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Nat Protoc. 2012 Feb 23;7(3):527-32. doi: 10.1038/nprot.2012.001.

Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test).

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Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, Maryland, USA.


The threat of predictable and unpredictable aversive events was developed to assess short-duration (fear) and long-duration (anxiety) aversive states in humans. A typical experiment consists of three conditions: a safe condition (neutral (N)), during which participants are safe from aversive stimuli, and two threat conditions-one in which aversive events are administered predictably (P) (i.e., signaled by a threat cue), and one in which aversive stimuli are administered unpredictably (U). During the so-called NPU-threat test, ongoing change in aversive states is measured with the startle reflex. The NPU-threat test has been validated in pharmacological and clinical studies and can be implemented in children and adults. Similar procedures have been applied in animal models, making the NPU-threat test an ideal tool for translational research. The procedure is relatively short (35 min), simple to implement and generates consistent results with large effect sizes.

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