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

本项目（WP1）作为FOR2107的人类骨干研究。在第一个资助期内，成功地建立了一个大型队列，即马尔堡/马尔堡/马尔堡综合征情感性障碍队列研究（MACS）。样本（总N=2500）包括1。n=1000名情感障碍患者（预计n=700名重度抑郁症患者和n=300名重度抑郁症患者），通过精神分裂症和分裂情感障碍患者的亚样本进行扩展，2。N =500名健康风险受试者，携带遗传（一级亲属受影响）、环境（儿童虐待）或两种风险因素；N =1000名无已知危险因素的健康受试者。通过多模态磁共振成像、临床评估、神经心理学和生物材料分析，对所有参与者进行了深入的表型分析。成像电池包括三个功能范式，两个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），以及一个情景记忆范式，引发强大的海马体激活。采用形态计量学方法对结构t1图像进行脑结构研究，采用DTI序列对脑白质结构进行研究。WP1获取并提供分子WPs （WP3-5）中人体部位的生物材料收集，这些生物材料将在中央生物银行项目（CP1）中存储、处理和分发。（Epi-） WP1受试者的遗传和转录组分析，包括全基因组关联数据（GWAS）将在WP5中进行。在WP4中，将研究免疫机制，在WP3中，将分析miRNA调控。第二个资助期的目标是对整个队列进行为期2年的随访，该随访已经开始，采用整个表型电池，包括成像和生物材料获取。该项目将建立一个独特的、大型的成像和生物材料数据库，用于验证有关基因、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设。特别是第二个资助期的随访数据，可以对疾病病程的预测和新的、生物学上知情的亚群（生物型）的聚类进行分析。数据分析是与统计和方法学工作包（WP6）密切合作进行的，确保MRI在数据收集过程中的可靠性，并为生物型数据简化程序、脑成像数据的GWAS以及基于机器学习的新方法的实施提供统计支持。与此FOR的嵌套WPs一起，WP1将有助于为情感性障碍的病因学和纵向病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.