Event-related potentials to acoustic startle probes during unpredictable threat are associated with individual differences in intolerance of uncertainty

Individual differences in sensitivity to unpredictable threat may be a critical mechanism for internalizing psychopathology phenotypes. The present study examined whether the startle probe-elicited N100 and P300 during unpredictable threat - two event-related potentials indexing early and elaborative attentional processing of unpredictable threat - may be endophenotypes for internalizing psychopathology, including fear and distress/misery disorders and intolerance of uncertainty (IU), a clinical trait that is transdiagnostically associated with internalizing disorders. A large sample of adult siblings (N = 375) completed the no, predictable, and unpredictable threat task, during which the N100 and P300 were recorded. Relative to the no threat condition, N100 was more strongly enhanced in anticipation of unpredictable than predictable threat while P300 was suppressed to both predictable and unpredictable threat. While neither N100 enhancement nor P300 suppression to unpredictable threat was associated with fear or distress/misery disorders, they were negatively linked to inhibitory IU (a facet of IU). Thus, individuals high in inhibitory IU showed reduced attentional engagement with the threatening context when it was unpredictable. Further, N100 enhancement and, to a lesser degree, P300 suppression to unpredictable threat showed familial aggregation - a key criterion for determining whether a biomarker is an endophenotype. In sum, N100 enhancement and P300 suppression to unpredictable threat may be endophenotypes for dimensional measures of internalizing psychopathology.