TRR 379:  Neuropsychobiology of Aggression: A Transdiagnostic Approach in Mental Disorders

• Subject Area: Medicine ; Biology ; Social and Behavioural Sciences
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 512007073

The proposed initiative unites major German sites with expertise in neurobiological and clinical aggression research in a joint endeavor to advance knowledge on the biological bases of aggression in mental disorders (AMD) and its developmental course. Acknowledging the complexity of this clinical construct, this Transregional Collaborative Research Center (TRR) will follow the Research Domain Criteria (RDoC) framework, investigating multiple aspects that characterize aggression: genetic, molecular mechanisms, hormonal, neural and associated behavioral systems. Thus, the TRR aims to identify biosignatures of AMD based on multidimensional pathways that underlie the different manifestations of aggression to enable the development of tailor-made biosignature-specific prevention and intervention. It will follow three overarching objectives: First, the TRR proposes to investigate AMD in a transdiagnostic manner and within the RDoC’s "negative valence system" (NVS) and "cognitive system" (CS) to identify and characterize specific biosignatures and predict aggressive behavior. Both domains are integral to aggression and are negatively affected in mental disorders. The TRR integrates projects probing threat and frustration processing (i.e., NVS) and cognitive control (as part of the CS), both independently and in their interaction. Second, the TRR will seek to identify and define these mechanisms on a multilevel scale, advancing a detailed understanding of the biology, psychology, and physiology of specific aggressive biosignatures across mental disorders. To this end, we propose to translationally investigate biological mechanisms via animal models as well as modulatory and mediating factors in humans. The third, and final objective is to address the temporal stability of AMD and the (dys-)functional NVS and CS during development from early adolescence until adulthood and during the disease course. The clinical, longitudinal and developmental approach, together with a large dataset offer attractive perspectives for the next funding phases into therapeutic and predictive as well as societal directions. Along with the establishment of a longitudinal cohort design (LCD) across different mental disorders, we will model the trajectories of aggressive biosignatures and their correlation to NVS/CS characteristics as well as psychopathological changes. Such longitudinal studies are crucial to disentangle the interplay between the organism and environment, especially with regard to critical periods and windows of prevention opportunity. The unique competence and interdisciplinary collaboration of the TRR members will provide the basis for an overall strategy in which experimental concepts in animals and humans coincide and dovetail to address our three main objectives. Only through such an interdisciplinary multilevel approach, based on long-standing collaborations, can we address AMD in ist complexity to the benefit of patients and society.

• DFG Programme: CRC/Transregios

Current projects

• A01 - The neural code of stimulus-triggered territorial aggression (Project Head Spehr, Marc )
• A02 - Context effects on threat processing in dependence of testosterone levels (Project Heads Bertsch, Ph.D., Katja ;  Habel, Ute ;  Herpertz, Sabine C. )
• A03 - Modulation of aggression by acute threat (Project Heads Ende, Gabriele ;  Schmahl, Christian )
• A04 - Implicit chemosensory threat signals as stimulators of amygdala hyperresponsiveness in AMD (Project Heads Chechko, Natalya ;  Habel, Ute )
• A05 - Peripersonal space violations and social threat: daily life psychological and neural mechanisms of environmental risk for reactive aggression (Project Heads Meyer-Lindenberg, Andreas ;  Tost, Heike )
• A06 - Decoding dynamic reciprocal neural mechanism underlying reactive aggression: Insights from fMRI and fNIRS hyperscanning (Project Heads Konrad, Kerstin ;  Meyer-Lindenberg, Andreas ;  Reindl, Vanessa )
• A07 - The intestinal microbiota as a regulator of aggressive and impulsive behavior (Project Heads Reif, Andreas ;  Slattery, Ph.D., David )
• A08 - The metabolic lung-brain axis in aggressive behavior in patients with AMD (Project Heads Ende, Gabriele ;  Frodl, Thomas ;  Slattery, Ph.D., David )
• B01 - Neurobehavioral effects of repetitive prefrontal transcranial direct current stimulation (tDCS) on pathological aggression (Project Heads Reif, Andreas ;  Weidler, Carmen )
• B02 - Young offenders’ self-regulation deficit as a common mechanism for aggressive behavior and psychopathology - neural mechanisms and role of adverse childhood experiences (Project Heads Retz, Wolfgang ;  Tüscher, Oliver )
• B03 - A process-based brain-computer interface to modulate aggressive behavior – a real-time fMRI neurofeedback study (Project Heads Mathiak, Klaus ;  Paret, Christian ;  Zweerings, Jana )
• B04 - Investigating psychological and neural correlates of intimate partner violence (Project Heads Bertsch, Ph.D., Katja ;  Meyer-Lindenberg, Andreas ;  Wagels, Lisa )
• B05 - Predictors and (neuro-)biological correlates of (cyber-)bullying and victimization in real-life contexts (Project Heads Banaschewski, Tobias ;  Holz, Nathalie )
• C01 - Gene-environment interactions and the role of impulsivity in responding to acute threats: early-life stress and escalated aggression in recombinant inbred mouse strains (Project Heads O' Leary, Ph.D., Aet ;  Slattery, Ph.D., David )
• C02 - Aggressive decisions in social conflicts – Neuro-cognitive models for healthy individuals and psychiatric patients with high scores of aggression (Project Heads Korn, Christoph ;  Mathiak, Klaus )
• C03 - Distributed network control and interventions to frustrative non-reward and threat triggered aggressions (Project Heads Kelsch, Wolfgang ;  Weber-Fahr, Wolfgang )
• C04 - The sex-specific role of genes, early adversity, peers, community violence, and puberty related endocrinological changes in adolescent pathological aggression (Project Heads Chiocchetti, Ph.D., Andreas G. ;  Freitag, Christine Margarete )
• C05 - The neuroanatomical underpinnings of clinical aggression and their relationship with the negative valence and cognitive control systems (Project Head Ecker, Ph.D., Christine )
• C06 - Brain mechanisms differentiating aggressive vs. non-aggressive psychopathology as sequelae of early life maltreatment (Project Heads Herpertz, Sabine C. ;  Neukel, Corinne )
• C07 - Identifying mediators of threat-aggression and experimental manipulation by tDCS (Project Heads Plichta, Michael ;  Retz, Wolfgang )
• Q01 - Identification of Aggression Biosignatures in AMD (Project Heads Banaschewski, Tobias ;  Freitag, Christine Margarete ;  Frodl, Thomas ;  Habel, Ute ;  Herpertz, Sabine C. ;  Konrad, Kerstin ;  Reif, Andreas )
• Q02 - Data Management and Training Platform for AMD Research (Project Heads Ecker, Ph.D., Christine ;  Ende, Gabriele ;  Hanke, Michael ;  Mathiak, Klaus )
• Q03 - Research Training Group for Interdisciplinary Scientists in AMD (Project Heads Banaschewski, Tobias ;  Slattery, Ph.D., David ;  Wagels, Lisa )
• Q04 - Governance and Scientific Communication in AMD Research (Project Head Habel, Ute )

• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Co-Applicant Institution: Goethe-Universität Frankfurt am Main; Ruprecht-Karls-Universität Heidelberg
• Participating University: Johannes Gutenberg-Universität Mainz; Julius-Maximilians-Universität Würzburg
• Participating Institution: Forschungszentrum Jülich
• Spokesperson: Professorin Dr. Ute Habel