TRR 58:  Fear, Anxiety, Anxiety Disorders

• Subject Area: Medicine ; Agriculture, Forestry and Veterinary Medicine ; Social and Behavioural Sciences
• Term: from 2008 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 44541416

Fear and anxiety are crucial adaptive components of the behavioural repertoire that are generated in anticipation of or in response to stimuli, which threaten to perturb homeostasis. Anxiety-related states appear to represent part of a universal survival strategy of the organism, with inter-individual variation reflecting an evolutionary principle related to the survival of the individual population. Extreme variation or perturbation of these mechanisms can lead to disproportional and prolonged (even irreversible) states, which are, for instance, experienced as excessive, persistent or generalised anxiety. This sort of maladaptive anxiety, generally, reflects an underlying pathology, an anxiety disorder, requiring treatment. These are common diseases with a lifetime prevalence of about 25 percent, imposing a major challenge to health care and economy.
The aim of the Transregional Collaborative Research Centre is to concentrate expertise in the fields of molecular biology, genetics, neurophysiology, psychology, psychiatry and neuroimaging, in order to provide a better understanding of the mechanistic basis of anxiety states and disorders.
The expertise of the participating institutions from the universities of Münster, Hamburg, Mainz and Würzburg is largely complementary and forms the basis of a two-step interdisciplinary scientific concept. In a first step, "established" candidate genes, pathways and paradigms are used, in order to ensure maximal control of experimental conditions and to construct links between animal and human studies.
The major goal is to provide mechanistic explanations of selected components of fear responsiveness, including perception, acquisition and specifically extinction of fear, with particular reference to clinical relevance. In a second step, "novel" innovative genes are identified under these controlled experimental conditions and are tested as candidate genes using the established experimental paradigms to underscore their biological relevance. As a corollary of this dual strategy and a second long-term goal, risk profiles will be sharpened based upon improved understanding of the neurobiological, genetic and environmental substrates, which in turn will pave the way for individually tailored therapy.

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Life history, serotonin transporter genotype and anxiety-like behaviour: testing the "coping-with-challenge hypothesis" (Project Heads Lesch, Klaus-Peter ;  Richter, Sophie Helene ;  Sachser, Norbert )
• A02 - Contribution of CRF and 5-HT in the antero-dorsal BNST on phasic and sustained fear in freely behaving mice (Project Head Seidenbecher, Thomas )
• A03 - Distinct circuits of the extended amygdala regulating fear generalization and extinction (Project Head Pape, Hans-Christian )
• A04 - Cell type-specificity of endocannabinoid signaling in amygdala-BNST projections regulating sustained fear (Project Heads Lutz, Beat ;  Pape, Hans-Christian )
• A05 - Stress-induced programming in serotonin (5-HT) system-modified mice: epigenetic editing as a strategy to cope with anxiety (Project Heads van den Hove, Ph.D., Daniel ;  Lesch, Klaus-Peter ;  Schmitt-Böhrer, Angelika )
• A06 - Serotonin and the behavioral neurogenetics of safety-learning in fruit flies (Project Head Gerber, Bertram )
• A08 - Impact of the Neuropeptide S system and NPS-receptor polymorphisms on fear and anxiety (Project Head Jüngling, Kay )
• A09 - The role of local reciprocal inhibitory interactions in prefrontal cortex for the central regulation of fear expression (Project Head Zhang, Weiqi )
• A10 - Role of hippocampal BDNF signaling in contextual fear learning, fear generalization and context discrimination (Project Heads Blum, Robert ;  Sendtner, Michael A. )
• B01 - Context conditioning: Generalization, discrimination, extinction, and the influence of risk factors (Project Heads Pauli, Paul ;  Wieser, Matthias J. )
• B03 - The dynamics of fear generalization (Project Head Büchel, Christian )
• B04 - Coherence as a mechanism for response selection: interaction of emotion and attention (Project Heads Büchel, Christian ;  Engel, Andreas K. )
• B05 - The role of anticipated and perceived bodily threat in fear and anxiety (Project Heads von Leupoldt, Andreas ;  Wieser, Matthias J. )
• B06 - The role of NOS-I mediated 5HT1a signalling in hippocampusdependent fear conditioning (Project Heads Büchel, Christian ;  Kalisch, Raffael ;  Reif, Andreas )
• B07 - Longitudinal and multimodal investigations of the modulation of fear- and anxiety-related processes by life adversity - predictive and buffering factors. (Project Head Lonsdorf, Tina Barbara )
• B08 - The BDNF system as mediator for stress impaired fear acquisition, extinction and late fear (Project Heads Andreatta, Marta ;  Lange, Maren Denise )
• B09 - Stress, fear generalization, and habitual responding (Project Head Schwabe, Lars )
• B10 - The influence and interaction of the dopaminergic and endocannabinoid system on extinction learning mechanisms (Project Head Haaker, Jan )
• C01 - Anxiety driven imbalance of top-down and bottom-up processing during emotion perception and affective associative learning (Project Heads Junghöfer, Markus ;  Pantev, Christo ;  Zwanzger, Peter )
• C02 - Targetable (Epi)Genetic, Physiological and Neuroimaging Risk Markers of Anxiety Sensitivity: A Developmental, Cross-Disorder Prevention Study of Separation Anxiety and Panic Disorder (Project Heads Domschke, Ph.D., Katharina ;  Neufang, Susanne )
• C04 - Function of the prefrontal cortex in patients with panic disorder: fNIRS and fMRI measurements during emotional Stroop and Attentional Blink paradigms with and without TMS intervention (Project Heads Ehlis, Ph.D., Ann-Christine ;  Fallgatter, Andreas Jochen )
• C07 - Phasic and sustained fear in humans: neural basis and implication for anxiety disorders (Project Heads Herrmann, Martin J. ;  Straube, Thomas )
• C08 - Hemodynamic (fMRI) and magnetoencephalographic (MEG) correlates of fear-generalization in anxiety disorders: developmental aspects and effects of psychotherapy (Project Heads Junghöfer, Markus ;  Straube, Thomas )
• C09 - Exposure treatment in anxiety disorders: proof of principle for an a priori response prediction approach (Project Heads Dannlowski, Udo ;  Lüken, Ulrike )
• C10 - Interaction of attentional and learning processes during acquisition, generalization and loss of fear (Project Head Gamer, Matthias )
• Z01 - Central Tasks of the Transregional Collaborative Research Centre (Project Head Pape, Hans-Christian )
• Z02 - Gene-environment interactions, neural circuits and generalization in dimensional endophenotypes of fear and anxiety in adults and children: development and reversibility (Project Heads Dannlowski, Udo ;  Deckert, Jürgen ;  Domschke, Ph.D., Katharina ;  Lonsdorf, Tina Barbara ;  Lüken, Ulrike ;  Pauli, Paul ;  Romanos, Marcel )

• Applicant Institution: Universität Münster
• Co-Applicant Institution: Julius-Maximilians-Universität Würzburg; Universität Hamburg
• Participating Institution: Johannes Gutenberg-Universität Mainz
• Spokesperson: Professor Dr. Hans-Christian Pape