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Testing the role of belief updating in persecutory delusions

Award Number: R01MH137024
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/05/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Testing the role of belief updating in persecutory delusions - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $816,761 )
2026	2026	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	3	5/20/2026	NON-COMPETING CONTINUATION	$816,761
														Subtotal = $816,761

Issue Date FY: 2025 ( Subtotal = $812,911 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	2	6/3/2025	NON-COMPETING CONTINUATION	$812,911
2025	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	1	5/8/2025	NEW	$0
														Subtotal = $812,911

Issue Date FY: 2024 ( Subtotal = $717,736 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	1	7/5/2024	NEW	$717,736
														Subtotal = $717,736

Grand Total All Awards = $2,347,408

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Testing the role of belief updating in persecutory delusions

Award Number: R01MH137024

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/05/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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