Neurobiology of affective disorders: 5 year longitudinal deep phenotyping of the Marburg/Münster Cohort Study (MACS)

• Applicants: Professor Dr. Bernhard Theodor Baune; Professor Dr. Udo Dannlowski; Professor Dr. Tilo Kircher; Professor Dr. Igor Nenadic
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Biological Psychiatry
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437615541

The long-term course of illness in major depressive disorder (MDD) and bipolar disorder (BD) is an important phenotypic feature that guides diagnosing, treatment and prognostic considerations in clinical practice. It is the course of affective disorders (AD, i.e. MDD and BD) over years that determines suffering and economic burden. In stark contrast to these insights, etiological research has widely focussed on cross-sectional designs. Main reasons are the lack of funding, long-term personal devotion and infrastructure for large-scale, longitudinal studies assessing multiple data domains such as clinical data, imaging, and blood-based biomarkers on a high quality level over periods well beyond a year. To address this lack of neurobiological research on the course of AD was the main motivation for the DFG-FOR2107, establishing a framework driven by taking the course of illness into the perspective of biological research questions. Within FOR2107, the Marburg-Münster Affective Disorder Cohort (MACS), has been established – a huge sample of currently N=2577 patients, controls, and healthy at-risk participants included for baseline assessment (T1), and followed-up after 2 years (T2, ongoing). MACS included a multi-omics approach for all participants at both observations (T1 and T2), assessing brain structure and function in the course of 2 years. Furthermore, a broad set of biomaterial matrices was acquired within a certified biobank. The core feature of MACS is the deep clinical phenotyping, an extensive battery of validated interviews, neuropsychological testing, and questionnaires. FOR2107 thereby met the pressing needs for a new generation of studies employing a) large-scale samples, b) longitudinal designs, c) multimodal imaging approaches in d) well-defined, deeply phenotyped patients, controls, and at-risk samples, which are e) analysed with latest genetic and epigenetic methods and f) innovative multi-omics approaches, using g) transdiagnostic samples, and h) latest high-dimensional, multivariate bioinformatics techniques, which are i) replicated independently. With our highly effective FOR2107 infrastructure we are able to address all these points. However, although MACS provides invaluable data for a 2-year period in affective disorders, this mid-term period is still not desirable for addressing important questions regarding the long-term course, e.g. subsamples of converters (from HC or at-risk participants to disease onset; diagnostic shifts from MDD to BD or other disorders); occurrence of co-morbidities; prospective influence of life-events on disease trajectories or long-term functional outcomes. Therefore, an extension of the observation period to a 5-year follow-up would meet this necessity and is the main goal of the present application. Due to the implemented FOR2107 infrastructure, an extension of this observation period is a highly cost-effective measure, furthermore heavily co-funded by the participating institutions

• DFG Programme: Research Grants