Dissecting the neurobiology of anxiety across diagnostic categories – the extension of the Marburg/Münster affective disorders cohort study (MACS) regarding anxiety disorders

• Applicants: Professor Dr. Udo Dannlowski; Professor Dr. Tilo Kircher; Professor Benjamin Straube, Ph.D.
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Biological Psychiatry
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437618337

Advances in etiology research in anxiety disorders (AXD) are often hampered by small sample sizes, high heterogeneity between studies, and lack of replication in independent samples. Furthermore, there are only few longitudinal MRI studies and transdiagnostic approaches are completely missing. However, transdiagnostic approaches are particularly important for AXD, considering the high comorbidity of about 40-70 % between AXD and affect disorders (AD, ie, major depressive disorder (MDD) and bipolar disorder (BD)), which can be explained at least in part by a high intersection of genetic and environmental risk factors. Thus, there is an emerging need for a novel generation of studies employing a) large-scale samples, b) longitudinal designs, c) structural and functional imaging approaches in d) well-defined, deeply phenotyped patients and control samples carrying genetic, environmental, and both risk factors, which are e) analysed with latest genetic and epigenetic methods and f) innovative multi-omics molecular approaches. To truly advance the field, g) a transdiagnostic approach with several patient groups based on h) multivariate analyses of multimodal data from these patient groups and i) replication in other samples will be a necessary next step.The aim of the proposed project is the investigation of a total of 300 patients with AXD (panic disorder, agoraphobia, social phobia, multiple phobias, generalized anxiety disorder) at two time points, two years apart. Data collection, quality control and analysis procedures correspond to those of the DFG FOR2107 "Neurobiology Affective Disorders" (www.FOR2107.de). Phenotyping includes multimodal MRI imaging, GWAS, cytokines, microbiome, environmental and lifetime risks, neuropsychology, personality traits and clinical parameters. As of May 2019, 2577 subjects (healthy, MDD, BD) were examined in the FOR2107 for the first and 1262 for the second measurement time. Of the patients with AD, 42% have a comorbid AXD. The present application comprises the recruitment and analysis of 300 patients with AXD at the first and 225 patients at the second measurement point after two years. This approach extends the existing, unique data of the FOR2107 in manifold ways at manageable costs. The data analyzes will include both univariate, hypothesis-driven approaches, but especially multi-dimensional analyzes with machine learning techniques for the multi-omics approaches.The proposed project will open up a large, unique cohort of patients with AXD, making it possible for the first time to analyze gene-environment interactions based on multiple (epi-) genetic and (endo) phenotypic data in a transdiagnostic and longitudinal design. This allows new pathophysiological entities to be defined on a neurobiological basis. These will fundamentally broaden the understanding of the etiology of AXD and contribute to the prevention, prediction of individual disease progression, and the development of new therapies.

• DFG Programme: Research Grants