Funded Projects
Funded Projects
Website:https://imagen-europe.com/
Mental disorders are a major health problem with a lifetime prevalence of more than 25% (WHO report 2001). According to the WHO, 25% of the general population will have one or more mental disorders during their lifetime: this is a major health problem. In Europe, 34 million people in 2004 had addiction, affective, and anxiety disorders, costing society 204 billion Euros.
The use of brain imaging methods, such as Magnetic Resonance Imaging (MRI), makes it possible to understand brain mechanisms that underlie personality traits and disorders. Furthermore, we can link them to genetic variation and behavioural changes that are characteristic of disease processes.
Recent advances in genomics (the study of genes and their functions) provide new opportunities to identify genes that influence these processes, and to examine their interaction with environmental factors.
One of the major challenges addressed in this project is to assemble key biological resources and brain imaging data from human volunteers as well as animal models to understand what underlies individual behavioural differences.
The goals of assembling and investigating these materials can be achieved only through a large, inter-disciplinary collaboration that integrates groups specialised in brain imaging, human genetics and behaviour.
Why study adolescents?
75% of mental disorders appear before the age of 25. We know significant brain development takes place during adolescence. Developmental processes during adolescence are crucial for the establishment of behaviours including sensitivity to reward and punishment, impulsivity and emotional responses. These behaviours are important elements in mental disorders. Because this is such an important developmental period, factors including drug-use and stress may result in an increased risk of mental illness. The IMAGEN project aims to understand the consequences of stressors on the brain and behaviour in order to better predict the risk of mental illness and to improve treatment.
Objective 1: Identifying abnormalities in behaviours implicated in frequent psychiatric disorders
In order to understand the basis of neuropsychiatric disorders it is vital we move from simple disease classifications to ‘intermediate phenotypes’ – that is, measurable markers at the behavioural, psychological, and biological levels that may precede clinical diagnoses. Of particular relevance are individual differences in psychological traits that are implicated in frequent psychiatric disorders such as addiction disorders, anxiety disorders, hyperactivity disorders, schizophrenia, autism spectrum disorders, and personality disorders. The relevant psychological traits under study in IMAGEN are sensitivity to reward/punishment, impulsivity, and emotional response.
Objective 2: Longitudinal study design to determine the predictive value of psychological or biological traits
Because many frequent psychiatric disorders have their onset in early adulthood, it suggests that differences in psychological and/or biological processes during adolescence may have a causal or modulatory role in the development of these disorders. It is notable that adolescence is a unique and vulnerable period whereby much behavioural and brain maturation change takes place. Longitudinal studies like IMAGEN that follow adolescents over time (assessments at ages 14, 16, 19 and 22) are necessary to infer causality of these psychological and biological traits before the presentation of clinical symptoms.
Objective 3: Genetic studies to understand sensitivity to reward/punishment, impulsivity, and emotional responses.
Recent advances in technology allow the simultaneous analyses of nearly one million genes (genome-wide analysis). In addition to this approach, technology enables the identification of naturally occurring genetic variations called single nucleotide polymorphisms (SNPs), variations in the on/off switching of genes (epigenetics), and variations in the functional product of a gene (gene expression). The large number of participants in the IMAGEN study will allow researchers to relate these genetic variations to psychological traits known to be related to mental illness, such as sensitivity to reward/punishment, impulsivity, and emotional responses.
Objective 4: Brain imaging analyses to understand mental illness-related psychological traits
The adolescent participants undergo brain imaging at baseline and follow-up to study brain structure as well as the activity of the brain during various tasks. Researchers can measure individual differences in brain structure and activity, which can then be related to cognition as well as behaviours linked to frequent psychiatric disorders (i.e., responses to reward and punishment, risk-taking, impulsivity, novelty-seeking and emotional responses). Such analyses will be informative as to how the structure and activity of particular brain regions (at one time point and across time points) underlie these behaviours and, importantly, psychiatric disorders.
Objective 5: Genetic analyses of brain activity and structure
Recent research suggests that observed differences in brain activity and structure may be attributable to inter-individual differences in genetics (e.g., SNPs and epigenetics). Results from brain imaging analyses will be assessed for their association with such genetic data. Particular emphasis will be placed on genome-wide analyses as opposed to candidate gene approaches. Results obtained will be validated in other youth studies that have structural and functional MRI data.
Objective 6: How the environment shapes adolescent brain development and psychological traits linked to mental illness
An individual’s behaviour and their brain’s structure/activity are not solely determined by genetics but also by their environment and experience. Participants in the IMAGEN study are extensively characterized in terms of their experiences at school and home, their interactions with parents, friends, and peers, as well as their substance use. This wealth of data will help IMAGEN researchers understand how life’s events influence brain development and how genetics interact with the environment to modulate brain and behavioural development.
Projekthomepage: https://www.sfb1158.de/
SFB 1158: From nociception to chronic pain: Structure-function properties of neural pathways and their reorganization
What underlies the ‘Dr. Jekyll and Mr. Hyde’ nature of this key physiological function that has protected the animal kingdom from harm throughout evolution?
Why does pain convert into a disorder by becoming chronic?
And importantly, can we prevent, treat or revert these changes?
These questions are at the heart of the new Heidelberg Pain Consortium. Established by the German Research Foundation at Heidelberg University in July 2015, this centre comprises nineteen multidisciplinary projects and several associated research endeavours that span diverse, top-class clinical and basic research institutes in the twin cities of Heidelberg and Mannheim.
A key task is to understand structure-function relations that determine sensory, emotional and cognitive processes and how these functionally integrate to form a system which underlies the highly subjective experience of acute pain. A further task is to study these in the context of chronic pain, which may involve more complex networks, comprising more ‘nodes’ and a higher degree of associations, given especially, potential, complex interactions with pathways governing emotional, motivational and cognitive processes that are also involved in psychopathological disorders, such as depression, addiction and anxiety.
To tackle these goals, a highly trans-disciplinary configuration, merging expertise in classical pain research with knowledge on other pathways, disorders and methodologies, is required. Indeed, this matches the conceptual as well as the technological repertoire of scientists working together in Heidelberg and Mannheim.
Research Area A consists of projects addressing key questions on the structure, function and specificity of distinct parts of the sensory afferent-spinal cord circuitry and the identification of genetic and epigenetic mechanisms which mediate specificity as well as structural and functional plasticity.
Title: Comorbidity of chronic pain and mood disorders: breaking the vicious cycle (HaPpY)
PIs: Frauke Nees
Team: Ginevra Sperandio
The European Union has approved funding for an Innovative Training Network (ITN) as part of the MARIE SKLODOWSKA-CURIE ACTIONS. In it, scientists are looking at the mutual influence of affective disorders and chronic pain.
Until now, affective disorders and chronic pain disorders have largely been considered and usually treated separately in medicine. However, the fact that they do overlap and influence each other has become a central feature in the clinical context. These so-called comorbidities allow a poorer prognosis and increase the likelihood of complications. This can complicate the course of therapy, and the procedures used are inefficient in many cases. Which mechanisms are central in this context therefore needs to be further investigated and is a question of current research.
The focus is on the training and networking of doctoral students, who will conduct research on various aspects of the initial research question.
Participating institutions: Christian-Albrechts-Universität zu Kiel (CAU) and Schleswig-Holstein University Hospital (UKSH). Central Institute of Mental Health Mannheim, University of Heidelberg, National University of Ireland Galway, Universidad de Cádiz, Helsingin yliopisto, Heidelberg University Hospital, Universidade do Minho and partner organizations such as Université de Strasbourg, Université de Versailles-Saint Quentin-en-Yvelines, Neurofit SAS, Neurex Alsace and the European Pain Federation.
Title: The role of pandemic and individual vulnerability in longitudinal cohorts across the life span: refined models of neurosociobehavioral pathways into substance (ab)use? (CoviDrug)
Individual decisions for risky behavior, such as substance consumption, are influenced by neurobehavioral microstates, including impulsivity or maladaptive stress reactivity. These decisions have, yet, also been attributed to socio-affective cues - from macrosocial norms and opportunities, including access routes or private space, to mesosocial factors, including closeness to consuming peers or amount of familial stress. The COVID-19 pandemic provoked many restrictions and changes in social functioning along differently equipped individuals in every age cohort, and we might need to refine previously identified normative and nonnormative risk-taking trajectories for substance use prediction. Capitalizing on existing longitudinal cohort studies (IMAGEN, ROLS, MARS) and cross-sectionally fitted high-resolution real-life momentary data (IMAC-Mind), where COVID-19-related health/sociobehavioral assessments have been added during the lockdown, we will perform multivariate analyses estimating the stability of measures under COVID-19 and relations over time. We will assess new brain and daily, sensor-based behavioral data in the samples to capture risktaking/perceptions, longitudinally after-lockdown, and key features of affect regulation (mindfulness) and cross-validate age data. Factors established as protective classifiers might weaken or strengthen and new key associations of mechanisms might exhibit, including even stronger gender differences. We may gain valuable insight into pandemic health consequences in sensible periods along the life span.
Cooperation:
Prof. Dr. Dr. h.c. Dr. h.c. Herta Flor, Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Mannheim
Prof. Dr. Dr. Tobias Banaschewski, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim
Dr. Emanuel Schwarz, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim
PD Dr. Olaf Reis, Department of Psychiatry, Neurology, Psychosomatics and Psychotherapy in Childhood and Adolescence, University Medical Center Rostock
UKSH Förderstifung
Neurofeedback bei chronischen Rückenschmerzen und Möglichkeiten eines Alltagstransfers
Titel: Reducing the impact of major environmental challenges on mental health
Principal Investigator WP3 and WP8 : Frauke Nees
Team: Sebastian Siehl
Collaboration:
Prof. Dr. Gunter Schumann (Charité Berlin, Deutschland) – head of the consortium; Freie Universität Berlin (FUB); Zentralinstitut für Seelische Gesundheit (CIMH); University of Olo (UiO); Oslo Universitetssykehus Hf (OUS); Universität Potsdam (UP); RadboudUMC (RUMC); Institute for Science and Technology Austria (ISTA); University of Barcelona (UB); Universitätsklinikum Bonn (UBO); Life and Brain GmbH (LB); Ksilink (KL); Aix-Marseille Universite (AMU); Virtual Bodyworks (VB); ARTTIC Innovation GmbH (AI); Universität Jena (FSU)
Associated Partners:
Fudan University Shanghai, ISTBI (FUDAN); Georgia State University; TReNDs Center (GSU); University of Southern California (USC); Goodle Inc. (Google); King’College London (KCL); De Montfort University (DMU)
Funding: Horizon Europe (European Commission)
Abstract:
The environMENTAL project will investigate how some of the greatest global environmental challenges, climate change, urbanisation, and psychosocial stress caused by the COVID-19-pandemic affect mental health over the lifespan. It will identify their underlying molecular mechanisms and develop preventions and early interventions. Leveraging cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large scale behavioural neuroimaging cohorts, we will identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress and substance abuse. By linking population and patient data via geo-location to spatiotemporal environmental data derived from remote sensing satellites, climate models, regional-socioeconomic data and digital health applications, our interdisciplinary team will develop a neurocognitive model of multimodal environmental signatures related to transdiagnostic symptom groups that are characterised by shared brain mechanisms. We will uncover the molecular basis underlying these mechanisms using multi-modal -omics analyses, brain organoids and virtual brain simulations, thus providing an integrated perspective for each individual across the lifespan and spectrum of functioning. The insight gained will be applied to developing risk biomarkers and stratification markers. We will then screen for pharmacological compounds targeting the molecular mechanisms discovered. We will also reduce symptom development and progression using virtual reality interventions based on the adverse environmental features - developed in close collaboration with stakeholders. Overall, this project will lead to objective biomarkers and evidence-based pharmacologic and VR-based interventions that will significantly prevent and improve outcomes of environmentally-related mental illnesses, and empower EU citizens to manage better their mental health and well-being.
WP3: Development and implementation of digital health assessments
WP8: Digital intervention (Development of a virtual reality programme using reinforcement learning)
Website: https://compain.weebly.com
Title: The Complexity of Pain and Its Normative Implications
Pain has long been characterized as a subjective experience: something inherently personal, private, and unknowable by others. At the same time, however, there have been repeated attempts to understand this subjective experience better by objective means. The neurosciences are researching the nerve processes with regard to pain in ever more detail and agree in their results with neurophilosophy that pain must be understood as a complex phenomenon, likely comprised of different building blocks. These building blocks are also influenced and shaped by other cognitive processes, such as memory of past pains or imagination of possible pains. The term “pain” then likely refers not to a single phenomenon, but rather a family of different phenomena. This insight has not played much of a role in discussions of pain in (bio)ethics, however. Here, pain is still predominantly treated as one singular phenomenon that is generally characterized in a normative way by the fact that it is unpleasant and should be avoided or alleviated. Based on this highlighted difference between the view of pain as complex in neuroscience and theoretical philosophy, and a more simple or unified view of pain in ethics, the primary research goal of the COMPAIN consortium is to bridge this gap. We investigate to what extent the new view of pain in the neurosciences and in philosophy must influence the normative evaluation of pain in (practical) ethics. To achieve this, the research consortium firstly examines existing categorisations of pain in neuroscience and philosophy and identifies ethically relevant criteria for their evaluation; building on this work, in a second step, we develop a new systematic proposal of pain across scientific disciplines, which we will validate through cross-cultural surveys; and thirdly, we normatively evaluate this systematization proposal and develop recommendations for their implementation in clinical practice.