Longitudinal smallRNAome changes in the transdiagnostic PsyCourse Study

• Applicants: Professor Dr. André Fischer; Privatdozent Dr. Urs Heilbronner
• Subject Area: Biological Psychiatry ; Human Cognitive and Systems Neuroscience ; Cognitive, Systems and Behavioural Neurobiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514201724

The PsyCourse Study is a longitudinal transdiagnostic study of severe mental discorders from the affective-to-psychotic spectrum, comprising 1320 patients and 466 healthy controls. Participants were deeply phenotyped at each of the four equally spaced study visits, spanning a total time period of up to 18 months. Additionally, a wealth of biomaterial was collected at each measurement point, that has only partly been analyzed. PsyCourse data are available via research proposals to the scientific community, and the authors are commitment to Open Science principles, making PsyCourse data as FAIR (Findable, Accessible, Interoperable, and Reusable) as possible for a genomic study of mental disorders. For almost all participants (more than 98%), SNP data (Illumina Global Screening Array) are available, and the smallRNAomes of more than 1,500 individuals at baseline have been sequenced. A small part of these data have already been analyzed and published with respect to cognition. Specifically, we have recently identified genetic variants that appear to be responsible for an inability to profit from repeated presentation of a test, measuring an aspect of Executive Functions (EFs, the Trail-Making-Test, part B). EFs, tightly associated with the prefrontal cortex, are important metacognitive abilities, that control and coordinate mental processes. They are distinct from but related to general intelligence. Importantly, EFs are impaired in severe mental disorders, and are a major determinant of social and vocational functioning, especially in severe mental disorders. Here, we plan to continue the sequencing of the smallRNAome of PsyCourse participants, extending our investigation to the longitudinal course. Specifically, it is of interest whether there are smallRNAome changes that covary with changes in executive performance. Furthermore, recent collaborative advances in machine learning have lead to an Open Source statistical toolbox for longitudinal clustering of PsyCourse data, identifying groups of individuals with similar courses over time. Data resulting from our planned endeavor will result in a large dataset with which a number of pressing research questions can be addressed, and which will eventually become available to the scientific community via the PsyCourse Open Science Principles. Additionally to the planned in-silico analyses, a crucial part of the grant proposal will be the mechanistic investigation of disease processes in animals and other model systems, such as induced pluripotent stem cells (IPSCs). The proposed project will follow Open Science principles as closely as possible, and will thus make a long-lasting contribution to neuroscience.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Peter Falkai; Professor Dr. Thomas G. Schulze