Persecutory ideation occurs across multiple neuropsychiatric disorders; it can be resistant to treatment, and is associated with prominent negative affect as well as an increased risk of violent acts. The biological substrates currently remain unclear although two main systems have been proposed as the underlying neurobiology: frontal-striatal regions, and separately, temporo-parietal regions. Recent theories of brain functioning suggest rather than isolated regions or systems, complex behaviors may be better represented by a combination of local and global connections between distinct brain regions. Therefore, a thorough examination of how large- scale neural connectivity is associated with delusional ideation is warranted to increase understanding of the etiology. Using the Minnesota Trust Game, a novel variant of the Prisoner's Dilemma Game, the project will employ a functional connectivity approach to assess both the intra- and inter-network connectivity contributions to the neural architecture involved in suspiciousness. Analyses will target connectivity metrics associated with the theorized frontal-striatal and temporo-parietal regions to evaluate the degree to which these systems are engaged during the task, and the capacity for derived metrics to predict individual differences in persecutory ideation. The first primary goal i to develop a theory driven biomarker of suspiciousness by investigating functional magnetic resonance data from a sample of schizophrenia patients and a sample of community dwelling monozygotic twins who played the Minnesota Trust Game while in the scanner. This includes assessment of the external validation of the biomarker by examining associations with individual differences in persecutory ideation, or alienation which is an approximation of psychosis-like experiences in community participants. It also includes investigating whether discordance in connectivity metrics predicts discordance in personality traits in twins. The second primary goal is to test generalizability of the biomarker by evaluating the capacity of corresponding connectivity metrics, derived from resting-state, to predict similar relationships with individual differences in persecutory ideation in a separate sample of schizophrenia patients and controls. Follow-up analyses will evaluate the specificity of these associations. Furthermore, the capacity of the networks to distinguish patients from controls, and moreover, first-episode from chronic patients will also be investigated. Through this work procedures may identify connectivity hubs which appear to be critical for the experience of persecutory ideation, and thus could be employed as targets for future treatments and biomarkers to identify those at risk for these distressing beliefs.

Public Health Relevance

Persecutory ideation occurs across multiple neuropsychiatric disorders; it can be resistant to treatment, and is associated with prominent negative emotionality as well as an increased risk of violent acts. Although the etiology of persecutory delusions is debated, the biological substrates remain unclear. Novel research designed to elucidate the specific etiology could aid development of treatments sensitive to the specific brain dysfunctions involved in creating and perpetuating these distressing beliefs.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Chavez, Mark
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University of Minnesota Twin Cities
Schools of Arts and Sciences
United States
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