Sex Differences in Heart-brain Crosstalk - Role of Psychosocial Stress
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Difference between the rest and stress amygdala-to-cerebellum perfusion ratios (kBq/kBq)
研究概览
简要总结
The main study objective is to prospectively determine the influence of sex-related risk factors and psychosocial variables on neuronal stress responses and myocardial perfusion in a population of 64 female and male individuals 50-75 years of age and free of cardiovascular disease.
详细描述
The main objective of the project is to prospectively determine the influence of sex on amygdalar metabolic activity and myocardial perfusion in a population of healthy postmenopausal women and aged men under acute psychosocial stress conditions.
The primary hypothesis of the study is that women experience disproportionate amygdalar metabolic activity and reduced myocardial perfusion in response to psychosocial stress compared to men.
This project is a monocentric prospective observational study involving hybrid positron emission tomography/magnetic resonance (PET/MR) imaging as well as the collection of biological samples in healthy individuals aged 50-75 years (postmenopausal women, and men). To inflict acute psychosocial stress, the investigators applied the Montreal Imaging Stress Test (MIST) when the participants were inside the PET/MR scanner and the Trier Social Stress Test (TSST) when the participants were outside the PET/MR scanner. Both the TSST and the MIST are standardized tests and are widely applied to provoke reliable biological stress responses in a laboratory setting. No follow-up study is planned. At inclusion, individuals have been interviewed and health data have been collected through questionnaires. In addition, biological samples, including blood, nail and saliva have been collected. Volunteers underwent myocardial blood flow (MBF) and cerebral perfusion imaging using ammonia (13NH3)-PET, as well as functional imaging using magnetic resonance imaging (MRI), both routinely used imaging techniques. 13NH3-PET/MR has been conducted at rest and under stress (MIST). Subsequently, the study participants underwent a TSST, followed by whole body metabolic imaging with fluor-18-deoxyglucose (18F-FDG)-PET/MRI, allowing to study brain and bone marrow metabolism, among other parameters. In parallel, the heart rate response (HRR) has been monitored throughout the study and catecholamines were collected at baseline and after stress to assess the autonomic influence on the heart. The total radiation exposure was below 5 mSv.
In detail, each participant was asked to complete questionnaires to assess their psychometric baseline characteristics at the study visit.
Two blood samples were collected from a peripheral intravenous catheter, at the beginning of the study and the end of the TSST. Blood glucose levels were measured using a finger prick. In addition, saliva samples of approximately 1 mL each were taken at different time points, notably before and after each of the mental stress tests. Nail samples were collected by clipping nails from the fingers and/or toes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 50 Years 至 75 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Women and men that are between 50-75 years of age
- •Post-menopausal status in women
- •Normal body weight (BMI<30kg/m2)
- •Non-smoker or not smoking since ≥ 5 years or occasional smokers.
排除标准
- •Written informed consent was not provided
- •History of arterial hypertension
- •History of diabetes
- •History of cardiovascular disease
- •History of neurological disorders
- •History of cancer (unless considered in remission since at least 5 years and not having necessitated a systemic chemotherapy and/or a brain radiotherapy)
- •Use of steroids interfering with biomarker levels
结局指标
主要结局
Difference between the rest and stress amygdala-to-cerebellum perfusion ratios (kBq/kBq)
时间窗: 11-10-2021 to 20-11-2023
Sex differences in the amygdala perfusion between rest and stress, assessed by 13N-NH3-PET and defined as the amygdala perfusion (AmygP, expressed as kiloBecquerel, kBq) corrected to the perfusion of the cerebellum (expressed as kBq), following the Montreal Imaging Stress Task. The higher the magnitude of the AmygP/(Cerebellum perfusion) modification at stress compared to rest, the higher the amygdala response to mental stress (no threshold for normality)
Myocardial flow reserve (MFR, no unit)
时间窗: 11-10-2021 to 20-11-2023
Sex differences in myocardial flow reserve (MFR) as determined by 13N-NH3-PET, during the Montreal Imaging Stress Task. MFR is defined as the ratio between MBF at stress and MBF at rest (no unit). The higher the MFR, the higher the myocardial perfusion modification during the stress task (no threshold).
Amygdala-to-cerebellum ratio of glycolytic metabolic activities (SUV/SUV)
时间窗: 11-10-2021 to 20-11-2023
Sex differences in the stress-related neural activity (SNA) assessed by 18F-FDG-PET and defined as the amygdala metabolic activity (AmygA, expressed as standard uptake value, SUV) corrected to the metabolic activity of the cerebellum (expressed as SUV), following the Trier Social Stress Test. The higher the AmygA/(cerebellum activity) ratio, the higher the SNA (no threshold for normality)
次要结局
- Difference between the rest and stress amygdala-to-vmPFC perfusion ratios (kBq/kBq)(11-10-2021 to 20-11-2023)
- Noradrenaline (mL/min)(11-10-2021 to 20-11-2023)
- Interleukin-2 (IL-2, pg/mL)(11-10-2021 to 20-11-2023)
- Interleukin-4 (IL-4, pg/mL)(11-10-2021 to 20-11-2023)
- Tumor necrosis factor (TNF, pg/mL)(11-10-2021 to 20-11-2023)
- Salivary cortisol (mol/L)(11-10-2021 to 20-11-2023)
- Adrenaline (mL/min)(11-10-2021 to 20-11-2023)
- Bone marrow metabolic activity (SUV)(11-10-2021 to 20-11-2023)
- Amygdala-to-vmPFC ratio of glycolytic metabolic activities (SUV/SUV)(11-10-2021 to 20-11-2023)
- Myocardial blood flow (MBF) at rest (mL/g/min)(11-10-2021 to 20-11-2023)
- Gender score questionnaire(11-10-2021 to 20-11-2023)
- Left ventricular ejection fraction (LVEF, %)(11-10-2021 to 20-11-2023)
- Heart-rate response (HRR, no unit)(11-10-2021 to 20-11-2023)
- Dopamine (mL/min)(11-10-2021 to 20-11-2023)
- Vascular Cell Adhesion Molecule (VCAM)(11-10-2021 to 20-11-2023)
- Myocardial blood flow (MBF) at stress (mL/g/min)(11-10-2021 to 20-11-2023)
- Spleen metabolic activity (SUV)(11-10-2021 to 20-11-2023)
- Aorta metabolic activity (SUV)(11-10-2021 to 20-11-2023)
- Interleukin-10 (IL-10, pg/mL)(11-10-2021 to 20-11-2023)
- C-reactive protein (CRP, mg/L)(11-10-2021 to 20-11-2023)
- Interleukin-6 (IL-6, pg/mL)(11-10-2021 to 20-11-2023)
- Interleukin-8 (IL-8, pg/mL)(11-10-2021 to 20-11-2023)
- Matrix metalloproteinase-9 (MMP9, pg/mL)(11-10-2021 to 20-11-2023)
- Monocyte Chemoattractant Protein-1 (MCP1, pg/mL)(11-10-2021 to 20-11-2023)
