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A08: The metabolic lung-brain axis in aggressive behavior in patients with AMD

Beta-hydroxy-butyrate (BHB), a ketone body, is negatively associated with aggressive behavior. BHB is a metabolite and an active signaling substrate involved in epigenetic regulation of e.g., neurotrophic factor genes in the brain. Of the three main ketone bodies, acetone, acetoacetate and BHB, acetone is a very volatile compound, mainly eliminated through respiration, thus can be measured non-invasively in breath. A reduction of acetone in breath has been found to highly correlate with BHB in blood and be associated with symptom severity in schizophrenia (Jiang et al. 2022). Using MR spectroscopy, A08 aims to (1) identify whether acetone and other volatile organic compounds in breath are associated with aggression and acute threat processing in mental disorders and (2) to examine whether these breath markers are associated with direct metabolic brain correlates (like BHB, glutamate) and with the brain-derived neurotrophic factor (BDNF) levels in plasma. In a translational approach, (3) we will test if supplementation of BHB reduces aggressive behavior in mice.

Contributors


Gabriele Ende

Gabriele Ende is a researcher associated with the Central Institute of Mental Health (ZI) in Mannheim, Germany. Her work primarily focuses on neuroimaging and the application of magnetic resonance spectroscopy (MRS) in psychiatric and neurological disorders. Ende’s research aims to deepen the understanding of brain chemistry and its alterations in various mental health conditions.

Thomas Frodl

Thomas Frodl is a prominent neuroscientist and psychiatrist affiliated with RWTH Aachen University in Germany. His research focuses on the neurobiological underpinnings of psychiatric disorders, particularly depression and anxiety. Frodl employs advanced neuroimaging techniques to investigate brain structure and function, aiming to understand the mechanisms that contribute to these conditions. His work is instrumental in developing more effective diagnostic and therapeutic strategies, bridging the gap between clinical practice and neuroscience research.

David Slattery

Professor David Slattery is interested in understanding of the neurobiology and treatment of stress-related disorders; with an emphasis on mood and anxiety disorders. A particular focus is the study postpartum mood and anxiety disorders using stress- and diet-based models in rodents, as well as:

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A mechanism-based group psychotherapy approach to aggressive behavior (MAAP) in borderline personality disorder: a multicenter randomized controlled clinical trial

High levels of trait anger and aggressive behavior are common and problematic phenomena in patients with borderline personality disorder (BPD). In BPD, patterns of reactive aggression often lead to functional impairment affecting important areas of life. Despite the high burden on individuals and their social environment, there are no specific, cost-effective treatments to reduce aggression in BPD. In previous studies, we and others have been able to infer specific biobehavioral mechanisms underlying patterns of reactive aggression in BPD that can be used as potential treatment targets. To address this, we developed a mechanism-based anti-aggression psychotherapy (MAAP) for the group setting that specifically targets the biobehavioral mechanisms underlying outward-directed aggression in BPD. A previously conducted proof-of-concept study had suggested beneficial effects for this neglected group of patients. In this multicenter, confirmatory, randomized-controlled-clinical-trial, MAAP, which consists of multifaceted, evidence-based treatment elements adapted from other sophisticated treatment programs such as Dialectical Behavior Therapy and Mentalization-Based Treatment, is tested for efficacy against a non-specific supportive psychotherapy (NSSP) program focusing on non-specific general factors of psychotherapy at seven different sites in Germany. Both treatment arms, based on one individual and 13 group therapeutic sessions (1.5 h per session, twice a week), are delivered over a period of 7–10 weeks. A total of N = 186 patients will be recruited, half of whom will be cluster-randomized to MAAP. Outcomes are assessed at baseline, immediately, and 4, 12, 20, and 24 weeks post-treatment using ecological momentary assessment, clinical interviews, questionnaires, and online tasks. If proven superior, MAAP can be incorporated into standard psychiatric care, filling a critical gap in the current therapeutic landscape by offering a structured, cost-effective, and evidence-based treatment that directly targets the biobehavioral mechanisms underlying reactive aggression in BPD. By potentially improving clinical outcomes and reducing the burden of reactive aggression in BPD, MAAP could be beneficial for both individuals and their social environments. The study’s large, multicenter design enhances the generalizability of the results, making them more relevant for broader clinical applications.