134, SFB TRR 58)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
oxytocin, fear conditioning, intranasal administration, cingulate cortex, amygdala, skin conductance response, social behavior, interpersonal trauma, evolutionary psychology
MeSH terms
Administration, Intranasal, Adult, Brain Mapping, Conditioning, Classical, Double-Blind Method, Fear, Galvanic Skin Response, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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