Effects of Oxytocin on Cognitive and Reactive Fear (RAGE)

University Hospital Bonn (UKB)

Status and phase: Unknown; Phase 1

Conditions: Oxytocin

Treatments: Drug: Oxytocin nasal spray; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04292444

RAGE

Details and patient eligibility

About

The study examines the (sub)regional specificity of anxiolytic oxytocin (OXT) effects on emotional face processing and reactive and cognitive fear. Preliminary data indicate that the Receptor for Advanced Glycation End Products (RAGE) may regulate oxytocin transport into the brain. Thus, the study aims to replicate previous observations of oxytocin effects on the processing of fearful faces in the centro-medial amygdala and to assess whether a RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA), that has been shown to alter transcriptional activity, modulates anxiolytic OXT effects.

Full description

So far, no study examined selective oxytocin (OXT) effects on reactive (midbrain periaqueductal gray (PAG), central amygdala (CeA), hypothalamus, and the midcingulate cortex (MCC)) and cognitive fear (ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), hippocampus, and basolateral amygdala) and the reward system (striatum) with high spatial resolution. Previous studies showed that 7T functional magnetic resonance imaging (fMRI) results in a higher spatial resolution and specificity than 3T MRI in these brain regions and would thus allow for a more detailed characterization of the neural effects.

To disentangle (sub)region-specific effects of OXT on task-related activations of the cingulate structures, the amygdala, the striatum, PAG and VMPFC, the investigators plan to acquire ultra-high field 7T fMRI data from healthy male participants while they perform (i) an emotional face matching task and (ii) a flight initiation distance (FID) task involving fast- or slow-attacking virtual predators that elicit distinct activations in the reactive and cognitive fear circuits. Furthermore, participants will be pre-stratified depending on RAGE polymorphisms to elucidate possible RAGE-related differential OXT effects.

Enrollment: 60 estimated patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA)
• healthy male volunteers
• right handed

Exclusion criteria

• current psychiatric illness
• current psychiatric medication or psychotherapy
• MRI contraindication (e.g. metal in body, claustrophobia)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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60 participants in 2 patient groups

RAGE polymorphism (TT)

Experimental group

Description:

30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TT) will be selected and scanned twice.

Treatment:

Drug: Oxytocin nasal spray

Drug: Placebo

RAGE polymorphism (TA/AA)

Experimental group

Description:

30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TA/AA) will be selected and scanned twice.

Treatment:

Drug: Oxytocin nasal spray

Drug: Placebo