What is A08 about

We would love to take you on a journey through our project. Please find here a video explaining a bit about the subproject “A08: The metabolic lung-brain axis in aggressive behavior in patients with AMD”

Aggressive behavior can often be traced to situations where individuals feel threatened. This project investigates potential associations between metabolic substrates and aggression to shed light on biological causes and provide pathways for treating patients.

Beta-hydroxy-butyrate (BHB), a ketone body, is negatively associated with aggressive behavior. BHB is both a metabolite and an active signaling substrate involved in epigenetic regulation of neurotrophic factor genes in the brain. Of the three main ketone bodies (acetone, acetoacetate, and BHB), acetone is a volatile compound that can be measured non-invasively in breath. This project marks the first investigation of metabolomics of aggression in psychiatric cohorts.

Using MR spectroscopy and breath gas sampling, A08 examines whether acetone and other volatile organic compounds in breath are associated with aggression and acute threat processing in mental disorders. The project will analyze direct metabolic brain correlates (BHB, glutamate) in brain regions associated with aggression—the anterior cingulate cortex and orbital frontal cortex—and their relationship to brain-derived neurotrophic factor (BDNF) levels in plasma.

The study involves three sites:

• RWTH Aachen University Hospital: 120 patients (50% with affective and anxiety-related mental disorders) and 60 healthy participants undergo clinical investigation, breath VOC sampling, blood analysis, and 7 Tesla MRI scans
• Central Institute of Mental Health Mannheim: 30 controls are scanned to establish protocols for detecting dynamic BHB changes during acute threat tasks
• Goethe University Medical Center Frankfurt: Translational mouse studies test whether BHB supplementation reduces aggressive behavior in controlled experimental settings