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Randomized Controlled Trial
. 2025 Jun 2;8(6):e2517132.
doi: 10.1001/jamanetworkopen.2025.17132.

Prior Expectations of Volatility Following Psychotherapy for Delusions: A Randomized Clinical Trial

Julia M Sheffield  1 , Ali F Sloan  2 , Philip R Corlett  3 , Baxter P Rogers  4 , Simon Vandekar  5 , Jinyuan Liu  5 , Kendall M Beals  6 , Lauren M Hall  7 , Taylor Gautier  8 , Alexandra B Moussa-Tooks  9 , Lénie J Torregrossa  10 , Margaret Achee  1 , Kristan Armstrong  1 , Neil D Woodward  1 , Kaylee Belt  11 , Daniel Freeman  12 , Louise Isham  12 , Rowan Diamond  12 , Aaron P Brinen  1 , Stephan Heckers  1
Affiliations
Randomized Controlled Trial

Prior Expectations of Volatility Following Psychotherapy for Delusions: A Randomized Clinical Trial

Julia M Sheffield et al. JAMA Netw Open. .

Abstract

Importance: Persecutory delusions are common, distressing, and difficult to treat. Testing computational neuroscience models of delusions can identify new therapeutic targets.

Objective: To determine whether change in delusion severity is associated with a corresponding change in volatility priors and brain activation estimated during a belief updating task.

Design, setting, and participants: This randomized clinical trial was conducted from April 9, 2021, to December 5, 2023, within the Vanderbilt University Medical Center Psychiatric Hospital and at a community mental health center in Nashville, Tennessee. Participants were adults (aged between 18 and 65 years) with schizophrenia spectrum or delusional disorder and an active, persistent (≥3 months) persecutory delusion with strong conviction (>50%). Participants were randomly assigned 1:1 to either cognitive behavioral therapy for psychosis (CBTp)-based intervention or befriending therapy. Intention-to-treat analysis was performed from June 1 to October 31, 2024.

Intervention: The CBTp was a manualized intervention targeting persecutory delusions. The befriending therapy involved engaging in conversations and activities focused on neutral topics. Both interventions were provided in person, lasted for 8 weeks, and included standard care. Standard care consisted of medication management and ancillary services.

Main outcomes and measures: Primary outcomes were volatility priors (ie, prior expectations of volatility) derived from a 3-option probabilistic reversal learning task; persecutory delusion severity measured by the Psychotic Symptom Rating Scales (PSYRATS delusion subscale; score range: 0-16, with the highest score indicating severe preoccupation, distress, conviction, and functioning impact); and brain activation in the striatum and prefrontal cortex measured by blood oxygenation level-dependent signal change. Associations between volatility priors, clinical improvement, and change in neural activation were examined.

Results: Sixty-two participants (median [range] age, 31 [19-63] years; 38 males [61%]) were randomly assigned to the CBTp (n = 32) or befriending therapy (n = 30) arms. A subgroup of 35 participants (57%) completed functional magnetic resonance imaging. Volatility priors decreased following treatment (F1,112 = 7.7 [P = .006]; Cohen d = 0.52 [95% CI, 0.15-0.90]), as did delusion severity (F1,112 = 59.7 [P < .001]; Cohen d = 1.50 [95% CI, 1.00-1.90]), across both groups. The decrease in volatility priors was not associated with clinical improvement in PSYRATS scores (F1,102.8 = 1.8 [P = .18]; Cohen d = 0.26 [95% CI, -0.12 to 0.65]). Activation in the caudate and prefrontal cortex significantly decreased following treatment. Decreased caudate activation was associated with decreased volatility priors (F1,58.3 = 16.6 [P < .001]; Cohen d = 1.07 [95% CI, 0.51-1.61]) but not with PSYRATS total scores. Associations remained significant after controlling for antipsychotic medication (F1,53 = 13.77; P < .001).

Conclusions and relevance: This randomized clinical trial found that elevated volatility priors and associated activation in the caudate nucleus were amenable to change. Volatility priors could be a potential target for intervention in psychosis.

Trial registration: ClinicalTrials.gov Identifier: NCT04748679.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Corlett reported being a cofounder and board member of Tetricus Labs outside the submitted work. Dr Moussa-Tooks reported receiving support from the National Institute of Mental Health (NIMH) during the conduct of the study. Dr Freeman reported being the original developer of the treatment used in the study and the Feeling Safe Program outside the submitted work. Dr Brinen reported being a cofounder of North Shore Therapeutics outside the submitted work. Dr Heckers reported receiving grants from the NIMH during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Trial Flow Diagram
CBTp indicates cognitive behavioral therapy for psychosis; MRI, magnetic resonance imaging; PSWQ, Penn State Worry Questionnaire.
Figure 2.
Figure 2.. Change in Clinical Outcomes With Psychotherapy
CBTp indicates cognitive behavioral therapy for psychosis; PANSS, Positive and Negative Syndrome Scale, Positive Subscale; PSYRATS, Psychotic Symptom Rating Scales.
Figure 3.
Figure 3.. Change in Volatility Priors With Psychotherapy and Association With Positive and Negative Syndrome Scale (PANSS) Positive Symptoms
Figure 4.
Figure 4.. Change in Functional Magnetic Resonance Imaging Activation and Association With Volatility Priors and Positive and Negative Syndrome Scale (PANSS) Positive Symptoms
Error bars represent SEs of the mean. BLOD indicates blood oxygenation level–dependent; PFC, prefrontal cortex.
See this image and copyright information in PMC

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