Startle potentiation to unpredictable threat and the internalizing spectrum.

An increased sensitivity to ambiguity, uncertainty, and unpredictability has been implicated in multiple psychiatric disorders. Research has indicated heightened startle potentiation, a psychophysiological indicator of defensive motivation, to unpredictable threat in panic disorder, posttraumatic stress disorder, social anxiety disorder, and specific phobia, and mixed relationships with depression and generalized anxiety disorder. The present study examined whether heightened startle potentiation to unpredictable threat was associated with the higher-order internalizing spectrum. The sample included 193 18-35-year-olds (86% assigned sex female) oversampled for psychiatric disorders. Participants completed the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-Research Version to assess lifetime history of psychiatric disorders and the no, predictable, and unpredictable threat task to measure startle potentiation to predictable and unpredictable threat. Results indicated heightened startle potentiation to unpredictable, but not predictable, threat in participants with a lifetime history of a major depressive episode, generalized anxiety disorder, posttraumatic stress disorder, specific phobia, obsessive-compulsive disorder, and eating disorder. Higher-order mediational modeling indicated greater startle potentiation to unpredictable threat was associated with higher scores on a latent internalizing dimension, which accounted for all associations between startle potentiation to unpredictable threat and individual disorders. No externalizing disorder or latent externalizing dimension was associated with startle potentiation to predictable or unpredictable threat. The present study suggests that heightened startle potentiation to unpredictable threat relates to the internalizing spectrum. The study also highlights how higher-order dimensions can advance understanding of the core mechanisms of psychiatric disorders. (PsycInfo Database Record (c) 2026 APA, all rights reserved).