Biomarkers to investigate Genetics, Environment and Mechanisms in Schizophrenia (Bio-GEMS).

Bio-GEMS：生物标记物，以揭示精神分裂症的遗传、环境和机制精神分裂症的病因是什么？精神病，包括精神分裂症和双相情感障碍，影响约3%的人口;他们在世界各地造成重大的社会和经济成本。有效的药物和心理治疗是可用的，然而，三分之一的患者对它们没有反应。此外，抗精神病药物有常见的副作用，这导致许多人停止服药和复发。副作用包括嗜睡、颤抖、性功能障碍和肥胖。精神障碍的产生既有环境因素，也有遗传因素。已确定的环境风险包括：影响婴儿大脑发育的妊娠和分娩并发症、大麻的使用（特别是在年幼时）、移民、在城市长大以及童年创伤。然而，精神病也在家庭中运行，遗传因素很重要，我们称之为“遗传变异”。有数百种遗传变异，在人群中很常见，但只会增加患精神病的风险。我们也知道一些非常罕见的遗传变异，但当存在时，患精神分裂症的风险增加了2到30倍。其中一些罕见的遗传变异也会增加学习障碍、自闭症、癫痫和其他健康问题的风险。有些人携带这些高风险的遗传变异，但他们保持健康，他们的恢复力的起源仍然是一个谜。尽管我们对精神病原因的理解取得了突破，但我们对遗传风险或恢复力如何产生的知识有限。我们打算使用最先进的脑功能生物标志物来研究认知和感知过程，这是精神障碍的关键。心理或脑电图测试和MRI扫描是安全的，并为实现这一目标进行了最佳设计。研究高风险遗传变异对大脑发育和功能的影响。2.了解为什么相同的高风险变体的一些携带者发展不同的神经或精神障碍，并确定弹性的遗传来源。3.调查携带高风险遗传变异的人是否更有可能继续经历不利的环境因素，这进一步增加了精神分裂症的风险。4.将我们的数据与大型国际研究中的其他项目进行联合收割机组合或比较。我们将如何进行研究？我们将分析已经参与我们研究的志愿者的大样本，包括精神分裂症，双相情感障碍或其他精神疾病患者和没有这些条件的对照组。超过14，000名参与者已经捐赠了DNA样本。他们中的许多人还完成了脑部扫描，脑电图（脑电图测试，如用于癫痫），认知和临床评估。我们将邀请另外3，000人参加该项目。所有样本都将用最新的基因组学技术进行检测。据我们所知，Bio-GEMS是精神病领域最大和最彻底的研究之一。为什么这很重要？Bio-GEMS将为遗传变异如何影响大脑解剖学，生理学和认知发展提供新的见解。了解精神病的遗传学对于开发新的药物和心理干预至关重要。遗传学的进步也将有助于识别患有精神病的高危人群，这些人将受益于早期获得治疗，从而更好地康复。

Bio-GEMS: BIOMARKERS TO INVESTIGATE GENETICS, ENVIRONMENT & MECHANISMS in SCHIZOPHRENIA WHAT ARE THE CAUSES OF PSYCHOSIS?Psychosis, including schizophrenia and bipolar disorder, affect about 3% of the population; they create major social and economic costs throughout the world. Effective medications and psychological therapies are available, however, one in three patients do not respond to them. Furthermore, antipsychotic drugs have common side effects, which contribute to many people stopping their medication and relapsing. Side effects can range from drowsiness to shaking, sexual dysfunction, and obesity.Psychotic disorders emerge from both environmental as well as genetic factors. Established environmental risks include: pregnancy and birth complications affecting a baby's brain development, the use of cannabis (especially if starting young), migration, growing up in a city, and childhood trauma. However, psychosis also runs in families and genetic factors are important, we refer to these as "genetic variants". There are hundreds of genetic variants, which are common in the population, but only convey small increases in risk for psychosis. We also know of a few genetic variants that are very rare, but when present, the risk of developing schizophrenia is increased between two and thirty-fold. Some of these rare genetic variants also increase the risk for learning disabilities, autism, epilepsy, and other health problems. Some people carry these high-risk genetic variants, yet they stay healthy, and the origin of their resilience remains a mystery. Despite breakthroughs in our understanding of the causes of psychosis, we have limited knowledge on how genetic risk or resilience come about. We intend to use state of the art biomarkers of brain function to investigate cognitive and perception processes that are key in psychotic disorders. Psychological or EEG tests and MRI scans are safe and optimally designed to achieve this.OBJECTIVES1. Investigate the influence of high-risk genetic variants on brain development and function. 2. Understand why some carriers of the same high-risk variant develop different neurological or mental disorders and identify genetic sources of resilience. 3. Investigate if people who carry high-risk genetic variants are more likely to go on to experience adverse environmental factors, which further increase schizophrenia risk. 4. Combine or compare our data with other projects in large international studies. HOW WILL WE DO THE RESEARCH?We will analyse a large sample of volunteers who already participated in our study including people with schizophrenia, bipolar or other psychotic disorders and controls without these conditions. More than 14,000 participants have already donated a DNA sample. Many of them have also completed brain scans, electroencephalograms (EEG tests like those used in epilepsy), cognitive and clinical assessments. We will invite another 3,000 individuals, to take part in the project. All samples will be tested with the latest genomics technology. To our knowledge, Bio-GEMS is one of the largest and most thorough studies in psychosis. WHY IS THIS IMPORTANT?Bio-GEMS will provide new insights into how genetic variants influence brain anatomy, physiology, and cognitive development. Understanding the genetics of psychosis, is essential to develop new medications and psychological interventions. Genetic advances will also help to identify people at high risk of developing psychosis, who will benefit from earlier access to treatments, leading to a better recovery.