Neurobehavioral Changes in Fear Generalization in Clinical High Risk for Psychosis

Jacqueline A Clauss; Baktash Babadi; Lauri Tuominen; Wisteria Deng; Logan Leathem; Daphne J Holt

doi:10.64898/2026.01.14.26344102

Changes in basic associative learning processes have been identified in several psychiatric conditions. However, it remains unknown whether these findings result from ongoing psychopathology or represent an underlying transdiagnostic risk factor for multiple clinical states. In this study, 72 participants with subclinical psychopathology, 23 of whom met criteria for the clinical high-risk for psychosis transdiagnostic risk syndrome (CHR+), completed a fear conditioning and generalization paradigm while functional magnetic resonance imaging (fMRI) data were collected. During this procedure, participants were presented with face stimuli that were either paired (CS+) or not paired (CS-) with a mild electrical shock, as well as eight face "morphs" (between the CS+ and CS-) tailored to each participant's perceptual discrimination ability. Following the scan session, participants rated the likelihood that each stimulus had been previously followed by a shock. Fear generalization-related neural responses and the memory ratings were then examined using both categorical and individual-level, psychometric modeling approaches. Expected patterns of fear generalization-related responses were observed in the anterior insula and superior frontal gyrus, and in the memory ratings. The psychometric modeling analysis revealed a significantly greater threshold in responses of the left anterior insula, representing a wider fear generalization curve, in the CHR+, compared to the control, group. Moreover, across the whole sample, symptoms of anxiety were associated with a wider fear generalization threshold. Thus, these findings suggest that specific features of one basic associative memory process, fear generalization, may be linked to CHR status and transdiagnostic risk for psychiatric illness.Changes in basic associative learning processes have been identified in several psychiatric conditions. However, it remains unknown whether these findings result from ongoing psychopathology or represent an underlying transdiagnostic risk factor for multiple clinical states. In this study, 72 participants with subclinical psychopathology, 23 of whom met criteria for the clinical high-risk for psychosis transdiagnostic risk syndrome (CHR+), completed a fear conditioning and generalization paradigm while functional magnetic resonance imaging (fMRI) data were collected. During this procedure, participants were presented with face stimuli that were either paired (CS+) or not paired (CS-) with a mild electrical shock, as well as eight face "morphs" (between the CS+ and CS-) tailored to each participant's perceptual discrimination ability. Following the scan session, participants rated the likelihood that each stimulus had been previously followed by a shock. Fear generalization-related neural responses and the memory ratings were then examined using both categorical and individual-level, psychometric modeling approaches. Expected patterns of fear generalization-related responses were observed in the anterior insula and superior frontal gyrus, and in the memory ratings. The psychometric modeling analysis revealed a significantly greater threshold in responses of the left anterior insula, representing a wider fear generalization curve, in the CHR+, compared to the control, group. Moreover, across the whole sample, symptoms of anxiety were associated with a wider fear generalization threshold. Thus, these findings suggest that specific features of one basic associative memory process, fear generalization, may be linked to CHR status and transdiagnostic risk for psychiatric illness.

Neurobehavioral Changes in Fear Generalization in Clinical High Risk for Psychosis

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