Neural Mechanisms of Human Safety Learning - Towards New Treatment Strategies for Anxiety Disorders

• Applicant: Professor Dr. Raffael Kalisch
• Subject Area: Biological Psychiatry
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 32909890

Anxiety disorders place a great burden on patients and on society. Current treatments are still unsatisfactory. The objective of this project is to generate new therapeutic approaches by advancing our understanding of the neurobiological mechanisms of safety learning. Safety learning describes a process by which an individual learns that a feared stimulus is not as threatening as expected, resulting in an attenuation of anxiety responses. In psychotherapy, safety learning is promoted through extinction training and voluntary reappraisal. To study the role of the glutamatergic and dopaminergic neurotransmitter systems in these safety learning processes, healthy normal volunteers will either extinguish or reappraise conditioned anxiety responses during a pharmacological manipulation selectively stimulating or inhibiting a given neurotransmitter system. In a complementary approach, the effects of norm variants in genes determining the activity of these neurotransmitter systems on the above learning processes will also be studied. Concurrent functional magnetic resonance imaging (fMRI) will enable us to identify the neural networks involved and to study where in the brain a given neurotransmitter exerts its actions on safety learning. The knowledge generated by this project will be used to design future clinical studies in anxiety patients aiming to determine whether and how extinction or reappraisal performance during psychotherapy can be enhanced pharmacologically (thus improving treatment response) and predicted genetically (thus allowing for individual tailoring of treatment decisions).

• DFG Programme: Independent Junior Research Groups