Holz N. DFG - Deutsche Forschungsgemeinschaft HO 5674/4-1: Mehrdimensionale Modellierung von Resilienz und Vulnerabilität gegenüber Psychopathologie. 10/2025-09/2028.
Encountering environmental adversities may increase the risk of developing psychiatric disorders. Yet the mechanisms underlying why some individuals develop psychopathology while others do not remain unclear. This is also attributable to the lack of established markers to quantify vulnerability and resilience. Our research project aims to fill this gap by exploring and modelling the heterogeneous responses individuals have to adverse experiences and uncovering the neurobiological mechanisms at play. We plan to achieve this by leveraging large data cohorts and employing advanced deep learning technologies. Specifically, our modeling framework will: i) map mental health outcomes to adversity using a normative model to clarify the relationship between adversity and mental health, ii) identify individual risk and resilience markers by quantifying deviations from this normative model, iii) integrate these deviations with multimodal brain features to uncover underlying mechanisms and biomarkers. This approach enables the mapping of individual markers of extreme resilience and risk across psychiatric disorders, marking a crucial step towards precision medicine in psychiatry.
Holz N. MWK - Ministerium für Wissenschaft Forschung und Kunst Baden-Württemberg Sonderfördermaßnahme COVID-19 Forschung: The impact of Covid-19 on mental health: Longitudinal evidence for prädiktive socioenvironmental and neurobehavioral risk and resilience patterns . 07/2020-06/2021.
Holz N. DFG - Deutsche Forschungsgemeinschaft HO 5674/2-1: Exploring the long-term impact of early life adversity on the (anti-)social brain”. 04/2018-04/2021.
Although the study of environmental adversity promises to provide important clues about individual variation in the etiology of complex psychiatric disorders, conclusive pathways to brain endophenotypes of social and antisocial behavior are largely missing. A combination of research of the long-term effects of early environmental adversity with neuroimaging may provide a powerful strategy. In the proposed project, we aim to study the impact of environmental adversities during early development on neural networks implicated in social behavior, as assessed by structural MRI and functional MRI. 280 young adults (both healthy and with current psychopathology) from an epidemiological cohort study followed since birth will be assessed. In detail, neural circuitries will be examined encompassing different dimensions of social behavior, such as social interaction, social cognition, modulation of social behavior and motivation. Candidate environmental conditions with sizeable and established effects on brain function and structure in this sample, covering prenatal and early postnatal adversities, will be investigated. The identification of neural mechanisms underlying the effects of early adversity on neural networks implicated in social behavior, and their stability over time, will help to establish more effective ways of diagnosing, preventing and treating mental disorders, especially those involved in antisocial behavior.
Holz N. Universität Heidelberg Olympia Morata-Programm: Entering the antisocial mind - development, neurobiology and new therapeutic approaches. 03/2018-02/2020.
Individuals with antisocial behavior (AB) show aggressive, deceptive, rule-violating, and destructive behaviors. AB is a hallmark feature of disruptive disorders, such as oppositional defiant disorder (ODD) and conduct disorder (CD). Since AB is only moderately heritable, the environment is suggested to play an important role in the etiology of AB, possibly affecting neural networks that trigger aggressive behavior. In terms of treatment, only limited efficacy has been reported, possibly attributable to the presence of distinct (e.g. arousal- specific) subgroups within AB, which are not yet very well characterized and would need more individualized treatments.
In the first project, the impact of early adversities and positive environments on neural networks implicated in social behavior will be investigated in 280 young adults from an epidemiological cohort study followed since birth. In detail, risk and protective factors, focusing on psychosocial and socioeconomic environments, personality factors, hormone levels, and genetic make-up that favor aggression and AB will be investigated. Using different fMRI paradigms involved in motivation, social cognition, social interactions and their modulation, the neurobiology involved in aggressive behavior will be characterized and how that is changed as a function of adverse environments. In addition, real-time smartphone-based assessments of social interactions and mood will further elucidate how daily-life social encounters may present risk or resilience factors for the development of AB.
In a second, already ongoing EU project, neural activity during reward-based decision making and emotion processing is investigated in 180 CD patients versus 90 controls. To shed light on the neural markers that differentiate between different CD groups, subtype-specific analyses based on the presence of callous-unemotional (CU) traits will be conducted. To extend the findings from project 1 to a clinically severe group of CD patients, it will be disentangled how environmental adversity may have affected these circuits and how this aberrant functioning contributes to the emergence of aggressive behavior. Moreover, specific arousal patterns have been shown to distinguish CD patients with and without CU traits, which paves the way for an individualized treatment. Through innovative, individualized biofeedback training protocols, young patients are learning how to self-regulate their arousal level (up- or downwards), depending on their “aggressotype”. This personalized, deficit-specific biofeedback training for both CD patients is currently evaluated in a controlled multicenter trial.
In sum, the results of this habilitation may help to establish more effective ways of diagnosing, preventing and treating individuals with AB.
Banaschewski T, Brandeis D. EU - Europäische Union HEALTH-F2-2013-602805: Aggressotype - WP8 Biofeedback treatment of arousal in impulsive and instrumental aggression . 11/2013-10/2018.
WP8 Biofeedback treatment of arousal in impulsive and instrumental aggression
WP8’s goal is to tackle the limitations of current behavioural and pharmacological treatments of paediatric aggression, since there is a need for innovative personalised treatment targeting the core brain and autonomous functions, such as arousal dysregulation in paediatric aggression implicated in aggression. WP8 will therefore establish the most consistent markers of distinguishing between instrumental and impulsive aggression, develop an innovative biofeedback training protocol for patients to learn self regulation of their individual specific physiological deficits in various naturalistic situations, and it will finally evaluate the effects of such personalized, deficit -specific biofeedback training for both forms of aggression in a controlled multicenter trial.