Targeting Autophagy in Depression: Fasting, Exercise, Diet
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
研究概览
简要总结
Depression is a common mental health condition that affects millions of people worldwide and is a leading cause of disability. Although current treatments can be effective, many patients do not fully recover or experience long-term improvement. This study aims to better understand how lifestyle factors such as physical activity and diet-related processes may influence biological mechanisms that could be linked to depression.
The study focuses on a natural cellular process called autophagy, which helps cells remove damaged components and maintain healthy function. Autophagy is influenced by energy availability in the body and may be affected by behaviors such as physical exercise and caloric restriction. Early evidence suggests that changes in autophagy may also be linked to mood regulation and depression, but this relationship is not yet well understood in humans.
In this exploratory study, we will investigate how physical activity influences autophagy and related metabolic and molecular processes in healthy adults. We will also examine whether these effects differ between individuals with different body weight and fitness levels, and between women and men.
A total of approximately 120 healthy adults aged 18 to 40 years will participate. Participants will be divided into four groups based on sex and body weight (normal weight or overweight). Each participant will attend study visits at the University Hospital Zurich and perform a standardized cycling exercise test under medical supervision.
During the exercise test, participants will perform a graded cycling protocol that gradually increases in intensity until exhaustion. We will collect small blood samples from a vein and from a fingertip at several time points before, during, and after exercise. Saliva samples will also be collected to measure stress-related hormones. Additional measurements include heart rate, breathing parameters, oxygen consumption, and physical performance.
Blood and saliva samples will be analyzed using advanced laboratory techniques to study changes in metabolism, immune signaling, hormones, gene activity, and markers related to autophagy. These analyses will help identify biological pathways that are activated by exercise and may be relevant to brain health and depression.
Participants will undergo medical screening before inclusion to ensure safety. Individuals with certain medical conditions or factors that could interfere with the study results will not be included. Participation is voluntary, and participants may withdraw at any time without consequences.
The study involves minimal risks associated with blood sampling and intense physical exercise, which will be performed under close medical supervision. The expected benefit is improved scientific understanding of how lifestyle-related biological processes may be linked to mental health, which could support the development of new preventive or therapeutic strategies for depression in the future.
详细描述
Background and Rationale Depressive disorders are among the leading causes of disability worldwide and represent a major public health burden. Despite the availability of pharmacological and psychotherapeutic treatments, a substantial proportion of patients do not achieve full remission or experience relapse. Current antidepressant strategies primarily target monoaminergic systems and are often insufficient in addressing the biological heterogeneity of depression.
Emerging evidence suggests that metabolic regulation and cellular stress response pathways may play an important role in the pathophysiology of depression. In particular, associations between metabolic disorders (such as obesity and insulin resistance) and depressive symptoms indicate shared biological mechanisms. This has led to increasing interest in lifestyle-based interventions, including physical activity, dietary modification, and caloric restriction, as potential modulators of both metabolic and neuropsychiatric outcomes.
A central candidate mechanism linking metabolism and brain function is autophagy, a conserved cellular process responsible for the degradation and recycling of damaged proteins and organelles. Autophagy is tightly regulated by nutrient availability and energy status, primarily via the AMPK-mTOR signaling axis. It is activated under energy deprivation and suppressed under nutrient excess. Proper autophagic flux is essential for neuronal homeostasis, immune regulation, and cellular stress adaptation.
Preclinical and emerging clinical evidence suggests that impaired autophagy may be involved in psychiatric disorders, including depression. Furthermore, interventions such as physical exercise, caloric restriction, and certain pharmacological agents have been shown to modulate autophagy-related pathways. However, the direct measurement of autophagic flux in humans under physiological conditions remains methodologically challenging, and its relationship to exercise-induced metabolic and neurobiological changes is not fully understood.
This study aims to address this gap by investigating autophagy-related biological responses to acute physical exercise in humans using a multi-omics approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age: 18-40 years
- •BMI: between 18.5 and 24.9 kg/m2 (SG1/2) or BMI between 25.0 and 39.9 kg/m2 (SG3/4)
- •ability to understand the study procedure and give consent
- •Written informed consent
- •SG1 women: any fitness level
- •SG2 men: VO2max < 45 ml/kg/KG29,30
- •Available to conduct CPET on menstrual cycle days 1-5 (SG1/3)
- •No infection with HIV or Hepatitis B/C
排除标准
- •No infectious illness for at least two weeks prior to the test
- •No vitamin supplementation during the week prior to the performance test
- •SG3 and SG4: More than 1 hour moderate exercise per week
- •No use of hormonal contraceptives in the last 6 months before the onset of the study (SG1/3)
- •a clinically diagnosed menstrual disorder (e.g., polycystic ovarian syndrome or amenorrhea) (SG1/3)
- •having given birth within the 12 months before inclusion in the study (SG1/3)
- •pregnancy or breastfeeding (SG1/3)
- •premenstrual dysphoric disorder (PMDD) (SG1/3)
- •history of epileptic seizure
- •history of depression
- •history of manic or psychotic episode
- •existing/current eating disorders (bulimia nervosa, anorexia nervosa) within the past 5 years
- •inability to communicate adequately in speech
- •inability to follow instructions
- •regular use of medication other than thyroxine
- •alcohol consumption as equivalent doses of more than 12 g of pure alcohol per day on average for women and 24 g of pure alcohol per day for men
- •vegan diet
- •daily nicotine consumption
- •currently or history of (regular) consumption of illegal drugs within the last year
- •known diseases of the cardiovascular system
- •arterial hypertension above 160/90 mmHg at rest
- •known pulmonary diseases
- •arthritis and rheumatic diseases and conditions
- •hematologic diseases
- •bronchial asthma
- •surgery less than 4-6 months ago
- •orthopedic or other diseases (e.g. neurological) that preclude maximum load on the bicycle ergometer
- •anemia (<12.0 g/dl for women and <14.0 g/dl for men)