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Goethe University Frankfurt

Goethe University Frankfurt is known for its strong emphasis on research across diverse fields, including social sciences, humanities, and natural sciences. The university fosters a dynamic academic environment with a commitment to academic freedom and a focus on societal relevance and innovation.

Eingansgsbereich der Psychiatrie in Frankfurt
Welcome area at the Department of Psychiatry ©University of Frankfurt
Therapieraum der Psychiatrie in Frankfurt
Therapy at Department of Psychiatry ©University of Frankfurt

Contributors

Andreas G. Chiocchetti

C04: The sex-specific role of genes, early adversity, peers, community violence, and puberty related endocrinological changes in adolescent pathological aggression Equal opportunity committee member Principal investigator Goethe University Frankfurt

Professor Andreas G Chiocchetti is passionate about working with models to understand human behaviour and neurodiversity. Biotechnologist by training (Salzburg, Austria), Phd in Genetics, Research Fellow at UCLA, Los Angeles, ex Data-Scientist in Industry. Member of the Equal Opportunity and Diversity working group at the TRR379.

Christine Ecker

C05: The neuroanatomical underpinnings of clinical aggression and their relationship with the negative valence and cognitive control systems Q02: Data management for computational modelling Principal investigator Research data committee member Goethe University Frankfurt

Christine Ecker is a professor at Goethe University Frankfurt, specializing in clinical neuroscience and psychiatry. Her research focuses on the neurobiological underpinnings of autism spectrum disorders and other neurodevelopmental conditions, utilizing advanced neuroimaging techniques. Ecker’s work aims to bridge the gap between clinical practice and neuroscience to improve diagnostic and therapeutic strategies for these disorders.

Christine Margarete Freitag

C04: The sex-specific role of genes, early adversity, peers, community violence, and puberty related endocrinological changes in adolescent pathological aggression Q01: Recruitment and biotyping transdiagnostic risk mechanisms for aggressive behaviors in mental disorders across the life span Principal investigator Goethe University Frankfurt

Professor Christine M Freitag focuses on Translational research in Neurodevelopmental, Anxiety and Disruptive Behavior Disorders in children and youth. Her methods comprise biostatistics, diagnostic and biomarker studies, randomized-controlled trials (phase-IIa, phase-III), brain stimulation and behavioural/psychotherapeutic interventions.

Andreas Reif

A07: The intestinal microbiota as a regulator of aggressive and impulsive behavior B01: Neurobehavioral effects of repetitive prefrontal transcranial direct current stimulation (tDCS) on pathological aggression Q01: Recruitment and biotyping transdiagnostic risk mechanisms for aggressive behaviors in mental disorders across the life span Citizen Advisory Board Deputy-Spokesperson Management board member Principal investigator Steering committee member Goethe University Frankfurt

Andreas Reif is a German Psychiatrist, who received his training at the University Hospital Würzburg, where he also did his residency and later on became Vice Chair. In 2014, he took over the position of Chair of the Department of Psychiatry, Psychosomatic Medicine and Psychotherapy at the University Medical Center Frankfurt, where he is also full professor. ARs clinical and research interests include affective disorders (TRD, bipolar disorder, suicidality) and adult ADHD; his research is translational in nature and revolves around the ideas of precision psychiatry, i.e. identifying the best therapy at the exact time for a given individual patient. He has published more than 650 original papers and reviews, also in the most prestigious journals such a the New England Journal of Medicine, Lancet and Science, and has an h² index of 97. He is an internationally renowned speaker and active in several learned societies, especially the German Psychiatric Association (DGPPN), where he is an executive board member, as well as ECNP, where he is president elect. Also, he is involved in several clinical guidelines and outreach programs.

David Slattery

A07: The intestinal microbiota as a regulator of aggressive and impulsive behavior A08: The metabolic lung-brain axis in aggressive behavior in patients with AMD 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 Q03: Integrated Research Training Group (RTG) Citizen Advisory Board Principal investigator Public relations team member Research training group (RTG) committee member Goethe University Frankfurt

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:nn– The role of neuropeptides in anxiety- and affective- disordersn– The molecular basis of Social Anxiety Disorder and the assessment of novel treatment options n– Sex- differences in the aetiology and treatment of stress-related disorders.

Projects

A07: The intestinal microbiota as a regulator of aggressive and impulsive behavior

David Slattery Andreas Reif Goethe University Frankfurt Negative valence system Biological Psychiatry
This translational project investigates sex-dependent behavioral effects of faecal microbiota transplantation to microbiome-depleted mice from AMD patients (selected based on their aggressive and impulsive traits from Q01), as well as healthy controls. Impulsivity will be assessed via the continuous performance test and responses towards acute threat via the escalated resident intruder test. The goal is to determine the sex-dependent effects of faecal transplantation on selected readouts involved in the transfer of the patient’s phenotype to the mice, such as immune parameters, sex hormones, neuronal activity (and morphology, e.g., neurite outgrowth, spines, etc.), and gene expression (e.g., Rbfox1 from prior studies and novel candidates from C01 and C04).

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.

B01: Neurobehavioral effects of repetitive prefrontal transcranial direct current stimulation (tDCS) on pathological aggression

Carmen Weidler Andreas Reif RWTH Aachen Goethe University Frankfurt Cognitive system Biological Psychiatry Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
TDCS will be used as an interventional tool to decrease aggression. Using a simultaneous tDCS – fMRI approach, the project aims to enhance cognitive control by repeated prefrontal brain stimulation, investigating its effect on aggression. In addition to gauging tDCS responsivity, identifying the role of individual factors such as genetic profiles in aggression will be a particular focus of this project. By examining brain activity at multiple time points (e.g., before, during multiple stimulation sessions and after tDCS), it will add to the understanding of mechanisms underlying neural tDCS effects and help to identify individual factors that predict responsiveness to the stimulation. To determine the therapeutic potential, we will include psychiatric patients with substance use problems, a group of criminal, violent offenders, and healthy matched controls.

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

Aet O'Leary David Slattery Goethe University Frankfurt Interaction of negative valence system and cognitive system Biological Psychiatry
Sex-dependent effects and gene-environment interactions will be investigated by applying escalating aggression paradigms. Specifically, the project will investigate the effects of early life stress on aggression in response to threat and hyperactivity as well as social decision-making in 32 BXD mouse strains, the progenitor strains (C057Bl/6J and DBA/2J), and the F1 BXD cross. The project aims to identify the quantitative trait loci (QTL) and putative candidate genes contained within the QTL and associate them with specific behavioral responses of stressed and unstressed cohorts of mice. The publicly available database GeneNetwork (www.genenetwork.org) will be used to validate the findings which include measurements of mRNA and protein expression, and methylation patterns in mouse brains

C04: The sex-specific role of genes, early adversity, peers, community violence, and puberty related endocrinological changes in adolescent pathological aggression

Christine Margarete Freitag Andreas G. Chiocchetti Goethe University Frankfurt Interaction of negative valence system and cognitive system Biological Psychiatry Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Address sex-specific NVS (reactive aggression) and CS (different dimensions of psychopathy, proactive aggression) associated risk factors, and risk factor-based biosignatures in young people. Considering the interacting genetic, environmental, and hormonal factors related to these specific aggressive behavior dimensions, C04 will identify specific and shared factors and mechanisms related to NVS and CS in female and male youth with and without pathological aggression. Implementing deep-learning algorithms, sex-specific, data-driven subgroups in relation to dimensions of aggressive behavior will be described and probed against the NVS and CS. Group-level risk factors of aggressive behavior dimensions, and individual risk factor-based subgrouping will be the basis of developing a biologically informed stratification strategy for tailored treatment. Models and classifiers will be established cross-sectionally in available data and replicated in the prospectively collected cross-sectional data (Q01). In addition, C04 will test the models and classifiers for predictive validity in the longitudinal data of the TRR Q01 cohort.

C05: The neuroanatomical underpinnings of clinical aggression and their relationship with the negative valence and cognitive control systems

Christine Ecker Goethe University Frankfurt Interaction of negative valence system and cognitive system Biological Psychiatry
Link questionnaire measures of aggression to specific neural substrates using structural MRI. The resulting patterns of aggression-related neuroanatomical variability will be co- registered with the Allen Human Brain Atlas providing gene-expression data, to highlight genes with a spatial pattern of expression that matches the neuroimaging findings. Utilizing the neurotypical control data, a normative model of neuroanatomical diversity within the NVS and CS will be established to quantify neuroanatomical abnormalities within these systems in individual cases

C07: Identifying mediators of threat-aggression and experimental manipulation by tDCS

Michael Plichta Wolfgang Retz Goethe University Frankfurt Johannes Gutenberg University Mainz Interaction of negative valence system and cognitive system Biological Psychiatry
Test the interaction of the CS and frustrative non-reward as part of the NVS. It will investigate the electrophysiological correlates of frustrative feedback in aggression-prone patients. In the aftermath of induced stress, an EEG task-battery including frustrative feedback will be applied for extraction of error-related negativity (ERN) and contingent negative variation to monitor electro-physiologic signaling of the relevant learning and frustration processes. In half of the participants, tDCS over the prefrontal cortex will be applied to enhance cognitive control, with participants being put into a stress context inducing frustration.

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.