Neurobiology of the Major Psychoses – Transdiagnostic and longitudinal characterisation of schizophrenia and affective disorders

主要精神病的神经生物学 – 精神分裂症和情感障碍的跨诊断和纵向表征

• 批准号: 437618198
• 负责人: Professor Dr. Udo Dannlowski
• 金额: --
• 依托单位: Klinik für Psychische Gesundheit
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/437618198?language=en
• 关键词: Neurobiology; Major; Psychoses; Transdiagnostic; longitudinal

Progress in etiological research not only in schizophrenia, but all major psychoses (major depression, MDD; bipolar disorder, BD; schizophrenia, SZ and schizoaffective disorder, SZA), is hampered by obvious shortcomings in the majority of studies, mainly due to practical implementation. These limitations are most evident in MR brain imaging studies nested with biological (e.g. genetics, immunology, microbiome) and/or environmental or behavioural factors (e.g. environmental risks, clinical variables). Most studies are limited to small sample sizes and show massive heterogeneities across investigations, and almost no direct replications with identical methods. Furthermore, longitudinal MR imaging studies in schizophrenia are scarce, and are lacking for transdiagnostic approaches. Thus, there is a need for a novel generation of studies employing a) large-scale samples, b) longitudinal designs, c) multimodal (structural and functional) imaging approaches in d) well-defined, deeply phenotyped patients and control samples which are e) analysed with latest genetic and epigenetic methods and f) innovative multi-omics molecular approaches. To truly advance the field beyond the state of the art, g) a transdiagnostic approach with several patient groups based on h) multivariate analyses of multimodal (imaging) data from these patient groups and i) independent replications will be a necessary next step.The objective of the current proposal is to investigate 300 patients with SZ and SZA at two time points, 2 years apart, applying a deep phenotyping approach with multimodal MRI, GWAS, cytokines, microbiome analyses, environmental and, among others, life time risks, neuropsychology, personality and multiple clinical/sociodemographic variables. The identical protocol of the DFG FOR2107 will be applied, by which a total n=2577 patients (MDD, BD, as well as n=180 patients with SA/SZA, the latter phenotyped at own costs) and healthy control subjects have already been included (as of 5/2019). The present grant would cover the costs for recruitment and analysis of the remaining 120 patients with SZ/SZA at baseline and 144 after 2 years follow up, data analysis, and publications (see preamble). It would significantly augment the existing FOR2107 data set in multiple ways with high cost-effectiveness. The project will provide a large and unique cohort of SZ and SZA patients, with novel opportunities to study GxE interactions on multiple (epi-)genetic and (endo-) phenotypic levels across time. It will delineate new pathophysiological entities with common neurobiological underpinnings and will pave the way for an etiologic understanding of SZ and, in combination with the DFG FOR2107 data, of the major psychoses, potentially leading to their prevention, the prediction of individual disease courses, and novel therapies in the future.

病因学研究的进展不仅在精神分裂症，但所有重大精神病（重性抑郁症，MDD;双相情感障碍，BD;精神分裂症，SZ和情感障碍，SZA），是阻碍了明显的缺点，在大多数研究，主要是由于实际执行。这些局限性在与生物学（例如遗传学、免疫学、微生物组）和/或环境或行为因素（例如环境风险、临床变量）嵌套的MR脑成像研究中最为明显。大多数研究仅限于小样本量，并且在调查中显示出巨大的异质性，并且几乎没有使用相同方法的直接重复。此外，纵向磁共振成像研究精神分裂症是稀缺的，缺乏跨诊断的方法。因此，需要新一代的研究，其采用a）大规模样品，B）纵向设计，c）多模式（结构和功能）成像方法，d）明确定义的、深度表型化的患者和对照样品，其e）用最新的遗传和表观遗传方法分析，和f）创新的多组学分子方法。为了真正推动该领域超越现有技术水平，g）基于h）来自这些患者组的多模态（成像）数据的多变量分析和i）独立重复的几个患者组的转诊断方法将是必要的下一步。当前提议的目的是在两个时间点调查300名SZ和SZA患者，间隔2年，应用多模态MRI、GWAS、细胞因子、微生物组分析、环境和终身风险、神经心理学、人格和多个临床/社会人口学变量的深度表型分析方法。将应用与DFG FOR 2107相同的方案，共纳入了n=2577例患者（MDD、BD以及n=180例SA/SZA患者，后者的表型分析费用自理）和健康对照受试者（截至2019年5月）。现时的拨款会支付招募和分析其馀120名在基线时患有SZ/SZA的病人，以及144名在2年后跟进的病人、数据分析和出版物的费用（见序言）。它将以多种方式以高成本效益显著增强现有的FOR 2107数据集。该项目将为SZ和SZA患者提供一个庞大而独特的队列，为研究GxE随着时间的推移在多种（表观）遗传和（内）表型水平上的相互作用提供新的机会。它将描绘新的病理生理学实体与共同的神经生物学基础，并将铺平道路的病因学理解SZ，并结合DFG FOR 2107的数据，主要精神病，可能导致他们的预防，预测个别疾病的进程，并在未来的新疗法。