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Persecutory ideation is a common and distressing symptom that exists on a continuum with persecutory delusions. Although associated with severe negative consequences the neural mechanisms underlying persecutory ideation remain unclear. Contributing factors in this research deficit include i) low rates of studies specifically examining persecutory ideation, favoring instead broader symptom measurement, and ii) a lack of paradigms that sufficiently engage or examine specific mechanisms associated with the symptom. In this dissertation, a wide range of literature is reviewed to identify brain regions consistently associated with delusions or positive symptoms in order to aid development of a model of persecutory ideation and stimulate research. Brain regions highlighted by the review represented a convergence of neurobiological models of delusions, and were the focus of two empirical studies. In the first study we employed a novel economic social decision-making task in two samples during neuroimaging. We demonstrated a dorsal anterior cingulate and anterior insula (dACC-AI) network, a left frontal-parietal (lF-P) network, and a ventral medial orbital prefrontal (vmPFC/OFC) network were associated with distinct forms of distrust. We then revealed only the connectivity between the vmPFC/OFC and lF-P networks predicted persecutory ideation, suggesting a role of weakened top-down control on subjective valuation. Moreover, we established this mechanism was associated with unique environmental influence in community monozygotic twins. In our second study we aimed to replicate the task-based finding in two resting-state samples to demonstrate generalizability of the mechanism; however, confirmatory analyses did not replicate. In summary, the posited vmPFC/OFC - lF-P interconnectivity mechanism of persecutory ideation appears to be uniquely evoked by the economic social decision-making task. While this provides a novel perspective on persecutory ideation, replications in larger samples are needed.