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.
Brandeis D. EU - Europäische Union 684809: NEWROFEED - für Kinder und Jugendlichen mit einer AD(H)S. 09/2016-10/2017.
Die Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) ist eine der häufigsten psychischen Erkrankungen bei Kindern und Jugendlichen. Obwohl es gute Möglichkeiten der psychotherapeutischen und medikamentösen Behandlung gibt, besteht eine große Nachfrage nach alternativen und ergänzenden Therapiemethoden. Neurofeedback ist ein neueres nichtmedikamentöses therapeutisches Verfahren, bei dem Patienten lernen können, die elektrische Aktivität ihres Gehirns gezielt zu regulieren. Die NEWROFEED-Studie untersucht erstmals die Wirksamkeit eines personalisierten Neurofeedback-Trainingsgeräts für den Heimgebrauch (ADHD@Home) im Vergleich mit medikamentöser Therapie bei der Behandlung von Kindern und Jugendlichen mit ADHS (7–13 Jahre). Nach einer ausführlichen Diagnostik werden die Teilnehmer nach dem Zufallsprinzip in einem Verhältnis von 3:2 einer Neurofeedback-Behandlung oder einer medikamentösen Behandlung mit dem Wirkstoff Methylphenidat zugeteilt. Die Teilnehmer der Medikamenten-Gruppe erhalten eine individuelle medikamentöse Einstellung und Behandlung durch einen erfahrenen Kinder-und Jugendpsychiater. Die Teilnehmer der Neurofeedback-Gruppe und deren Eltern werden ausführlich in die Nutzung des Neurofeedback-Trainingsgerätes eingewiesen und führen anschließend das Neurofeedback-Training zuhause auf einem Tablet-Computer durch. Das Training umfasst 40 Sitzungen von jeweils 45 Minuten. Dabei wird die Hirnaktivität im Rahmen kleiner Spiele in Echtzeit zurückgemeldet. Die Dauer der Studienteilnahme beträgt insgesamt circa 3 Monate. Ziel der Studie ist nachzuweisen, dass das personalisierte Neurofeedbacktraining einer sorgfältigen medikamentösen Behandlung in der Wirksamkeit nicht unterlegen ist.
Dittmann RW. EU - Europäische Union 278948: TACTICS: Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes. 01/2012-12/2016.
Compulsivity is characterized by a repetitive, irresistible urge to perform a behavior, the experience of loss of voluntary control over this intense urge, the diminished ability to delay or inhibit thoughts or behaviors, and the tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is a cross-disorder trait underlying phenotypically distinct psychiatric disorders that emerge in childhood (autism spectrum disorder, ASD; obsessive-compulsive disorder, OCD) or adolescence (substance abuse). Our approach integrates clinical data sets for ‘addictive’ (ADHD high risk for substance use), ‘anxious’ (OCD) and ‘stereotypical’ (ASD) compulsive behaviors with highly predictive animal models for new pharmacotherapy. In a series of ‘proof-of-concept’ studies, the cohesion of structural neuroimaging studies (MRI/DTI), neurochemistry (MRS/microdialysis), behavior, genetics (GWAS), proteomics and (Bayesian) machine learning tools in both male and female paediatric clinical populations and behavioral animal models will seek to better understand underlying mechanisms related to glutamate dysfunction in frontostriatal circuits and its remediation / prevention by early intervention studies with glutamate-based (riluzole and memantine) clinically used drugs. The leading drug-based interventions will be tested in pilot Phase IIb-like studies for ‘proof-of-principle’ efficacy in paediatric OCD and ASD populations. This approach will 1) establish predictive neural, genetic and molecular markers of compulsivity in pediatric populations; 2) provide evidence of disorder modifying pharmacologic strategies as a therapeutic approach; 3) develop a novel animal model for pharmaceutical screening and proof of concept studies, 4) build and valorize a translational biomarker compulsivity database and 5) provide pilot efficacy and safety data in paediatric clinical populations to support future large scale clinical trials according to these strategies.