Dimensional reconstruction of psychotic disorders through multimodal genetic-neural profiles

• Applicant: Emanuel Schwarz, Ph.D.
• Subject Area: Biological Psychiatry ; Epidemiology and Medical Biometry/Statistics
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255466206

Psychotic disorders are among the most serious mental illnesses and major causes of disability, absence from work and early retirement. A major problem is that current diagnostic criteria are based on symptom and clinical course criteria, which, almost by definition, do not map to the underlying biology. As a consequence, genetic illness associations regularly cross diagnostic boundaries and are hallmarked by small effect sizes due to the polygenic disease architecture and heterogeneity of diagnostic constructs. Here, we propose the investigation of trans-diagnostic patient subgroups based on underlying biological processes for dimensional reconstruction of psychotic disorders. For this purpose, we will link genetic variation to higher-order biological information as well as brain structure and function in an extensive multi-modal database amenable for quantitative analysis. We will utilize cutting-edge tools to perform patient subgroup identification in this database and identify polygenic profiles mapped onto gene functional categories that drive subgroup formation. We will then explore the relationship between patient subgroups and differences in brain structure, function and connectivity to elucidate the neuromodulatory role of the identified genetic-risk profiles.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Dezentrale Rechenanlage
• Instrumentation Group: 7030 Dedizierte, dezentrale Rechenanlagen, Prozeßrechner