Transdiagnostic physiological correlates of unpredictable threat anticipation

Abstract

Responses to unpredictable threat have been proposed as a candidate mechanism in anxiety-related psychopathology, but clinical findings remain heterogeneous and often rely on single physiological outcomes. The present study examined whether physiological responses during threat anticipation map onto categorical and dimensional conceptualizations of psychopathology across the anxiety and obsessive-compulsive spectrum. In a transdiagnostic sample of N = 163 participants, patients with specific phobia, social anxiety disorder (SAD), and obsessive-compulsive disorder (OCD), as well as unaffected controls completed the NPU-threat test in order to measure responses to predictable and unpredictable threat. Physiological responding was assessed using startle reflex, skin conductance responses (SCR), and event-related potentials indexing early sensory processing (N1) and later attentional allocation (P3). Results indicated a group-based effect for SCR, such that patients with OCD showed enhanced autonomic responding during unpredictable threat anticipation. Dimensionally, anxious arousal was associated with reduced SCR during unpredictable threat and lower P3 amplitudes across conditions. Intolerance of uncertainty modulated startle particularly in controls, and anxious apprehension was associated with increased N1 amplitudes in OCD. Exploratory latent profile analysis identified three multisystem physiological response profiles. A threat-reactive profile characterized by increased N1 and both increased SCR and startle to unpredictable threat was particularly clinically enriched, showing higher clinical severity, greater representation of SAD and OCD, and elevated anxious apprehension and social anxiety symptoms. Together, findings suggest that threat anticipation in anxiety-related psychopathology is best understood as a multisystem and partly transdiagnostic process rather than as a single physiological marker of diagnostic status or unpredictable-threat sensitivity.