Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder.

S Kohl,D Huys,F Jessen,L Timmermann,M Vorderwulbecke,V Visser-Vandewalle,T A Dembek,J Klosterkoetter,V Sturm,T O J Gruendler,E Sildatke,S E Ahmari,M Hellmich,J Kuhn

doi:10.1038/tp.2015.171

Abstract

Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.

Highlights

Obsessive-compulsive disorder (OCD) is one of the most prevalent and disabling of all psychiatric illnesses.[1]
Post hoc comparisons indicated that the tr-obsessive-compulsive disorder (OCD) group with deep brain stimulation (DBS) off (47.3 ± 12.8, P = 0.001) and the by nucleus accumbens (NAcc).[19]
prepulse inhibition (PPI) is a paradigm of high translational relevance, as it is disrupted in many psychiatric disorders, and PPI disruptions are even considered by some authors to be an endophenotype in schizophrenia.[20]

Summary

Introduction

Obsessive-compulsive disorder (OCD) is one of the most prevalent and disabling of all psychiatric illnesses.[1] Core symptoms of OCD are anxiety, provoking recurrent and intrusive thoughts or images (obsessions) and repetitive and ritualistic behaviors (compulsions) that are time consuming in nature Cognitive behavioral therapy and selective serotonin reuptake inhibitors are the most effective treatment options available. About 10% of all patients, profit neither from pharmacological nor from psychological treatments.[2] It has been suggested that these treatmentrefractory OCD patients (tr-OCD) might benefit from deep brain stimulation (DBS), a stereotactic, neuromodulative procedure that delivers chronic and high frequency stimulation in subcortical regions of the brain.[3] Since 1999, ~ 200 otherwise treatmentrefractory patients suffering from OCD underwent stereotactic surgery.[4] the most optimal stimulation point is still being determined, DBS for OCD has led to significant symptom reductions in most tr-OCD patients up to this point (for a review, see Kohl et al.[5]). Based on the largest data set, and taking into account the severe nature of tr-OCD, the FDA

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