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Sketchpad Series

Neuroimmunological Mechanisms of Psychosis - a Network Perspective with The Virtual Brain

Poster Session E - Monday, March 31, 2025, 2:30 – 4:30 pm EDT, Back Bay Ballroom/Republic Ballroom
Also presenting in Data Blitz Session 4 - Saturday, March 29, 2025, 10:30 am – 12:00 pm EDT, Constitution B.

Christoph V. M. Huettl^1,2 (christoph.huettl@charite.de), Konstantin Bülau^1,2, Leon Martin^1,2, Luise Da Costa Zemsch^1,2, Rico A. Schmitt^1,2, Michael Schirner^1,2, Leon Stefanovski^1,2, Petra Ritter^1,2,3; ¹Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, ²Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department for Neurology and Experimental Neurology, Brain Simulation Section, Charitéplatz 1, 10117 Berlin, Germany, ³Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany

Psychosis is a severe psychiatric syndrome, with long-term quality of life most impaired by negative symptoms such as avolition and anhedonia, and cognitive deficits affecting memory and reasoning. Beyond genetic factors and substance abuse (e.g. cannabis and other hallucinogens), increasing evidence points to inflammatory imbalances —marked by elevated pro-inflammatory cytokines and imaging-based inflammatory biomarkers —as key factors for the development of psychosis. Functional connectivity (FC) changes have been found to be predictive for specific symptom profiles. While clinical trials with immunomodulatory therapies have shown significant e.g.: cognitive improvements the underlying mechanisms remain unclear, limiting personalized treatments. For the first time, this study integrates neuroinflammatory biomarkers, FC alterations, and behavioral symptoms of Psychosis in one framework. Using data from the Human Connectome Project for Early Psychosis (HCP-EP), FC and network-metrics like integration and segregation were derived from minimally preprocessed fMRI data, while brain simulation-based metrics were computed using the neuroinformatics platform The Virtual Brain (TVB: www.thevirtualbrain.org) . Symptoms were assessed using a comprehensive set of questionnaires, including PANSS and WASI-II. Our Findings demonstrate that inflammatory biomarkers significantly predict symptom severity, with FC changes acting as relevant mediators. The results shed light on the question which psychotic symptoms are closely related to inflammatory processes providing potential targets for immunomodulatory therapies. This approach may also enhance our understanding of Psychosis as a concept, adding to a growing body of evidence suggesting different mechanisms underlying this one diagnostic label.

Topic Area: OTHER