Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals

Frijling, Jessie L.; Zuiden, Mirjam van; Koch, Saskia B.J.; Nawijn, Laura; Veltman, Dick J.; Olff, Miranda

doi:10.1038/npp.2015.278

Cited by 53 publications

(47 citation statements)

References 74 publications

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“…Effects of oxytocin in the VMPFC appear to be more indirect than those in the amygdala (Petrovic et al , 2008; Meyer-Lindenberg et al , 2011), consistent with this region’s role in the top-down regulation of amygdala function (Phelps et al , 2004) and its more general role as a hub for integrating affective signals that bear on decision-making (Bechara et al , 1994; Rangel and Hare, 2010; Padoa-Schioppa and Cai, 2011). Consistent with the above, a recent study found that oxytocin administration shortly after experiencing trauma decreased amygdala-VMPFC functional connectivity during trauma related imagery when compared to placebo (Frijling et al , 2015). …”

Section: Introductionsupporting

confidence: 61%

Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment

Bernhard

Chaponis

Siburian

et al. 2016

Soc Cogn Affect Neurosci

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Moral judgments are produced through the coordinated interaction of multiple neural systems, each of which relies on a characteristic set of neurotransmitters. Genes that produce or regulate these neurotransmitters may have distinctive influences on moral judgment. Two studies examined potential genetic influences on moral judgment using dilemmas that reliably elicit competing automatic and controlled responses, generated by dissociable neural systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate genes and identified a nominal association between a polymorphism (rs237889) of the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian moral judgment (that is, judgments favoring individual rights vs the greater good). An association was likewise observed for rs1042615 of the arginine vasopressin receptor gene (AVPR1A). Study 2 (N = 322) aimed to replicate these findings using the aforementioned dilemmas as well as a new set of structurally similar medical dilemmas. Study 2 failed to replicate the association with AVPR1A, but replicated the OXTR finding using both the original and new dilemmas. Together, these findings suggest that moral judgment is influenced by variation in the oxytocin receptor gene and, more generally, that single genetic polymorphisms can have a detectable effect on complex decision processes.

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Section: Introductionsupporting

confidence: 61%

Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment

Bernhard

Chaponis

Siburian

et al. 2016

Soc Cogn Affect Neurosci

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“…However, in our amygdala-centred functional connectivity paradigm (chapter 5; Frijling et al, 2016b), we concluded that the observed effects of oxytocin administration did not fit the salience processing theory, as oxytocin increased amygdala-posterior insula functional connectivity, whereas anterior insula function is generally implicated in salience processing (Menon & Uddin, 2010; Seeley et al, 2007). Of note, we did not investigate whether oxytocin administration affected (anterior) insula functional reactivity, which would have provided important additional information with respect to oxytocin administration effects on salience processing.…”

Section: Discussionmentioning

confidence: 75%

Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals

Frijling

2017

European Journal of Psychotraumatology

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Background: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which develops in approximately 10% of trauma-exposed individuals. Currently, there are few early preventive interventions available for PTSD. Intranasal oxytocin administration early posttrauma may prevent PTSD symptom development, as oxytocin administration was previously found to beneficially impact neurobiological (e.g. amygdala reactivity) and socio-emotional PTSD vulnerability factors. Objective: The overall aim of this dissertation was to investigate the potential of intranasal oxytocin administration as early preventive intervention for PTSD. Methods: We performed a functional magnetic resonance imaging (fMRI) study to assess the acute effects of a single administration of oxytocin on the functional fear neurocircuitry – consisting of the amygdala and (pre)frontal brain regions – in recently trauma-exposed emergency department patients (range n = 37–41). In addition, we performed a multicentre randomized double-blind placebo-controlled clinical trial (RCT) to assess the efficacy of repeated intranasal oxytocin administration early after trauma for preventing PTSD symptom development up to six months posttrauma (n = 107). Results: In our fMRI experiments we observed acutely increased amygdala reactivity to fearful faces and attenuated amygdala-ventromedial and ventrolateral prefrontal cortex functional connectivity after a single oxytocin administration in recently trauma-exposed individuals. However, in our RCT we found that repeated intranasal oxytocin administration early posttrauma reduced subsequent PTSD symptom development in recently trauma-exposed emergency department patients with high acute PTSD symptoms. Conclusions: These findings indicate that repeated intranasal oxytocin is a promising early preventive intervention for PTSD for individuals at increased risk for PTSD due to high acute symptom severity. Administration frequency dependent effects of oxytocin or the effects of oxytocin administration on salience processing may serve as explanatory frameworks for the contrasting oxytocin effects on anxiety-related measures in our clinical and neuroimaging studies.

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“…With respect to trauma, after the baseline visit of a randomized clinical trial testing the effects of 40 IU of twice-daily OT on the development of symptoms of PTSD among emergency department patients within two weeks of trauma, a single dose of IN OT was shown to increase amygdala reactivity to fearful faces, 119 and, in response to trauma reminders, reduced amygdala-ventromedial PFC connectivity and increased amygdala–insula functional connectivity. 120 This is potentially due to increased salience of fear stimuli during the sensitive post-trauma recovery period. 121,122 However, effects of single versus repeated administration appear to differ, with repeated IN OT administration potentially required to achieve clinically significant effects among high-risk individuals.…”

Section: Treatment Opportunitiesmentioning

confidence: 99%

Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities

Sippel

Allington²,

Pietrzak

et al. 2017

Chronic Stress

Self Cite

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Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social–emotional brain. In this review, we present an overview of evidence supporting OT’s utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e.g., the salience network and hypothalamic–pituitary–adrenal axis). Third, we present the sparse but promising findings from clinical populations, followed by discussion of critical moderating variables to consider in the service of maximizing the therapeutic potential of OT (e.g., patient sex and child maltreatment). We also identify heterogeneous findings and limitations of existing research, including reliance on single-dose studies in psychiatrically healthy samples and unanswered questions regarding the effectiveness of IN drug delivery and dosing schedules. Well-controlled multidose studies including women and measures of potentially moderating variables are sorely needed and would inform our understanding of the utility of OT for preventing and treating stress-related psychiatric disorders.

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Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals

Cited by 53 publications

References 74 publications

Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment

Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment

Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals

Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities

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