Ryan J. Jacoby , Jennifer L. Greenberg , Aura Hurtado , Walker Pedersen , Kristen K. Ellard , Edward F. Pace-Schott , Katelyn I. Oliver , Mohammed R. Milad , Sabine Wilhelm , Joan A. Camprodon
{"title":"强迫症暴露和反应预防的神经机制:一项随机对照试验","authors":"Ryan J. Jacoby , Jennifer L. Greenberg , Aura Hurtado , Walker Pedersen , Kristen K. Ellard , Edward F. Pace-Schott , Katelyn I. Oliver , Mohammed R. Milad , Sabine Wilhelm , Joan A. Camprodon","doi":"10.1016/j.brat.2025.104858","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Fear extinction is an important treatment target of obsessive-compulsive disorder (OCD). In the current randomized controlled trial, we examined the therapeutic modulation of exposure and response prevention (ERP) on neural activation during fear extinction in OCD to identify mechanisms of action and response biomarkers.</div></div><div><h3>Methods</h3><div>Thirty-four patients with OCD were randomized to either 12-weeks of ERP or a waitlist. Before, during, and 12-weeks after treatment, patients were assessed using functional magnetic resonance imaging (fMRI) during a 2-day fear extinction paradigm. Neural activation was examined in disease- and construct-relevant circuits and nodes (<em>n</em> = 18).</div></div><div><h3>Results</h3><div>The ERP group had a significant reduction in OCD severity compared to waitlist. A voxel-wise GLM analysis of fMRI data revealed clusters of ERP > waitlist activation during fear conditioning (bilateral dorsal amygdala and right hippocampus) and extinction (right ventrolateral prefrontal cortex, located within the salience network). These changes in activation did not correlate with OCD severity changes, however. In contrast, we observed that a reduction in the activation of the left supramarginal gyrus (in the executive control network) during extinction recall correlated with OCD symptom improvement, suggesting a possible role as a response biomarker.</div></div><div><h3>Conclusions</h3><div>This study highlights the relevance of a dimensional approach (e.g., focused on fear extinction) for biomarker discovery in neuropsychiatry, provides insights into the mechanisms of action of ERP in OCD, and identifies a potential treatment target in the parietal cortex that could support the biomarker-driven development of novel therapies (e.g., brain stimulation protocols), including combination treatments with ERP.</div></div><div><h3>Clinicaltrials.gov identifier</h3><div>NCT02467374.</div></div>","PeriodicalId":48457,"journal":{"name":"Behaviour Research and Therapy","volume":"194 ","pages":"Article 104858"},"PeriodicalIF":4.5000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neural mechanisms underlying exposure and response prevention for obsessive compulsive disorder: A randomized controlled trial\",\"authors\":\"Ryan J. 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Neural activation was examined in disease- and construct-relevant circuits and nodes (<em>n</em> = 18).</div></div><div><h3>Results</h3><div>The ERP group had a significant reduction in OCD severity compared to waitlist. A voxel-wise GLM analysis of fMRI data revealed clusters of ERP > waitlist activation during fear conditioning (bilateral dorsal amygdala and right hippocampus) and extinction (right ventrolateral prefrontal cortex, located within the salience network). These changes in activation did not correlate with OCD severity changes, however. 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Neural mechanisms underlying exposure and response prevention for obsessive compulsive disorder: A randomized controlled trial
Background
Fear extinction is an important treatment target of obsessive-compulsive disorder (OCD). In the current randomized controlled trial, we examined the therapeutic modulation of exposure and response prevention (ERP) on neural activation during fear extinction in OCD to identify mechanisms of action and response biomarkers.
Methods
Thirty-four patients with OCD were randomized to either 12-weeks of ERP or a waitlist. Before, during, and 12-weeks after treatment, patients were assessed using functional magnetic resonance imaging (fMRI) during a 2-day fear extinction paradigm. Neural activation was examined in disease- and construct-relevant circuits and nodes (n = 18).
Results
The ERP group had a significant reduction in OCD severity compared to waitlist. A voxel-wise GLM analysis of fMRI data revealed clusters of ERP > waitlist activation during fear conditioning (bilateral dorsal amygdala and right hippocampus) and extinction (right ventrolateral prefrontal cortex, located within the salience network). These changes in activation did not correlate with OCD severity changes, however. In contrast, we observed that a reduction in the activation of the left supramarginal gyrus (in the executive control network) during extinction recall correlated with OCD symptom improvement, suggesting a possible role as a response biomarker.
Conclusions
This study highlights the relevance of a dimensional approach (e.g., focused on fear extinction) for biomarker discovery in neuropsychiatry, provides insights into the mechanisms of action of ERP in OCD, and identifies a potential treatment target in the parietal cortex that could support the biomarker-driven development of novel therapies (e.g., brain stimulation protocols), including combination treatments with ERP.
期刊介绍:
The major focus of Behaviour Research and Therapy is an experimental psychopathology approach to understanding emotional and behavioral disorders and their prevention and treatment, using cognitive, behavioral, and psychophysiological (including neural) methods and models. This includes laboratory-based experimental studies with healthy, at risk and subclinical individuals that inform clinical application as well as studies with clinically severe samples. The following types of submissions are encouraged: theoretical reviews of mechanisms that contribute to psychopathology and that offer new treatment targets; tests of novel, mechanistically focused psychological interventions, especially ones that include theory-driven or experimentally-derived predictors, moderators and mediators; and innovations in dissemination and implementation of evidence-based practices into clinical practice in psychology and associated fields, especially those that target underlying mechanisms or focus on novel approaches to treatment delivery. In addition to traditional psychological disorders, the scope of the journal includes behavioural medicine (e.g., chronic pain). The journal will not consider manuscripts dealing primarily with measurement, psychometric analyses, and personality assessment.