Disentangling Effects of Oxytocin on Cognitive and Reactive Fear and the Moderating Role of the Receptor for Advanced Glycation End-products
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Neural substrates of emotion processing, measured via blood-oxygen-level dependent (BOLD) signal in the amygdala and striatum
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA)
- •healthy male volunteers
- •right handed
排除标准
- •current psychiatric illness
- •current psychiatric medication or psychotherapy
- •MRI contraindication (e.g. metal in body, claustrophobia)
研究组 & 干预措施
RAGE polymorphism (TT)
30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TT) will be selected and scanned twice.
干预措施: Oxytocin nasal spray (Drug)
RAGE polymorphism (TT)
30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TT) will be selected and scanned twice.
干预措施: Placebo (Drug)
RAGE polymorphism (TA/AA)
30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TA/AA) will be selected and scanned twice.
干预措施: Oxytocin nasal spray (Drug)
RAGE polymorphism (TA/AA)
30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TA/AA) will be selected and scanned twice.
干预措施: Placebo (Drug)
结局指标
主要结局
Neural substrates of emotion processing, measured via blood-oxygen-level dependent (BOLD) signal in the amygdala and striatum
时间窗: 30 minutes after nasal spray administration
Functional magnetic resonance imaging will be performed to measure the BOLD signal in response to emotional face stimuli. The investigators specifically plan to investigate neural responses to emotional faces in amygdala and striatal subregions. The BOLD signal in response to fearful faces relative to neutral faces and happy faces relative to neutral will be compared between the oxytocin and placebo sessions. To examine effects of the Receptor for Advanced Glycation End Products (RAGE), analyses of variance (ANOVAs) with the between subjects factor RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA) will be conducted on the second level. For analyses of fMRI data, default procedures of the software SPM12 will be adapted for ultra-high-field imaging. The family-wise error rate will be used to correct p-values for multiple comparisons and p \< .05 will be considered significant.
Flight distance and difficulty ratings in the flight initiation distance (FID) task
时间窗: 45 minutes after nasal spray administration
Behavioral data of the FID task (flight distance and difficulty ratings ) will be analyzed using mixed ANOVAs in the software SPSS with treatment (oxytocin vs. placebo) as within-subject factor and RAGE polymorphism (TT vs. TA/AA) as between-subject factor. Post-hoc t-tests will be Bonferroni-corrected. Behavioral data will be correlated with fMRI data of the FID task.
Neural responses in the flight initiation distance (FID) task
时间窗: 45 minutes after nasal spray administration
Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent (BOLD) signal in a flight initiation distance (FID) task, involving fast-, medium- and slow-attacking virtual predators that elicit distinct activations in the reactive and cognitive fear circuits. BOLD signals to different predator velocities will be analyzed. Analyses will focus on regions-of-interest associated with the processing of cognitive fear (vmPFC, PCC, hippocampus, and basolateral amygdala) and reactive fear (midbrain PAG, central amygdala, hypothalamus, and the MCC) and the reward system (striatum). To examine effects of the Receptor for Advanced Glycation End Products (RAGE), ANOVAs with the between-subject factor RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA) will be conducted on the 2nd level. For the fMRI data, default procedures of the software SPM12 will be adapted for ultra-high-field imaging.
次要结局
- Oxytocin concentration in blood plasma(10 minutes before nasal spray administration and 75 minutes after nasal spray administration)
- Concentration of receptor for advanced glycation endproducts (extracellular domain) in blood plasma(10 minutes before nasal spray administration)
研究者
Rene Hurlemann
Professor for Psychiatry
University of Oldenburg