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Fear learning and extinction

Experimental fear conditioning and extinction represent basic forms of associative learning with considerable clinical relevance and serve as laboratory models for the development and treatment of anxiety disorders, respectively. There is considerable inter-individual variation in the ability to acquire and extinguish conditioned fear reactions as well as the return of fear and approximately one third of the variance in human fear conditioning and in the vulnerability for anxiety disorders can be attributed to genetic factors. The experimental paradigms of fear conditioning and extinction are particularly well suited for genetic association studies as these optimally investigate simple behavioral paradigms with sufficient inter-individual variability and clear heritability that elicit robust behavioral responses which are easy to measure and quantify and rely on a well-defined underlying neural circuitry. Understanding the molecular pathways that mediate conditioning and extinction might therefore make an important contribution to the study of anxiety pathophysiology and resilience. Because a significant proportion of patients do not respond to or tolerate standard treatments, such advances may ultimately open up new perspectives for pharmacological interventions (i.e. pharmacologically enhanced CBT) or the individualization of current prevention and treatment programs. In the future, translational work employing a synergy between molecular genetics, neuroimaging, psychophysiology and psychopharmacology will be powerful in unraveling the neurobiology of fear learning and extinction processes and the investigation of genetic polymorphisms in fear learning and extinction processes represents one avenue along this path.