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

Prof. Dr. Dr. Udo Dannlowski¹, Prof. Dr. Axel Krug², Prof. Dr. Igor Nenadić², Prof. Dr. Tilo Kircher²

¹University of Münster, Department of Psychiatry and Psychotherapy, Münster
²University of Marburg, Department of Psychiatry and Psychotherapy

The present project (Work Package 1) 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 Work Packages (Work Packages 3-5), which will be stored, processed and distributed within a central biobanking project (Central Project 1). (Epi-)Genetic- and transcriptome analyses on Work Package 1 subjects, including genome-wide association data (GWAS) will be conducted in Work Package 5. In Work Package 4, immune mechanisms will be investigated and in Work Package 3, 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 (Work Package 6), 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 Work Packages of this FOR, Work Package 1 will help to pave the way for a neurobiologically validated conception of the etiology and the longitudinal course of affective disorders.