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An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder.

ABSTRACT: Obsessive-compulsive disorder is treated with exposure with response prevention (ERP) therapy, in which patients are repeatedly exposed to compulsive triggers but prevented from expressing their compulsions. Many compulsions are an attempt to avoid perceived dangers, and the intent of ERP is to extinguish compulsions. Patients failing ERP therapy are candidates for deep brain stimulation (DBS) of the ventral capsule/ventral striatum, which facilitates patients' response to ERP therapy. An animal model of ERP would be useful for understanding the neural mechanisms of extinction in obsessive-compulsive disorder.Using a platform-mediated signaled avoidance task, we developed a rodent model of ERP called extinction with response prevention (Ext-RP), in which avoidance-conditioned rats are given extinction trials while blocking access to the avoidance platform. Following 3 days of Ext-RP, rats were tested with the platform unblocked to evaluate persistent avoidance. We then assessed if pharmacologic inactivation of lateral orbitofrontal cortex (lOFC) or DBS of the ventral striatum reduced persistent avoidance.Following Ext-RP training, most rats showed reduced avoidance at test (Ext-RP success), but a subset persisted in their avoidance (Ext-RP failure). Pharmacologic inactivation of lOFC eliminated persistent avoidance, as did DBS applied to the ventral striatum during Ext-RP.DBS of ventral striatum has been previously shown to inhibit lOFC activity. Thus, activity in lOFC, which is known to be hyperactive in obsessive-compulsive disorder, may be responsible for impairing patients' response to ERP therapy.

SUBMITTER: Rodriguez-Romaguera J

PROVIDER: S-EPMC4988932 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder.

Rodriguez-Romaguera Jose J Greenberg Benjamin D BD Rasmussen Steven A SA Quirk Gregory J GJ

Biological psychiatry 20160217 7

<h4>Background</h4>Obsessive-compulsive disorder is treated with exposure with response prevention (ERP) therapy, in which patients are repeatedly exposed to compulsive triggers but prevented from expressing their compulsions. Many compulsions are an attempt to avoid perceived dangers, and the intent of ERP is to extinguish compulsions. Patients failing ERP therapy are candidates for deep brain stimulation (DBS) of the ventral capsule/ventral striatum, which facilitates patients' response to ERP ...[more]

PMID: 27086546

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Project description:Background: Subtle differences in white matter microstructure have been found in obsessive-compulsive disorder (OCD) compared to controls using diffusion tensor imaging (DTI), but it is unclear if and how this change after treatment. The primary aim of this pre-registered study was to investigate white matter integrity between OCD patients and controls and changes after concentrated exposure and response prevention (ERP). Methods: Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) were estimated using FMRIB Software Library (FSL). The images were registered to a study-specific template using a longitudinal pipeline based on full tensor information in DTI-TK. Voxel-based analysis was performed using tract-based spatial statistics (TBSS). Using SPSS, we compared the integrity in three bilateral regions of interest (ROI), the sagittal stratum, posterior thalamic radiation and cingulum, in 32 OCD patients and 30 matched healthy controls at baseline. Patients received a four-day concentrated ERP format. We investigated longitudinal changes in 26 OCD patients and 22 healthy controls at 3months follow-up using repeated-measures ANOVA. Exploratory t-tests were conducted for AD and MD. Secondary hypothesis used linear regression to investigate if baseline FA predict treatment outcome 3 months later, and if patients with illness onset before 18 years of age would show lower FA in sagittal stratum. Finally, we performed sensitivity analysis on medication and comorbidity influences on FA. Results: Three months after treatment, 77% of the patients were in remission. Contrary to our hypotheses, we did not find any significant differences in FA, RD, AD or MD between the groups before treatment, nor significant group by time effects in any of the ROI. None of the baseline FA measures significantly predicted treatment outcome. Illness onset before 18 years of age did not significantly predict FA in the sagittal stratum. Adjusting for medication or comorbid anxiety or mood disorder did not influence the results. Conclusions: Although concentrated ERP in OCD lead to high remission, we did not find significant long-term changes by DTI. Future studies will benefit from using larger sample sizes and multi-shell diffusion-weighted imaging when investigating white matter microstructure in OCD and underlying neurobiological mechanisms of treatment.

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An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder.

Publications

An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder.

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