Forschung
Was passiert im Gehirn, wenn wir Angst erleben? Wie verändert Psychotherapie das Gehirn? Können wir durch ein besseres Verständnis der Mechanismen auf Ebene des Gehirns unsere psychotherapeutischen Techniken optimieren?
Diesen und anderen spannenden Fragen widmen wir uns in unserer Forschung. Unser Ansatz folgt einer bio-behavioralen, grundlagenorientierten Perspektive. Wir verwenden experimentelle Paradigmen, die ein hohes translationales Potential für die Psychotherapieforschung aufweisen, z.B. zum emotional-assoziativen Lernen. Unser Methodenspektrum umfasst bildgebende Verfahren (Magnetresonanztomographie), die wir in einem multimodalen Ansatz mit peripher-physiologischen (Herzrate, Respiration, Hautleitfähigkeit), neuroendokrinen (Speichelcortisol) und (epi)genetischen Daten kombinieren. Wir setzen multivariate Methoden der Mustererkennung im Rahmen des maschinellen Lernens ein, um prädiktive Marker für den individuellen Patienten zu generieren. Unser Schwerpunkt liegt dabei auf einem besseren Verständnis der biopsychologischen und neurowissenschaftlichen Grundlagen normaler und pathologischer Formen von Angst und deren Behandlung mittels expositionsbasierter kognitiver Verhaltenstherapie (KVT).
Laufende Forschungsprojekte:
Title: Dynamic belief updating in the anxiety phenotype: developmental aspects and salience context (Research Unit)
Funding: DFG FOR5646 (Principle Investigator)
Duration: 2024-2028
Collaborators: Universität Hamburg, Humboldt-Universität zu Berlin, Freie Universität Berlin, Friedrich-Schiller Universität Jena
Abstract:
Background: Learning is key to survival when facing dynamically changing environmental threats. Many environments are characterized by uncertainty due to (1) irreducible outcome variability, e.g., when the location of an attacking predator can only approximately be predicted, and (2) uncertainty arising from systematic changes, e.g., when the location in which a predator appears, changes systematically. An adequate consideration of these types of uncertainty requires dynamic belief updating (DynBU), promoting survival by balancing explorative vs. defensive behaviors. This pertains particularly to internal models of threats. Aims: We provide an in-depth behavioral and neural analysis of statistical learning, particularly DynBU, as a function of the anxiety phenotype across the lifespan. Further, the project examines if individual ifferences in DynBU in anxiety disorder (AD) patients can be related to intervention-driven changes (cognitive behavioral therapy) in threat expectations. Hypotheses: (1) We hypothesize an overestimation of how much should be learned from new outcomes (learning rate) in the anxiety phenotype, shaped by defensive reactions. This effect will particularly be dependent on the presence of expected uncertainty. We further assume a correlation between anxiety and learning-rate related activity in the prefrontal and parietal cortex as well as a stronger involvement of the periaqueductal gray (PAG) in higher anxiety levels. (2) We hypothesize a negative correlation between age and the tendency to show overly high learning rates under expected uncertainty, as well as a moderation of this effect by the anxiety phenotype. On an exploratory level, (3) we will test the applicability of clinical and experimental paradigms in a younger group of children (aged 8 to 9 years), and (4) target the relation between DynBU and threat expectations during exposure treatment. Planned methods: Participants will report on relevant clinical information (see clinical backbone). They will further complete the common Confetti-Cannon-Task (comparison across all projects) and a salience context sensitive Predator-Task (comparison with project 5). Finally, an adult subsample will complete the Predator-Task in the MRI scanner which will offer important insights into the neural systems of statistical learning under heightened defensive reactivity in the anxiety phenotype. Expected impact: The current project will enrich the RU's goals, mainly aim 2 (developmental and environmental context influences) and aim 3 (clinical manifestations of DynBU). We will extend the RU's clinical focus by including the anxiety phenotype from childhood to adulthood. A shared paradigm allows comparability across development (projects 6 & 7) and psychopathology (projects 2 & 9). This will allow for developing and testing innovative treatments focusing on uncertainty processing for the prevention and early intervention of AD during a putative second funding period.
Title: German Center for Mental Health / Deutsches Zentrum für Psychische Gesundheit (DZPG)
Funding: BMBF (Principle Investigator)
Duration: 2023-2025, structural funding pending
Participating Sites: Berlin-Potsdam, Bochum-Marburg, Halle-Jena-Magdeburg, Mannheim-Heidelberg-Ulm, Munich-Augsburg, Tübingen
Collaborators Site Berlin/Potsdam: Charité – Universitätsmedizin Berlin, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke, Freie Universität Berlin, Max-Delbrück-Centrum für Molekulare Medizin, Max Planck UCL Center for Computational Psychiatry Berlin/London, Robert Koch-Institut, Universität Potsdam, Universitätsklinikum Freiburg
Abstract:
The perception of the serious individual and societal consequences of mental illness is the basis for the German Center for Mental Health (DZPG). These consist of the enormous burden on 17.8 million patients and their families in Germany per year, low access to treatment for those affected and, as a consequence, increased mortality and annual costs of €44 billion caused by untreated or inadequately treated individuals. Therefore, with the DZPG, the BMBF has established another health center, which, with its focus on translational health research, ensures that innovative therapeutic approaches are generated and enter the care system in a timely manner to close the development of new, effective prevention, diagnosis and treatment methods for mental illnesses. In addition, the DZPG is expected to find solutions to the unacceptable societal inequities in the care of people with mental illness. These exist both in the "horizontal perspective," such as between rural and urban living environments, and in "vertical contexts," such as with regard to vulnerable groups (e.g., people without jobs or people with a migration background, who are particularly affected by mental illness and find it more difficult to access care services).
The DZPG is establishing an ambitious translational research program that aims to focus on promoting mental health and resilience, increase awareness of mental illness, and reduce the burden of mental illness across all age groups over the next 15 years. The main partners in the DZPG are the six sites and the representatives of the Center Council (an association of affected individuals and their families in the Patient and Public Involvement (PPI) infrastructure). The research program is structured around three research domains (Domain I: Risk factors in early development, especially trauma and early stressors; Domain II: Investigation and improvement of psychosocial, psychotherapeutic, pharmacological and neuromodulatory interventions and their combination in transdiagnostic patient groups; Domain III: Prevention, participation and recovery in relevant living environments). Based on these thematic priorities, the DZPG has developed three Flagship (FL) projects (Flagship I (FLI): risk factors and prevention programs for mental illness in an urban setting; Flagship II (FLII) network of early intervention centers; Flagship III (FLIII): Stepped Care Approaches for low-threshold support services to vulnerable populations).
Title: Towards precision psychotherapy for non-respondent patients: from signatures to predictions to clinical utility (Research Unit)
Funding: DFG FOR5187 (Spokesperson)
Duration: 2022-2026
Collaborators: Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité – Universitätsmedizin Berlin, Psychologische Hochschule Berlin
Abstract:
Although cognitive-behavioral therapy (CBT) is a first-line treatment for internalizing disorders, a substantial proportion of patients fails to benefit - with severe consequences for patients and costs for societies. Precision mental health can help to identify patients at risk for non-response (NR) already prior to treatment initialization. The paucity of standard clinical features that allow for single-case predictions serves as an impetus to search for additional layers of NR. The work program of this Research Unit (RU) will foster the development of precision psycho-therapy by i) investigating clinical and bio-behavioral signatures of NR to improve our under-standing of this phenomenon, ii) applying state-of-the-art machine learning technology for single-case predictions, and iii) validating these for clinical utility in an ecologically valid treatment setting, bringing together four major academic outpatient clinics in Berlin. Our effort will thus pave the way for a priori patient stratification to intensified or augmented treatments in a putative second funding period. To achieve this, we will set up a prospective-longitudinal multi-center observational study on n = 500 patients with internalizing disorders (specific phobia, social anxiety disorder, panic disorder, agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, unipolar depressive disorders) who will be deeply phenotyped prior to CBT using hypotheses-based clinical, e-mental health, psychophysiological and neuroimaging measures. Assessment batteries and treatment documentation will be harmonized across centers. Predictive analytics will be provided by our methods platform, including computer vision algorithms such as convolutional neural networks, multiple kernel and transfer learning and an infrastructural basis (hard- and software, data management plans, high-performance computing). The RU aims to significantly improve the field by 1) setting up a multi-level and -method assessment battery to search for the best predictors, combinations thereof, and cost-efficient proxies, 2) investigating bio-behavioral signatures of emotion regulation as a putative key mechanism of CBT, 3) applying a transdiagnostic focus on NR signatures, 4) within one comprehensive sample that exerts a high degree of ecological validity, thus fostering translation to clinical practice with diverse patient characteristics. These goals can only be achieved by concerted action of experts in the fields of clinical psychology, psychothera-py, e-mental health, psychophysiology, cognitive neuroscience, and neuroinformatics. We will maximize synergies with large-scale consortia (UK Biobank, ENIGMA, CRC-TRR 58, BMBF psychotherapy initiative, PING, KODAP). This RU will make substantial progress in answering the question how we can better understand the phenomenon of NR, identify and address this vulnerable and cost-intensive group of NR patients.
Title: Stressfrei nach Corona: ein psychologisches Hilfsprogramm
Duration: 2020-2022
Abstract:
Psychological distress in the aftermath of the Covid-19 pandemic may be caused by many sources such as threat to physical health (i.e. the virus itself), restricted social interactions, restricted civil rights, long crisis duration and high economic uncertainty. Evidence from other traumatic and catastrophic events suggest that the “incubation time” of psychological problems and symptoms caused by the current crisis will expand to the post-pandemic time, i.e. months to years following the event. Information about the nature and amount of mental problems is urgently needed to inform health care providers about the need for psychological treatments targeting the sequela of this pandemic. We aim to map the unique psychological signature of this novel event, its impact on individuals and societies from a clinical perspective and to apply a stepped-care approach with a scalable online treatment, followed by group face-to-face intervention for individuals presenting with residual symptoms.
Learn more: www.corona-stressfrei.de
Title: ENIGMA-SP: A large-scale meta-analysis on the brain’s structural alterations in specific phobia
Duration: 2018-2021
Abstract:
Specific phobia is one of the most common mental disorders and has been used as a model disorder to investigate the neural processing of fear and fear circuitry dysfunctions. Research on potential alterations in structural brain anatomy however is still scarce, although these may underlie the disorder-related functional changes and thus yield valuable insights in the neurobiology of specific phobia related pathogenic mechanisms. Additionally, comparative research on the phobia subtypes with partly different behavioral, autonomic and neural response patterns (e.g. animal vs blood-injection-injury subtype), is needed in order to provide further information about the underpinnings of their phenomenological differences and potential targets for optimizing their treatment.
Embedded within the ENIGMA initiative, this project employs a large-scale meta-analysis on the neurostructural alterations in specific phobia. It targets published but also unpublished phobia datasets from researchers worldwide. The project aims to examine common neural correlates of all phobia subtypes, investigate subtype-specific signatures, and elucidate the role of severity and comorbid depression.
ENIGMA Webpage: http://enigma.ini.usc.edu/ongoing/enigma-anxiety/
Title: Exposure treatment in anxiety disorders: proof of principle of an a priori response prediction approach
Funding: SFB-TRR 58 (Principal Investigator)
Duration: 2016-2020
Abstract:
The aim of this project (SFB-TRR 58; C09) is to a priori predict treatment outcome in anxiety disorders following behavioral exposure based on neurobiological measures with high accuracy in a second, independent sample. We will build upon findings from previous mechanistic studies of the CRC and incorporate them into the development of a predictive pattern comprising fear-relevant (epi-) genotypes, neuropsychological, phenotype and neuroimaging markers. Multivariate pattern analyses embedded within a machine learning framework will be used to generate predictions on the individual patient level and to cross-validate markers in a second sample. We expect this project to bridge the translational gap between basic and clinical research and bring stratified medicine approaches into reach as one of the long-term goals of this collaborative research center.
Webpage: https://campus.uni-muenster.de/sfbtrr58/the-project/
Title: Gene-environment interactions, neural circuits and generalization in dimensional endophenotypes of fear and anxiety in adults and children: development and reversibility
Funding: SFB-TRR 58 (Principal Investigator)
Duration: 2016-2020
Abstract:
In this core project (SFB-TRR 58; Z02) 1.500 adult healthy volunteers as well as 500 adolescent healthy volunteers, first recruited within the 2nd funding period and by now between 12 and 16 years old, will be enrolled or catamnestically evaluated, respectively. Adult and adolescent individuals will be characterized for several anxiety-relevant psychometric measures such as anxiety sensitivity as well as for life events in childhood and adulthood. These individuals will also be genotyped for genetic/epigenetic variation in candidate genes of fear and anxiety as well as on a whole-genome scale. Applying a GxE(xC) approach the complex-genetic basis of dimensional endophenotypes of fear and anxiety in adults and adolescents will be investigated regarding candidate stressors (e.g., childhood trauma, recent negative life events), resilience-increasing coping mechanisms potentially antagonizing stressors and candidate genes, extended by an epigenetic level (DNA methylation). Large-scale meta-analytic neuroimaging analyses both on a dimensional and categorical level will be carried out including multimodal approaches such as “imaging (epi)genetics”. The identification of predictive biomarkers on an (epi)genetic, psychophysiological and neuroimaging level in synopsis with life history data and intra-individual dynamics in the evolution of anxiety and fear is expected to contribute to the development of innovative therapeutic and preventive modules and their individualized application.
Webpage: https://campus.uni-muenster.de/sfbtrr58/the-project/
Title: Forschungsnetzwerk Angsterkrankungen: “Providing Tools for Effective Care and Treatment of Anxiety Disorders (AD): Outcomes, Mediators and Moderators of Enhanced Extinction Learning” (PROTECT-AD)
Funding: Bundesministerium für Bildung und Forschung (BMBF; Collaborator)
Duration: 2015-2018
Abstract:
All anxiety disorders (AD) share elevations of fear acquisition and deficits in fear extinction, both of which contribute to the persistence of excessive fear. Exposure-based therapy (ET), derived from principles of fear extinction, is the most empirically supported treatment for AD. However, most adult and child AD do not receive treatments that target effective extinction learning, although AD are early onset, prevalent, and without therapy persistent disorders associated with exceedingly high avoidable costs and lifelong clinical-developmental risks. Our established basic and clinical research network translates recent research on fear, anxiety and extinction learning into a modular enriched treatment to augment extinction learning during ET for AD. Based on two RCTs, we hypothesize that providing more exposure trials over a shorter duration (“intensified”) during active therapy and spaced trials in various contexts during follow-up will enhance extinction learning and reduce relapse, leading to stronger, faster and more pervasive outcome effects in subjective, behavioral, physiological, neural and epigenetic indices of fear. Two additional methods for enhancing extinction learning are pa-rental participation (context generalization in child AD, P2) and facilitating positive prediction error. We link the RCT to in-depth experimental paradigms targeting behavioral/psychophysiologic (P3), neural (P4) and (epi)genetic (P5) mediator mechanisms as well as moderators of outcome (i.e. P6) to identify extinction-related mechanisms of treatment. Avoiding traditional transfer barriers and involving stakeholder groups (P7), we expect to provide improved treatment procedures for developmentally targeted care of adult and child AD, and facilitate transfer to routine care.
Webpage: https://psy2.psych.tu-dresden.de/i2/klinische/Studien/protect/index2.html