Conference Agenda

Aggression is frequent transdiagnostic phenomenon in mental disorders. Despite receiving a constantly high interest in public media, still little is known about the neuropsychobiological underpinnings of aggression in mental disorders and how this knowledge can be used to improve prediction, prevention, and treatment. The new transregio SFB 379 „Neuropsychobiology of Agression: a Transdiagnostic Approach in Mental Disorders“ aims at addressing these issues by combining innovative experimental neurobiological studies with prospective assessments in a large transdiagnostic sample of adolescents and adults. In this symposium, we will first introduce the research consortium’s concept and primary goals (Katja Bertsch, JMU Würzburg) and then present existing data from ongoing studies of the partner sites. These presentations include a talk by Ke Chen (ZI Mannheim) who will speak about lifespan normative modelling of aggression and individual risk profiling. Following this, Lisa Wagels (RWTH Aachen) will present transdiagnostic data of anger, hostility and aggression and Kornelius Kammler-Sücker & Christoph Korn (ZI Mannheim, University Hospital Heidelberg) will introduce a novel VR and online aggression learning paradigm eliciting anger. Finally, Nadine Steinbach (PhD student from University Hospital Frankfurt) will talk about the identification of mediators of threat-aggression and experimental manipulation by tDCS.

Aggression is an evolutionary preserved behaviour, which includes the harm of another living being to protect, gain or defend something of value. Aggression is conceptualized as a multifactorial phenomenon. Complex neurocognitive and neurobiological pathways are assumed to mediate the multiple manifestations and thereby define aggressive biotypes. Many mental disorders are associated with an increased likelihood for aggression. In addition to the enorous negative social, socio-economic, and personal consequences, aggressive behavior in patients worsens treatment outcome. The transregio SFB 379 (TRR 379) "Neuropsychobiology of Aggression" aims at advancing our understanding of neurocognitive and neurobiological mechanisms and situational/environmental influences determining specfic behavioral patterns of aggression in mental disorders. In this introductory talk, the aims, structure, and methods of the TRR 379 will be presented to set the grounf for the following talks in which empirical data will be presented.

Aims: Aggression varies across age and sex, yet there is a lack of studies utilizing large datasets to model aggression across the lifespan. This research aims to construct normative models of aggression and investigate risk factors linked to individual extreme aggression deviations.

Methods: Using data from both publicly available datasets and in-house datasets including for instance at risk-cohorts such as MARS and clinical cohorts such as Aggressotype, we will analyse data from approximately 26,000 individuals aged 5 to 70. Aggression levels, assessed through both self-reported and other-reported measures, will be modelled using warped Bayesian linear regression to capture age-related trajectories. Individuals showing extreme deviations from normative patterns will be profiled based on risk factors identified in previous research.

Results and Conclusions: Initial analyses indicate a decline in aggression from ages 5 to 10 in both sexes, with stability during adulthood. Males showed a slight increasing aggression trend after age 55. Ongoing analysis will be focused on refining the models and characterizing individuals with pronounced deviations to undercover their risk patterns. This study may enhance the understanding of aggression development across the lifespan and may provide insights on early identification and targeted interventions for high-risk individuals.

An important influencing factor for more frequent or intense aggression is the presence of a disease. Especially mental disorders are associated with heighted aggression. Additionally, side effects of medication may increase aggressiveness, e.g. in patients with epilepsy. Clinicians observed increased aggression for anti-epileptic drugs such as Levetiracetam, Breivaracetam, and Perampanel.

Two studies on aggression in patient groups will be presented. In study one, patients with major depression (MDD), schizophrenia (SCZ), substance use disorder (SUD), personality disorder (PD), and healthy controls conducted three aggression tasks, reported about their emotions, and answered questionnaires on personality traits. In study two, patients with epilepsy who were taking either Levetiracetam, Brivaracetam, or Perampanel conducted the same paradigms in a 3 Tesla scanner assessing functional brain images.

Patients with mental disorders reported higher aggression and impulsivity than controls. Behaviorally, mixed results showed enhanced reactivity towards social provocation in PD and overall enhanced aggression in SUD; MDD and SCZ reacted similarly as healthy controls. In the non-social provocation task, SCZ showed more blunted reactions towards provocation. Patients with epilepsy showed similar responses towards social and non-social provocation as controls, but brain activity during low and medium provocation was increased and patients showed a tendency towards reporting trait aggression.

The studies show that aggression should be investigated as a multifaceted construct as behavioral and self-report data deviated in patient groups. The data on epilepsy patients does not support a heightened aggression level towards provocation. Both studies highlight that self-descriptions of patients are more negative compared to controls.

Aggression is a severe obstacle to joint success in social interactions. We developed a novel social learning task which measures aggression in the form of an active refusal of cooperation. This paradigm allows for the variation of multiple parameters like the computer player’s strategy and extends current PC environments by using immersive virtual reality (VR) which increases immersion and enables standardized yet engaging interactions with life-sized human-like avatars and even personalized doppelgangers. Participants interact with several virtual agents on grids to reach goals. Agents have distinct strategies to be either cooperative or competitive and participants’ starting positions on the grid are advantageous or disadvantageous for them. After each interaction, participants rate their anger about the agent. Two studies using an abstract online version (N = 30) and an immersive VR version (N = 57) yielded consistent results. Participants’ cooperation in the last trial of an interaction depended on the agent strategy in the previous trials. Participants cooperated less with competitive than with cooperative agents – an indicator of social learning and reactive aggression considering that cooperation is not costly in the paradigm. Accordingly, anger ratings for competitive agents were higher than for cooperative agents. Additionally, physiological data (heart rate, respiratory rate, and eye tracking) was collected during the VR study and might provide further insights. In order to test reactions to non-cooperation, we have developed a new task that can be administered in a online and a VR version.

Aggression is not only a major societal issue but also a common symptom in mental disorders such as ADHD and bipolar disorder (BD). Despite existing treatments, the demand for more precise, efficient and low-risk alternatives remains high. One promising option could be transcranial direct current stimulation (tDCS). Since acute stress increases the risk of aggression in aggression-prone individuals, we aim to explore the modulatory effects of cognitive control (CC) and negative valence (NV) in shaping aggressive responses. To this end, participants will undergo the stress-inducing Socially Evaluated Cold Pressor Test (SECPT), followed by comprehensive assessments of stress and aggression. Furthermore, an EEG task battery – including the Eriksen Flanker Task and the Monetary Incentive Delay Task – will measure event-related potentials linked to CC and frustrative non-reward (FNR), specifically error-related negativity (ERN), cue-P3, contingent negative variation (CNV) and feedback-related negativity (FRN). In 50% of participants, tDCS will be applied to determine whether aggression can be reduced by directly enhancing CC or by decreasing FRN as a secondary effect of improved top-down control.