Work Package 1
Dissecting the neurobiology in the course of affective disorders – the Marburg-Münster affective disorders cohort study (MACS)
Prof. Dr. Dr. Udo Dannlowki1, 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 (WP1) serves as the human “backbone study” of the FOR. It aims at establishing and characterizing a large cohort (N=2500) of 1. n=1000 patients suffering from major depressive disorder (MDD; n=700) or bipolar disorder (BD; n=300), 2. n=500 healthy subjects either at genetic risk (1st degree relative affected, n=200), environmental risk (n=200) or both risks (n=100), and 3. n=1000 healthy subjects without known risk factors. All participants will be deeply phenotyped by multimodal MR imaging, clinical assessment, neuropsychology, and biomaterial analyses. Risk factors for affective disorders will be assessed with a focus on maltreatment vs. beneficial environment and genetic risk variants in the CACNA1C and NCAN gene. The imaging battery will include three functional paradigms probing neurobiological responses to emotional faces (particularly amygdala function), a working memory paradigm, and an episodic memory paradigm eliciting robust hippocampus activation. Brain structure will be investigated by morphometric methods on structural T1-images, and a DTI sequence will be employed for investigating white matter structure. WP1 will acquire and provide a biomaterial collection for the human parts in the molecular WPs
(WP3-5), which will be stored in a central biobanking project (CP1). Genetic analyses on WP1 subjects, including genome-wide association data (GWAS) will be conducted in WP5 and additionally three major epigenetic processes will be investigated: microRNA profile in selected risk subjects (WP3), DNA methylation (WP5), and histone modification (CP1). The whole cohort will be completely re-assessed after 2 years (and post-funding after 4 years). The project will build up a unique large imaging and biomaterial database which will serve to validate hypotheses regarding gene (G), environment (E) and G x E interactions on brain structure and function in the longitudinal course of illness. Data analysis will be 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, and GWAS on brain imaging data. The Marburg Affective Disorders Cohort Study (MACS) will recruit mainly from a rural population with low mobility, making the set-up ideal for a longitudinal cohort study. 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.