An intolerance of uncertainty (IU) and increased sensitivity to unpredictability has been identified as a potential transdiagnostic mechanism of psychopathology. We are conducting a series of studies on the impact of the (un)predictability of threat on anticipatory defensive motivation and attention. To test this in the laboratory, we use a variant of the no, predictable, and unpredictable threat (NPU-threat) task, which contains three within-subject conditions: 1) no threat (N; participants are safe from threat), 2) predictable threat (P; threat is signaled by a short duration cue), and 3) unpredictable threat (U; threat is unsignaled). The startle eye blink and ERPs are measured as psychophysiological indicators of defensive motivation and attention. In one set of studies, we are examining the relationship between sensitivity to unpredictable threat, anxiety and depression symptoms, and risk for psychopathology in adolescents. In a separate set of studies, we are examining the impact of threat predictability and the type of threat stimulus on the startle eye blink, ERPs, and salivary biomarkers of inflammation.