# Testing the role of belief updating in persecutory delusions

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $717,736

## Abstract

Persecutory delusions, or the strongly held belief that others intend me harm, are distressing and disabling
transdiagnostic symptoms. They are the most common manifestation of delusions in psychotic disorders,
present in over 70% of cases, and exist at the extreme end of the paranoia spectrum. Persecutory delusions
are a leading cause of suicidal ideation and hospitalization amongst individuals with schizophrenia, yet
effective, sustainable treatments remain limited. One potential route towards developing new treatments is
identification of cognitive processes that directly contribute their maintenance. Predictive coding is a prominent
mechanistic account of delusions based in the process of belief updating, which describes how we learn about
the world and develop new beliefs. Development of adaptive, rational beliefs depends on an accurate
understanding of the volatility of the environment, or how frequently the probabilities underlying the
environment change. Over-estimation of volatility (i.e. inferring that the environment has changed when it has
not) drives the formation of new beliefs that are based on faulty inference. There is growing support that
aspects of volatility-related belief updating contribute to paranoia and persecutory delusions specifically.
Longitudinal data from the PI’s K23 newly demonstrate that volatility-related belief updating is abnormal in
delusional patients with schizophrenia, normalizes with symptom improvement, and is associated with
activation in specific brain regions. Yet, these data remain limited by their correlational nature. Randomized
controlled trials are the gold standard of causal inference testing, drawing more definitive conclusions about
mechanism. Therefore, to push this research forward and directly test the belief updating model of delusions,
we will recruit 120 individuals with a schizophrenia-spectrum disorder endorsing a persistent persecutory
delusion and randomize them to receive either formulation-driven cognitive-behavioral therapy for persecutory
delusions (CBTp), which has been previously shown to reduce delusion severity, or an active control therapy
(befriending). We will then test whether modification of persecutory delusion severity using psychotherapy
impacts belief updating at the level of behavior (Aim 1) and neurobiology (Aim 2), investigating specific brain
circuits underlying distinct volatility parameters. Our ultimate goal is to leverage the insights gained into new,
mechanistically informed treatments for persecutory delusions and paranoia, translating computational
neuroscience to clinical applications.

## Key facts

- **NIH application ID:** 10939484
- **Project number:** 1R01MH137024-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Julia May Sheffield
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $717,736
- **Award type:** 1
- **Project period:** 2024-07-05 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939484

## Citation

> US National Institutes of Health, RePORTER application 10939484, Testing the role of belief updating in persecutory delusions (1R01MH137024-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10939484. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*