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Experimental psychopathology is the application of experimental methods to the study of psychopathology and its underlying processes. The study of individual differences in the development, maintenance and/or relapse of psychopathology is currently at the forefront of research. Stressful events are known to exert a substantial impact on our lives. Why however, do some people react in an extremely adaptive way, while others develop pathology in the aftermath of a trauma? One particularly interesting individual differences factor is genetic makeup and the aim of this paper is to review the current state of the art of genetics in experimental psychopathology which is illustrated by using fear conditioning as an exemplary model in the study of mechanisms underlying anxiety. We identify and discuss current challenges of the field and provide recommendations on how these can be met. In addition, criteria for experimental models of psychopathology as well as future directions are discussed. [ABSTRACT FROM AUTHOR]

Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB(1) receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB(1) or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-)clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB(1) agonist. [ABSTRACT FROM AUTHOR]