A global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA Consortium

摘要 全世界每年有一百万人死于自杀。自杀是所有人的第十大死因 这是造成精神障碍青年人死亡的第二大原因。更多的人在 55岁以上的人死于自杀，而不是死于艾滋病毒、中风、流感、呼吸道疾病、慢性肺病和 凶案组每一个自杀未遂者中至少有20个自杀未遂者。更好的预防策略是 迫切需要;然而，机制，赋予自杀行为的风险增加（从自杀意念， 自杀未遂和自杀未遂）在很大程度上仍然未知。神经生物学改变与 自杀念头和行为史可以预测未来的风险，并为干预提供目标。调查 自杀行为的神经生物学研究受到低基础发生率和异质性的阻碍。 自杀企图的性质，需要来自世界各地的大量包容性样本，以了解潜在的 机制等我们建议在全球范围内开展合作，研究神经生物学和转诊断 精神障碍患者自杀行为的潜在机制迄今为止的研究已经 在自杀意念者和自杀者的小样本（通常N <50）中进行，并检查神经标记物 在单一精神疾病中的自杀行为我们将汇集现有的神经成像和临床数据， 大约23，000名患有和没有精神健康障碍的人组成了"谜-自杀" 思想和行为（STB）倡议。我们将整合和分析来自全球24个机构的数据集 （1）确定区分自杀和自杀的转诊断神经机制， 通过MRI，以及这些如何随年龄，性别和疾病特征而变化;（2） 整合不同的解释水平，并研究大脑机制之间的相互作用， 社会人口统计学、心理社会学、临床和认知风险因素对自杀行为的影响。我们将识别不同的 生物心理社会途径将自杀意念者与有自杀企图史的人区分开来， 根据不同的生物心理社会危险因素的结构产生新的自杀危险亚型;（3）去 超越对构思或尝试的二元分类，并对结构和 功能性脑回路潜在的细粒度维度表型的自杀行为的一个子集， 样品与自杀意念和自杀企图独特相关的跨诊断脑机制， 并与更深入的维度自杀行为表型，可以告知新的发展 直接或间接地针对这些脑回路的改变进行干预。生物心理社会自杀风险 通过这项研究确定的亚型可能突出了不同人群中自杀行为的不同途径。 因此，我们认为，在预防和干预战略的选择上，有可能做到个性化。

ABSTRACT One million people around the world die from suicide annually. Suicide is the tenth leading cause of death for all ages and the second leading cause of death among young people with mental disorders. More people under the age of 55 die by suicide than from HIV, stroke, influenza, respiratory diseases, chronic lung disease and homicide. There are at least 20 suicide attempts for every completed suicide. Better prevention strategies are urgently needed; yet, mechanisms that confer increased risk for suicidal behaviors (ranging from suicidal ideation to suicide attempts and completed suicide) remain largely unknown. Neurobiological alterations associated with a history of suicidal thoughts and behaviors may predict future risk and provide targets for interventions. Inquiry into the neurobiology of suicidal behaviors is hindered by a low base rate of occurrence and the heterogeneous nature of suicidal attempts, requiring large, inclusive samples from around the world to understand the underlying mechanisms. We propose a worldwide collaboration to study the neurobiological and transdiagnostic mechanisms underlying suicidal behaviors in people with mental disorders. Research to date has been performed in small (typically N<50) samples of suicidal ideators and attempters and examined neural markers of suicidal behaviors within a single mental illness. We will pool existing neuroimaging and clinical data from approximately 23,000 individuals with and without mental health disorders forming the “ENIGMA-Suicidal Thoughts and Behaviors (STB)” initiative. We will integrate and analyze datasets from 24 institutions worldwide in a cost-efficient manner to (1) identify transdiagnostic neural mechanisms that differentiate between suicidal ideators and suicide attempters through MRI, and how these vary with age, sex, and disease characteristics; (2) integrate differential explanatory levels and investigate interacting effects between brain mechanisms and sociodemographic, psychosocial, clinical and cognitive risk factors on suicidal behaviors. We will identify different biopsychosocial pathways that discriminate suicidal ideators from people with a history of suicide attempt, yielding novel suicide risk subtypes based on different configurations of biopsychosocial risk factors; (3) go beyond binary classifications of ideation or attempt and conduct an in-depth investigation of structural and functional brain circuitries underlying fine-grained dimensional phenotypes of suicidal behaviors in a subset of samples. Transdiagnostic brain mechanisms uniquely associated with suicidal ideation and suicide attempts, and with more in-depth dimensional suicidal behavior phenotypes, can inform the development of novel interventions directly or indirectly targeting alterations in these brain circuitries. The biopsychosocial suicide risk subtypes identified through this study may highlight distinct pathways to suicidal behaviors in different groups of people and have the potential for individualizing the selection of prevention and intervention strategies.