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Cited by 98Posttraumatic Stress Disorder ResearchNeuroendocrine regulation and behaviorNeuropeptides and Animal Physiology

Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients

Open access
Koch, Saskia BJ, van Zuiden, Mirjam, Nawijn, Laura, Frijling, Jessie L, Veltman, Dick J, Olff, Miranda·2016·Neuropsychopharmacology
DOI 10.1038/npp.2015.299PMC PMC4832009
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Abstract

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 trauma-exposed 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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a double-blind, placebo-controlled crossover fMRI study, intranasal oxytocin (40 IU) dampened left amygdala reactivity toward emotional faces in male and female PTSD patients but enhanced it in trauma-exposed controls. The dampening effect was strongest in PTSD patients with higher pre-scan anxiety and higher placebo-session amygdala reactivity.

Key findings

  • Under placebo, trauma-exposed controls showed greater left amygdala reactivity to fearful-angry versus happy-neutral faces (P_FWE < 0.001), whereas this valence-dependent pattern was absent in PTSD patients (P_FWE = 0.359).
  • Oxytocin administration produced a significant group-by-medication interaction in the left amygdala (P_FWE = 0.047): it dampened left amygdala reactivity in PTSD patients (P_FWE = 0.034) and enhanced it in trauma-exposed controls (P_FWE = 0.016), independent of sex and stimulus valence.
  • In PTSD patients, higher state anxiety before placebo was positively related to left amygdala reactivity under placebo (r = 0.393, p = 0.021), and greater placebo-session amygdala reactivity mediated greater oxytocin-related dampening (indirect effect 95% CI = 0.0018–0.0248).
  • No significant associations were found between left amygdala reactivity and CAPS total score or subscales (all p > 0.05).

Methods

  • Randomized, double-blind, placebo-controlled, crossover fMRI study of intranasal oxytocin (40 IU Syntocinon) versus saline in unmedicated male and female police officers with PTSD and trauma-exposed controls matched on age, sex, years of service, and education.
  • The abstract reports n = 37 PTSD patients (21 males) and n = 40 trauma-exposed controls (20 males); after exclusions for scanner artifacts and signal dropout, 36 PTSD patients (21 males) and 37 controls (18 males) were analyzed, and correlation analyses used 35 PTSD patients after excluding one female outlier.
  • Participants completed an emotional face-matching task with fearful-angry and happy-neutral faces versus a visuomotor control condition, scanned on average 44.68 ± 3.74 minutes after spray; fMRI analysis used SPM8 with bilateral amygdala ROIs, FWE small-volume correction, and second-level ANOVA with task condition and medication as within-subject factors and group and sex as between-subject factors.

Limitations

  • The paper states that females using oral contraceptives were included, menstrual cycle phase was not standardized, and the trauma-exposed police control sample limits generalizability.
  • The paper notes that oxytocin effects were lateralized to the left amygdala, with the same directionality but non-significant effects in the right amygdala.
  • Evident from the text: the study examined acute neurobiological effects only, not clinical treatment outcomes, and the authors suggest future clinical studies are needed before routine application.

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

Integrity signals

Registry

Crossref · 10.1038/npp.2015.299

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

5 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 46 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    OT administration enhanced amygdala reactivity in healthy male and female trauma-exposed controls.

    “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.”
    Quote in the paperSubstantial claim
  • Findingown data

    Under placebo, trauma-exposed controls showed greater left amygdala reactivity toward fearful-angry faces compared with happy-neutral faces.

    “Post hoc t-tests showed that left amygdala was significantly more activated in traumaexposed controls in response to fearful-angry faces compared with happy-neutral faces (P FWE o0.001).”
    Quote in the paperSubstantial claim
  • Findingown data

    In PTSD patients, right amygdala activity was significantly higher during fearful-angry compared with happy-neutral faces under placebo.

    “Right amygdala activity was significantly higher during fearful-angry compared with happy-neutral faces both in trauma-exposed controls (P FWE o0.001) and PTSD patients (P FWE = 0.005).”
    Quote in the paperSubstantial claim
  • Findingown data

    In PTSD patients, the difference in left amygdala contrast estimates between OT and placebo was trend-significantly positively related to state anxiety prior to placebo administration.

    “In addition, the difference in contrast estimates between OT and placebo administration was trend significant positively related to state anxiety prior to placebo administration (r = 0.298, p = 0.089, Figure 3).”
    Quote in the paperNot a substantial claim
  • Findingown data

    No significant associations between left amygdala reactivity toward emotional faces and CAPS total score or subscales were found.

    “No significant associations between left amygdala reactivity toward emotional faces and CAPS total score or subscales were found (all p40.05).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 26

  • May combine two claims.

    Findingown data

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In PTSD patients, the association between state anxiety and left amygdala reactivity under placebo was significant for happy-neutral faces but not for fearful-angry faces.

    “The association between state anxiety and left amygdala reactivity was significant for reactivity toward happy-neutral faces (r = 0.412, p = 0.014), but not for reactivity toward fearful-angry faces (r = 0.274, p = 0.117).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The effects of OT on amygdala reactivity were independent of sex and stimulus valence.

    “These effects of OT were independent of sex and stimulus valence (all P FWE 40.05).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    OT administration effects on amygdala reactivity were lateralized to the left amygdala, with the same non-significant directionality in the right amygdala.

    “Notably, OT administration effects were lateralized to the left amygdala, although the same (albeit non-significant) directionality of effects was observed in the right amygdala.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    OT administration had opposite effects on amygdala reactivity in PTSD patients versus trauma-exposed controls: dampening in PTSD patients and enhancing in controls.

    “Notably, we found opposite OT administration effects on amygdala reactivity in PTSD patients versus trauma-exposed controls (ie, dampening versus enhancing effects).”
    • Also stated in: § FUNDING AND DISCLOSURE · plain
      “OT administration resulted in dampened amygdala reactivity in PTSD patients and in enhanced amygdala reactivity in trauma-exposed controls.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under placebo, trauma-exposed controls showed differential activation toward fearful-angry faces compared with happy-neutral faces, whereas this effect was absent in PTSD patients.

    “Under placebo, trauma-exposed controls showed differential activation toward fearful-angry faces compared with happy-neutral faces, whereas this effect was absent in PTSD patients.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The study was a randomized, double-blind, placebo-controlled, crossover fMRI study.

    “This randomized, double-blind, placebo-controlled, crossover study consisted of three appointments: one intake session (T0) and two fMRI sessions (T1 and T2).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Oxytocin has pro-social properties.

    “As the neuropeptide oxytocin (OT) has both anxiolytic (Heinrichs et al, 2003) and pro-social (Olff, 2012) properties”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Olff, 2012

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxytocin has been suggested as a promising pharmacological agent to enhance treatment response in PTSD.

    “OT has been suggested as a promising pharmacological agent to enhance treatment response in PTSD (Koch et al, 2014;Olff et al, 2010).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Koch et al, 2014 source

      Not checked in the free run.

    • cites Olff et al, 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    OT may have anxiolytic properties, possibly by inhibiting fear-associated output of the central amygdala to the brainstem and hypothalamus.

    “Our findings extend accumulating evidence that OT may have anxiolytic properties, possibly by inhibiting fear-associated output of the central amygdala to the brainstem and hypothalamus (Huber et al, 2005).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Huber et al, 2005 source

      Not checked in the free run.

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

    Study design and conductnone given

    Medication order was counterbalanced between sessions.

    “Medication order was counterbalanced between sessions.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Amygdala hyperactivity in PTSD may only become apparent during presentation of trauma-related stimuli and not during processing of non-trauma-related stimuli.

    “Alternatively, amygdala hyperactivity in PTSD may only become apparent during presentation of trauma-related stimuli and not during processing of non-trauma-related stimuli (van Rooij et al, 2014), such as the emotional faces used in the present study.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites van Rooij et al, 2014 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Trauma-exposed controls were matched to PTSD patients based on age, sex, years of service, and educational level.

    “Trauma-exposed male (n = 20) and female (n = 20) police officers were recruited via advertisements on websites and in journals of the Dutch police force and were matched to PTSD patients based on age, sex, number of years of service, and educational level.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Strength of therapeutic alliance is an important and consistent predictor of treatment success.

    “Strength of therapeutic alliance, defined as the affective bond between the therapist and patient, is an important and consistent predictor of treatment success (Ormhaug et al, 2014)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ormhaug et al, 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OT has been found to increase in-group trust, pro-social behavior and neural reward sensitivity to social stimuli in men and women.

    “OT has been found to increase in-group trust, pro-social behavior and neural reward sensitivity to social stimuli in men and women (eg, Groppe et al, 2013;Van IJzendoorn and Bakermans-Kranenburg, 2012;Preckel et al, 2014;Striepens et al, 2014).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Groppe et al, 2013 source

      Not checked in the free run.

    • cites Van IJzendoorn and Bakermans-Kranenburg, 2012 source

      Not checked in the free run.

    • cites Preckel et al, 2014 source

      Not checked in the free run.

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

    Premisecitation

    Greater amygdala reactivity during extinction learning in PTSD patients has been associated with impaired extinction recall the next day.

    “Notably, greater amygdala reactivity during extinction learning in PTSD patients has been associated with impaired extinction recall the next day (Milad et al, 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Milad et al, 2009 source

      Not checked in the free run.

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

    Premisecitation

    OT administration resulted in decreased subjective anxiety during a public speaking stressor in healthy individuals.

    “Behaviorally, OT administration resulted in decreased subjective anxiety during a public speaking stressor in healthy individuals (de Oliveira et al, 2012) and increased (recall of) extinction learning in both rodents (Zoicas et al, 2014) and healthy males (Acheson et al, 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites de Oliveira et al, 2012 source

      Not checked in the free run.

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

    Premisecitation

    Therapeutic alliance depends on the patient's attachment security: more secure attachment is related to stronger therapeutic alliance and vice-versa.

    “and depends on the patient's attachment security: more secure attachment is related to stronger therapeutic alliance and vice-versa (see Diener and Monroe, 2011 for a metaanalysis).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Diener and Monroe, 2011 source

      Not checked in the free run.

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

    Premisecitation

    OT administration dampened amygdala reactivity toward emotional stimuli in healthy males, males with GSAD, and females with BPD, although findings for females have been mixed.

    “In addition, functional MRI (fMRI) studies have shown that OT administration dampened amygdala reactivity toward emotional stimuli in healthy males (Kirsch et al, 2005), males with generalized social anxiety disorder (GSAD; Labuschagne et al, 2010) and females with borderline personality disorder (BPD; Bertsch et al, 2013), although findings for females have been mixed (Domes et al, 2010).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Kirsch et al, 2005 source

      Not checked in the free run.

    • cites Labuschagne et al, 2010 source

      Not checked in the free run.

    • cites Bertsch et al, 2013 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    By dampening excessive fear processing during exposure-based therapies, OT administration could result in enhanced treatment response.

    “By dampening excessive fear processing during exposure-based therapies, OT administration could result in enhanced treatment response.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: PTSD patients may benefit from improved fear regulation.

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

    Interpretationcitation

    OT could potentially enhance motivation for treatment, as well as the therapeutic alliance.

    “This way, OT could potentially enhance motivation for treatment, as well as the therapeutic alliance (Olff et al, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Olff et al, 2010 source

      Not checked in the free run.

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

    Premisecitation

    OT administration resulted in increased resting-state functional connectivity between the amygdala and vmPFC in healthy males and in patients with GSAD.

    “Furthermore, OT administration resulted in increased resting-state functional connectivity between the amygdala and vmPFC in healthy males (Sripada et al, 2013) and in patients with GSAD (Dodhia et al, 2014), possibly enhancing top-down control over the fear response.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Sripada et al, 2013 source

      Not checked in the free run.

    • cites Dodhia et al, 2014 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    PTSD patients may be less sensitive to OT administration, owing to alterations at the level of AVP and/or OT receptors, and therefore show dampened amygdala reactivity upon administration of this relatively high dose.

    “PTSD patients, on the other hand, may be less sensitive to OT administration, owing to alterations at the level of AVP and/ or OT receptors, and therefore show dampened amygdala reactivity upon administration of this relatively high dose.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: PTSD patients may benefit from improved fear regulation.

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

    Premisecitation

    A previous study showed elevated amygdala responses towards neutral pictures in PTSD patients compared with trauma-exposed controls.

    “Indeed, a previous study showed elevated amygdala responses towards neutral pictures in PTSD patients compared with trauma-exposed controls (Brunetti et al, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Brunetti et al, 2010 source

      Not checked in the free run.

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

    Premisecitation

    OT administration increased (recall of) extinction learning in rodents and healthy males.

    “Behaviorally, OT administration resulted in decreased subjective anxiety during a public speaking stressor in healthy individuals (de Oliveira et al, 2012) and increased (recall of) extinction learning in both rodents (Zoicas et al, 2014) and healthy males (Acheson et al, 2013).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Zoicas et al, 2014 source

      Not checked in the free run.

    • cites Acheson et al, 2013 source

      Not checked in the free run.

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

    Premisecitation

    Effective exposure therapy was associated with decreased amygdala and enhanced vmPFC activity toward emotional faces over the course of treatment.

    “In addition, effective exposure therapy was associated with decreased amygdala and enhanced vmPFC activity toward emotional faces over the course of treatment (Felmingham et al, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Felmingham et al, 2010 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The prevailing neurocircuitry model of PTSD postulates amygdala hyperactivity and vmPFC hypoactivity toward both trauma-related and non-trauma-related stimuli.

    “The prevailing neurocircuitry model of PTSD postulates amygdala hyperactivity and ventromedial prefrontal cortex (vmPFC) hypoactivity toward both trauma-related and non-trauma-related stimuli (Pitman et al, 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pitman et al, 2012 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In healthy individuals, OT effects seem to follow an inverted u-shape, with doses around 24 IU resulting in more anxiolytic effects than higher doses.

    “In healthy individuals, OT effects seem to follow an inverted u-shape (Rilling et al, 2014), with doses ~24 IU, resulting in more anxiolytic effects than higher doses of OT (Cardoso et al, 2013).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rilling et al, 2014 source

      Not checked in the free run.

    • cites Cardoso et al, 2013 source

      Not checked in the free run.

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

    Interpretationreasoning

    PTSD patients may be specifically sensitive to show greater amygdala responsiveness to the neutral, socially ambiguous faces in the happy-neutral condition.

    “Possibly, PTSD patients may be specifically sensitive to show greater amygdala responsiveness to the neutral, socially ambiguous faces in the happy-neutral condition.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Insecure attachment has been associated with higher PTSD symptom severity in trauma-exposed individuals.

    “Attachment style may be particularly relevant in PTSD: insecure attachment, has been associated with higher PTSD symptom severity in trauma-exposed individuals (see Woodhouse et al, 2015 a meta-analysis).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Woodhouse et al, 2015 source

      Not checked in the free run.

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

    Study design and conductnone given

    The study included females using oral contraceptives.

    “First, we included females using oral contraceptives.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    To control for potential confounding by trauma exposure, the study included a trauma-exposed sample of police officers without PTSD, limiting generalizability.

    “At last, to control for the potential confounding effect of trauma exposure, we included a trauma-exposed sample of police officers without PTSD, limiting the generalizability of our findings.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Perception of attachment security was improved after OT administration in healthy male students.

    “Notably, perception of attachment security was improved after OT administration in healthy male students (Buchheim et al, 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Buchheim et al, 2009 source

      Not checked in the free run.

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

    Study design and conductreasoning

    The study did not standardize the phase of menstrual cycle of female participants.

    “Also, we did not standardize the phase of menstrual cycle our female participants were scanned in, to minimize time and hence potential differences in symptom severity between the two scanning sessions.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The study was registered in the Netherlands Trial Registry (NTR3516).

    “Registered in the Netherlands Trial Registry (number: NTR3516)”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Anxiously attached healthy males remembered their mother as less caring after OT administration, compared with placebo.

    “However, opposite effects of OT administration on attachment have also been found: anxiously attached healthy males remembered their mother as less caring after OT administration, compared with placebo (Bartz et al, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bartz et al, 2010 source

      Not checked in the free run.

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

    Premisecitation

    OT administration in anxiously attached BPD patients and healthy controls decreased cooperation and trust.

    “In addition, OT administration in anxiously attached BPD patients and healthy controls decreased cooperation and trust (Bartz et al, 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bartz et al, 2011 source

      Not checked in the free run.

37 of 37

  • The paper relies on this without support.

    Dampened amygdala reactivity to emotional faces is beneficial in PTSD patients.

    “Taken together, our results indicate presumably beneficial neurobiological effects of OT administration in male and female PTSD patients.”

  • The paper relies on this without support.

    Trauma-exposed police officers without PTSD are an appropriate control group to account for trauma exposure and isolate PTSD-related effects.

    “We included a highly traumaexposed control group to account for potential confounding effects of trauma exposure on neurobiology.”

  • The paper relies on this without support.

    This is the first study investigating neurobiological effects of OT administration in PTSD patients.

    “To our knowledge, this is the first study investigating neurobiological effects of OT administration in PTSD patients, as a first step to show the potential clinical importance of OT administration in PTSD patients.”

  • The authors state this as an assumption.

    Trauma-exposed controls had little to gain regarding fear regulation.

    “Presumably, our trauma-exposed controls did have little to gain regarding fear regulation”

  • The authors state this as an assumption.

    PTSD patients may benefit from improved fear regulation.

    “whereas PTSD patients may benefit from improved fear regulation.”
5 of 5

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?

  • Recent neuroimaging studies have reported oxytocin-induced increases in neural activation in regions, including the amygdala, which are associated with processing of salience and arousal.

    “These studies have reported oxytocin-induced increases in neural activation in regions, including the amygdala, which are associated with processing of salience and arousal (Frijling et al., 2016;Gorka et al., 2015;Koch 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 Koch et al., 2016

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: t(39) = -2.18,p = .037

    Minor

    The paper reports p = .037 here; recomputing from the test statistic and its degrees of freedom gives p = .035 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .037 · recomputed p = .035

1 of 1

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.

  • Doesn’t add upt(39) = -2.18reported p = .037 · recomputed p = .035

    “t(39) = -2.18,p = .037”

  • Consistentt(34) = 2.114reported p = .042 · recomputed p = .042

    “t(34) = 2.114, p = .042”

  • ConsistentF(1, 39) = 0.656reported p = .423 · recomputed p = .423

    “F(1,39) = 0.656, p = .423”

  • ConsistentF(1, 34) = 0.998reported p = .325 · recomputed p = .325

    “F(1,34) = 0.998, p = .325”

  • ConsistentF(1, 34) = 0.261reported p = .613 · recomputed p = .613

    “F(1,34) = 0.261, p = .613”

5 of 5

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • PTSD subgroup counts exceed the table total

    Minor

    Table 1 labels the PTSD group as 36 patients, but its male and female counts sum to 37.

    Reported 36 · recomputed 37

  • Female control education percentage is incorrect

    Minor

    The table reports 17 of 20 female controls in the middle education category as 90%; that fraction is 85%. The remaining 3 of 20 are likewise 15%, not the reported 10%.

    Reported 90 · recomputed 85

  • Emotion-block count is stated two ways

    Minor

    The methods say there were four blocks of each of two emotion conditions, but then specify two blocks of each condition-four emotion blocks in total.

  • Male control education percentage is incorrect

    Minor

    The table reports 16 of 20 male controls in the middle education category as 85%; that fraction is 80%. The remaining 4 of 20 are likewise 20%, not the reported 15%.

    Reported 85 · recomputed 80

  • Valence-dependent reactivity was not absent in both amygdalae

    Minor

    The abstract states without qualification that valence-dependent amygdala reactivity was absent in PTSD patients. The results instead report significantly greater right-amygdala activity for fearful-angry than happy-neutral faces in those patients; only the left-amygdala difference was absent.

5 of 5

Cites

Flagged first, then by citations

1 of the 66 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Carlier I, Gersons B (1992). Development of a scale for traumatic incidents in police work. Psychiatr Fenn 23: 59–70.
  2. First MB, Spitzer RL, Gibbon M, Williams JB (2012) Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Clinician Version, Administration Booklet. American Psychiatric Publishing Inc.: Arlington, VA.
  3. van Groenestijn M, Akkerhuis G, Kupka R, Schneider N, Nolen W (1999) Gestructureerd Klinisch Interview voor de vaststelling van DSM-IV As 1 Stoornissen [Dutch translation of the SCID-I/P]. Zwets & Zeitlinger: Lisse, the Netherlands.

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Related

Authors
Koch, S. B., van Zuiden, M., Nawijn, L., Frijling, J. L., Veltman, D. J., & Olff, M.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Corresponding author
Koch, Saskia BJ
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2015-09-25
Volume
41
Issue
6
Pages
1495-1504
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2015.299
PMC
PMC4832009
OpenAlex
W2315243510
Cited by
98
References
66
Citations by year
2026: 6 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 6 · 2019: 9 · 2018: 12 · 2017: 14 · 2016: 10 · 2015: 1
FWCI
15.31
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
oxytocin, post-traumatic stress disorder, amygdala reactivity, emotional facial expressions, sex differences, police officers, augmentation therapy, anxiety, trauma exposure, neuroimaging
MeSH terms
Administration, Intranasal, Adult, Amygdala, Brain, Double-Blind Method, Emotions, Facial Expression, Female, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Stress Disorders, Post-Traumatic, Anti-Anxiety Agents, Cross-Over Studies, Functional Neuroimaging

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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