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Background: Spite sensitivity provides a valuable construct to understand persecutory ideation and its underlying neural mechanisms. We examined the relationship between persecution and spite sensitivity in psychosis to identify their neural substrates., Methods: In a 3T magnetic resonance imaging scanner, 49 participants with psychosis played the Minnesota Trust Game, in which they decided whether to take a small amount of money or trust a partner to choose between fair and unfair distributions of money. In some conditions, the partner benefited from the unfair option, while in others, the partner lost money. Participants who were untrusting in the second condition (suspiciousness) showed heightened sensitivity to spite. Behavioral measures included mistrust during the 2 conditions of the game, which were compared with Brief Psychiatric Rating Scale persecution and computational modeling. Functional connectivity and blood oxygen level-dependent analyses were also conducted on a priori regions during spite-sensitive decisions., Results: Behavioral results replicated previous findings; participants who experienced more persecutory ideation trusted less, specifically in the suspiciousness condition. Functional connectivity findings showed that decreased connectivity between the orbitofrontal cortex-insula and the left frontoparietal network was associated with increased persecutory ideation and estimated spite-guilt (a marker of spite sensitivity). Additionally, we found differences between conditions in caudate nucleus, medial prefrontal cortex, and lateral orbitofrontal cortex activation., Conclusions: These findings provide a new perspective on the origin of positive symptoms by identifying primary brain circuits that are related to both spite sensitivity and persecutory ideation., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)