Circadian Disturbances in People With Mental Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Daytime Circadian variation in clock gene mRNA expression
研究概览
简要总结
Introduction
16.8% of the Danish adult population are obese (Body Mass Index> 30 kg / m2). Obesity increases the risk of lifestyle diseases such as type-2 diabetes and non-alcoholic fatty liver. People with mental illness have an increased risk of developing obesity. Both obesity and certain mental disorders (bipolar disorder and schizophrenia) are associated with circadian rhythm disorders. Clinically, this may manifest as reduced sleep quality, depressive symptoms and increased fatigue, but also deregulation of a wide range of bodily processes subject to the circadian rhythm.
In circadian rhythm disorders, the pattern of how mRNA of specific 'clock genes' is expressed in the cell may be affected. These clock genes are associated with obesity, bipolar disorder and schizophrenia. Despite the clear indications of an interplay between mental illness, obesity and circadian rhythm disorders, the relationship between these illnesses are largely unexplored.
Aim
The aim of this study is to investigate circadian disturbances in people with and without obesity, as well as people with obesity and a comorbid diagnosis of either schizophrenia or bipolar disorder.
Methods
The study population will consist of:
- People with obesity and schizophrenia (N=22)
- People with obesity and bipolar disorder (N=22)
- People with obesity without psychiatric disease (N=22)
- People with BMI 18.5 - 25kg/m2 and no psychiatric disease (N=20)
Study Procedure
Participants will visit the clinic 2 times. At each visit participants fill in questionnaires and perform physical tests. Between visit 1 and 2, participants will over a 2-day period (at-home), collect biological samples (Four hair- and six saliva samples per day). In addition, participants will wear accelerometers and continuous glucose monitors (CGMs) for a total of 8 days, including the 2-day sampling period.
Sampled hair follicles are analyzed for relative expression of clock gene mRNA. Saliva is analyzed for cortisol- and melatonin content. The four participants groups are analyzed and compared on daytime variation in mRNA expression, cortisol- and melatonin concentration, and body temperature.
Perspectives
A comparison of patient groups presenting with mental disease, obesity and circadian disturbances may provide new insight into the association between these diseases.
详细描述
Background
Obesity (30 ≥ kg/m2) is a major global health challenge. Worldwide obesity has nearly tripled since 1975 (WHO, 2021) and is projected to continue to rise throughout western society (OECD, 2017).
Obesity increases the risk of type-2 diabetes (T2D), obstructive sleep apnea (OSA), non-alcoholic fatty liver disease (NAFLD), hypertension, osteoarthritis, polycystic ovary syndrome and several other conditions (George et al., 2018; Luque-Ramirez et al., 2014; Mainous, Tanner, Jo, & Anton, 2016). Mortality is significantly increased, and a person with class III obesity (BMI > 40kg/m2) is predicted to live ten years shorter than a normal-weight person of same age (Finkelstein, Brown, Wrage, Allaire, & Hoerger, 2010). People with obesity have more days of sick leave, experience social disadvantages (Hernaes, Andersen, Norheim, & Vage, 2015) and report an overall poorer health-related quality of life compared to non-obese people (Kolotkin & Andersen, 2017).
Obesity and mental disease:
Mental disease is associated with increased risk of obesity. Obesity is approximately two and three times as prevalent in people with bipolar disorders and schizophrenia spectrum disorder compared to people without mental disease, respectively (Annamalai, Kosir, & Tek, 2017; Chao, Wadden, & Berkowitz, 2019; Sicras, Rejas, Navarro, Serrat, & Blanca, 2008). Many commonly used antipsychotic drugs induces weight gain with a magnitude ranging from neutral in some drugs to +5.3 kg in olanzapine (Vancampfort et al., 2015). Antipsychotic-induced weight changes depend of the underlying disease (Moteshafi, Zhornitsky, Brunelle, & Stip, 2012). Many mental diseases are associated with higher calorie intake, poorer food quality (Manu et al., 2015) and lower levels of physical activity (Schuch et al., 2017; Vancampfort et al., 2017).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fulfilling the criteria for one of the four study groups:
- •People with BMI > 30 kg/m2 and schizophrenia spectrum disorder (N=22)
- •People with BMI > 30 kg/m2 and bipolar disorder spectrum disorder (N=22)
- •People with BMI > 30 kg/m2 without psychiatric disease or sleep disorders (N=22)
- •People with BMI 18.5 - 25kg/m2 and no psychiatric disease or sleep disorders (N=20)
排除标准
- •Participants taking oral supplements of melatonin are excluded if pausing is deemed inappropriate.
结局指标
主要结局
Daytime Circadian variation in clock gene mRNA expression
时间窗: for two full consecutive days participant will pluck hairs and place the hair root in a dissolution buffer. Participants will each collect 4 samples per day: immediately after waking, and every 6th preceding hour, including immediately before bed.
Relative amount of different clock gene mRNA, compared to housekeeping gene
次要结局
- Daytime Circadian variation in saliva melatonin concentration(for two full consecutive days participant will collect saliva samples. Participants will each collect ~6 samples per day: immediately after waking, 6 and 12 hours after waking and every 2 hours until bedtime, including a sample immediately before bed.)
- Daytime Circadian variation in saliva cortisol concentration(for two full consecutive days participant will collect saliva samples. Participants will each collect ~6 samples per day: immediately after waking, 6 and 12 hours after waking and every 2 hours until bedtime, including a sample immediately before bed.)