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Behavioral and fMRI Evidence for Impaired Fear Generalization in Psychosis Risk
Abstract   Peer reviewed

Behavioral and fMRI Evidence for Impaired Fear Generalization in Psychosis Risk

Jacqueline Clauss, Lauri Tuominen, Rachel Sussman, Yushan Deng, Logan Leatham and Daphne Holt
Biological psychiatry (1969), Vol.95(10 Suppl), pp.S66-S66
05/15/2024
DOI: 10.1016/j.biopsych.2024.02.162

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Abstract

Background Psychotic disorders have been associated with impairments in basic associative learning processes, including fear generalization. However, it remains to be clarified if these deficits are a result of ongoing symptoms or if they represent an underlying risk factor for these symptoms. Methods Seventy-two subjects with subclinical psychopathology were enrolled; 23 met criteria for a psychosis risk syndrome (PRS). Subjects completed a Pavlovian fear conditioning and generalization paradigm in a 3T MRI scanner during which an unconditioned stimulus (shock) was paired (CS+) or not paired (CS-) with a face image. During a subsequent fear generalization phase, subjects were presented with eight faces that included morphs between the CS+ and CS-. After the scanning, subjects rated the likelihood that each stimulus had been followed by a shock. Functional activation to the stimuli was extracted from regions of interest defined in a prior fear generalization dataset. Results There were significant interactions of group x morph for both the shock likelihood ratings and insula activation (all p < 0.05), due to lower fear generalization in the PRS group; the PRS patients were less likely to rate CS+-like stimuli as followed by a shock (F(9, 630)=1.91, p = 0.048) and showed less activation in the left insula (F(9, 486)=1.81, p = 0.01). Moreover, the reduction in behavioral fear generalization was linked to anhedonia in the PRS group (r=0.43, p=0.038). Conclusions Individuals with risk for psychosis show impairments in fear generalization, suggesting that deficits in associative learning may occur early in the development of psychotic disorders.

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