Dissecting the neurobiology in the course of affective disorders - the Marburg/Münster affective disorders cohort study (MACS)

本项目(WP1)是FOR2107的人类骨干研究。在第一个资助期，成功地建立了一个大型队列--马尔堡/明斯特情感障碍队列研究(MACS)。样本2500人，包括1.1000名情感性精神障碍患者(预计700名MDD和300名BD)，包括精神分裂症和分裂情感性精神障碍患者；2.500名携带遗传(一级相对影响)、环境(儿童期虐待)或同时携带这两种危险因素的健康危险受试者；3.1000名无已知危险因素的健康受试者。所有参与者都通过多模式磁共振成像、临床评估、神经心理学和生物材料分析进行了深入的表型分析。成像电池包括三种功能范式，两种在情绪处理过程中探测神经生物学反应(特别是杏仁核功能)的神经生物学反应，以及一种引发强大海马区激活的情景记忆范式。用结构T1图像的形态计量学方法研究大脑结构，并利用DTI序列研究脑白质结构。WP1为分子WPS(WP3-5)中的人体部分获取并提供生物材料收集，这些材料将在中央生物库项目(CP1)内储存、处理和分发。WP5将对WP1受试者进行(EPI-)遗传和转录组分析，包括全基因组关联数据(GWAS)。在WP4中，将研究免疫机制，在WP3中，将进行有关miRNA调节的分析。第二个资助期的目标是对整个队列进行为期两年的跟踪，这项工作已经开始，采用了整个表型组合，包括成像和生物材料获取。该项目将建立一个独特的大型成像和生物材料数据库，用于验证关于基因、环境和基因-环境相互作用在疾病纵向过程中对大脑结构和功能的假说。特别是，第二个资助期的后续数据能够分析疾病病程的预测和新的、生物信息的亚群(生物型)的聚集。数据分析是与统计和方法工作包(WP6)密切合作进行的，以确保在数据收集过程中磁共振成像的可靠性和对生物类型数据简化程序的统计支持、关于脑成像数据的全球数据分析以及基于机器学习的新方法的实施。与这个FOR的嵌套WPS一起，WP1将有助于为情感障碍的病因学和纵向过程的神经生物学验证概念铺平道路。

The present project (WP1) serves as the human backbone study of FOR2107. During the 1st funding period, a large cohort was successfully established, the Marburg/Münster Affective Disorders Cohort Study (MACS). The sample (total N=2500) includes 1. n=1000 patients suffering from affective disorders (projected n=700 MDD and n=300 BD), extended by subsamples of schizophrenia and schizoaffective disorder patients, 2. n=500 healthy risk subjects either carrying genetic (1st degree relative affected), environmental (childhood maltreatment) or both risks factors, and 3. n=1000 healthy subjects without known risk factors. All participants were deeply phenotyped by multimodal MR-imaging, clinical assessment, neuropsychology, and biomaterial analyses. The imaging battery includes three functional paradigms, two probing neurobiological responses during emotion processing (particularly amygdala function), and an episodic memory paradigm eliciting robust hippocampus activation. Brain structure is investigated by morphometric methods on structural T1-images, and a DTI sequence was employed for investigating white matter structure. WP1 acquires and provides a biomaterial collection for the human parts in the molecular WPs (WP3-5), which will be stored, processed and distributed within a central biobanking project (CP1). (Epi-)Genetic- and transcriptome analyses on WP1 subjects, including genome-wide association data (GWAS) will be conducted in WP5. In WP4, immune mechanisms will be investigated and in WP3, analyses regarding miRNA regulation are conducted. Objective of the 2nd funding period is the 2-year follow-up of the entire cohort, which has already started, employing the entire phenotyping battery, including imaging and biomaterial acquisition. The project will build up a unique, large imaging and biomaterial database which will serve to validate hypotheses regarding gene, environment, and gene-environment interactions on brain structure and function in the longitudinal course of illness. Particularly the follow-up data of the 2nd funding period enables analyses regarding prediction of illness course and clustering of novel, biologically informed subgroups (biotypes). Data analyses are conducted in close collaboration with a statistical and methodological work package (WP6), assuring MRI reliability in the course of data collection and statistical support for biotype data reduction procedures, GWAS on brain imaging data, and the implementation of novel, machine learning based approaches. Together with the nested WPs of this FOR, WP1 will help to pave the way for a neurobiologically validated conception of the etiology and the longitudinal course of affective disorders.