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Central Institute of Mental Health

The Central Institute of Mental Health (Zentralinstitut für Seelische Gesundheit) in Mannheim, Germany, is a leading psychiatric research institution affiliated with Heidelberg University. It specializes in research, treatment, and education related to mental health disorders, neuroscience, and psychosocial factors influencing mental well-being. The institute plays a crucial role in advancing psychiatric knowledge and developing innovative therapies through interdisciplinary collaboration and state-of-the-art facilities.

ZI Innengarten
Building of the Central Institute of Mental Health(ZI) in Mannheim ©ZI

Contributors

Gabriele Ende

A03: Modulation of aggression by acute threat A08: The metabolic lung-brain axis in aggressive behavior in patients with AMD Q02: Data management for computational modelling Principal investigator Quality control group member Research data committee member Central Institute of Mental Health

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.

Andreas Meyer-Lindenberg

A05: Peripersonal space violations and social threat: daily-life psychological and neural mechanisms of environmental risk for reactive aggression A06: Decoding dynamic reciprocal neural mechanism underlying reactive aggression: Insights from fMRI and fNIRS hyperscanning B04: Investigating psychological and neural correlates of intimate partner violence Principal investigator Heidelberg University Central Institute of Mental Health

Andreas Meyer-Lindenberg is a distinguished psychiatrist and neuroscientist based in Germany, renowned for his groundbreaking research on the neurobiological underpinnings of psychiatric disorders. He serves as the Director of the Central Institute of Mental Health (ZI) in Mannheim and is a professor at the University of Heidelberg. Meyer-Lindenberg’s work focuses on understanding how genetic and environmental factors influence brain function and contribute to mental illnesses such as schizophrenia and depression. His contributions have significantly advanced the field of psychiatric neuroscience, providing deeper insights into the mechanisms of mental health disorders and informing the development of more effective treatments.

Projects

A03: Modulation of aggression by acute threat

Gabriele Ende Christian Schmahl Central Institute of Mental Health Negative valence system Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
The neural and neurochemical patterns of acute threat as modulators of aggression in BPD will be investigated in this project. The modulation of aggressive responses under acute threat is induced by the threat-of-shock paradigm. The main translational research question is if and how aggressive responses are modulated by threat, and which neurofunctional and neurochemical patterns underlie these responses during safe and threat conditions. MR spectroscopy will be used in patients to assess glutamate and GABA levels. In a further translational approach, the least and the most aggressive/impulsive recombinant inbred mouse lines identified in C01 in Frankfurt will be tested in Mannheim with animal MR spectroscopy at 9.4T to determine the relationship between glutamate, GABA, impulsivity, and aggression in these mouse lines as well as in comparable brain regions assessing neurofunctional and neurochemical patterns.

A05: Peripersonal space violations and social threat: daily-life psychological and neural mechanisms of environmental risk for reactive aggression

Heike Tost Andreas Meyer-Lindenberg Central Institute of Mental Health Negative valence system Human Cognitive and Systems Neuroscience Biological Psychiatry
Peripersonal space, the representation of the space immediately surrounding the body, will be studied as an underlying factor for threat experience. Early-life stressors and daily-life stressors will be tested as factors influencing PPS processing and associated specific brain activation patterns. Location tracking and geoinformatics mapping, virtual reality (VR) experiments, physiological stress markers, and brain function during the processing of PPS violations in healthy at- risk individuals will be used to identify predictive biomarkers related to psychiatric risk, enhanced neural behavioral sensitivity to PPS interference and reactive aggression in daily life.

A06: Decoding dynamic reciprocal neural mechanism underlying reactive aggression: Insights from fMRI and fNIRS hyperscanning

Kerstin Konrad Andreas Meyer-Lindenberg Vanessa Reindl RWTH Aachen Central Institute of Mental Health Negative valence system Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
The project employs fMRI and functional near-infrared spectroscopy (fNIRS) hyperscanning techniques to explore how brain-to-brain synchrony and dynamic processes within peer dyads facilitate or inhibit aggressive behavior under diverse levels of provocation in adolescent patients and controls. In two fully interactive tasks, we will probe aggressive behavior towards a task partner, and quantify the building of interpersonal trust/distrust applying a social interaction and economic exchange paradigm. These paradigms will be employed within dyads in fMRI hyperscanning settings and extended by group-based fNIRS methods in triads to study effects of peers, social exclusion, and coalitions on aggressive behavior in semi-naturalistic interactions. Between-brain neural synchrony will be computed and related to everyday social experiences and individual predispositions to identify markers for the prediction of aggressive behavior.

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

Thomas Frodl David Slattery Gabriele Ende RWTH Aachen Goethe University Frankfurt Central Institute of Mental Health Negative valence system Biological Psychiatry Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
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.

B03: A process-based brain-computer interface to modulate aggressive behavior – a real-time fMRI neurofeedback study

Klaus Mathiak Christian Paret-Voigt Jana Zweerings RWTH Aachen Central Institute of Mental Health Cognitive system Biological Psychiatry
Probe the self-regulation of CS networks in adults and adolescents diagnosed with mental disorders related to frequent stress-associated affective outbursts and aggressive symptoms in posttraumatic stress disorder (PTSD), and BPD. The patients will subsequently be trained to regulate the frontal control network to varying acute threat in a double-blind, randomized, controlled design. An immersive, virtual brain- computer-interface (BCI) will allow for a culture- and age-sensitive, personalized training approach. The aim of the present investigation is to assess feasibility of the approach according to four clinical markers: Reduction of perceived threat and aggressive behavior in daily life, improved control in the face of unfair provocation, and neurofeedback-specific modulation of the neural networks.

B04: Investigating psychological and neural correlates of intimate partner violence

Lisa Wagels Andreas Meyer-Lindenberg Katja Bertsch Julia Koch Julia Schräder Linda Wilkin-Krug RWTH Aachen Central Institute of Mental Health Julius-Maximilians University Würzburg Cognitive system Biological Psychiatry Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Focus on the neural correlates of characterizing cognitive control deficits during conflict situations. The project will investigate patients with varying levels of cognitive control along with their close partners (sibling or intimate partner) to identify the dynamics of self-regulation and co-regulation in provoked conflict situations in patients with control deficits. To identify the precursors and dynamics of conflict escalation, the project will apply measures of behavioral reactions, skin conductance, simulated or real conflict, fMRI and fMRI-hyperscanning techniques and physiological measures. Neuroimaging data will also be combined with information on stress, control and conflicts in real-life via EMA.

B05: Predictors and (neuro-)biological correlates of (cyber-)bullying and victimization in real-life contexts

Nathalie Holz Tobias Banaschewski Central Institute of Mental Health Cognitive system Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Focus on the investigation of a lack of cognitive control in bullies and victims that contributes to the risk of developing mental health problems. Therefore, the project will assess bullies and their victims in real-life and digital social interactions to investigate how aberrant cognitive and affective prefrontal control and sensitivity to peer rejection with accompanied alterations in autonomic arousal may increase externalizing and internalizing behavior. To this end, a unique combination of ambulatory assessments of (cyber-)bullying, functional neuroimaging (emotion regulation, inhibition, social exclusion), physiological assessments (heart rate variability) and clinical trait-related questionnaires will be applied. Decoding dynamic

C03: Distributed network control and interventions to frustrative non-reward and threat triggered aggressions

Wolfgang Kelsch Wolfgang Weber-Fahr Johannes Gutenberg University Mainz Central Institute of Mental Health Interaction of negative valence system and cognitive system Biological Psychiatry Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Investigate context-dependent aggression triggered by frustrative non-reward or acute social threats. Using newly developed approaches, multiple behavioral domains will be assessed in a semi-naturalistic, autonomous mouse habitat. Specifically, the habitat assesses the inter-individual dynamics of social interactions, aggressions, and hierarchy and the individual reward learning and impulsivity through different integrated modules. Intermittent challenges comprise intruder aggression and frustrative non-rewards. Within this LCD, circuit mechanisms are dissected through chemogenetic interventions, in vivo recordings, and functional MRI in awake mice during task performance. This approach in the first funding period will enable us to disentangle the specific functions of candidate entry points in prefrontal to ventral striatum pathways with respect to their modulation of aggression and dominance for potential interventions.

Q02: Data management for computational modelling

Michael Hanke Gabriele Ende Richard Nkrumah Christine Ecker Klaus Mathiak Wiebke Hennig Arezoo Taebi Service project Research Center Jülich (FZJ) Central Institute of Mental Health Goethe University Frankfurt RWTH Aachen
Data management and training platform. A decentralized data management infrastructure will help focus on developmental and therapeutic longitudinal data, training all participating researchers in the necessary skills for future use. This strategy will lay the foundations for further data-driven computational modelling projects in the next funding period.

This is a distributed project, with representatives at all main TRR379 sites.