A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Body Dysmorphic Disorder in aesthetic rhinoplasty: Validating a new screening tool.

OBJECTIVES/HYPOTHESIS: To validate a new screening tool for body dysmorphic disorder (BDD) in patients seeking aesthetic rhinoplasty. STUDY DESIGN: We performed a prospective instrument validation study in an academic rhinology clinic. METHODS: The Body Dysmorphic Disorder Questionnaire-Aesthetic Surgery (BDDQ-AS) is a seven-item short questionnaire validated in 116 patients undergoing aesthetic rhinoplasty. Screening was positive if the patient acknowledged on the BDDQ-AS that he/she was concerned about their appearance (question 1 = yes) AND preoccupied with these concerns (question 2 = yes) AND that these concerns caused at least moderate distress or impairment in different domains of daily life (question 3 or 4 or 5 or 6 ≥ 3 or question 7 = yes). Construct validity was assessed by comparing the BDDQ-AS to the Sheehan Disability Scale and the Derriford Appearance Scale-59. To determine concurrent validity, the BDDQ-AS was compared to the Yale-Brown Obsessive Compulsive Scale Modified for BDD. Finally, the predictive value of the BDDQ-AS on satisfaction 12 months after rhinoplasty was evaluated using a visual analogue scale and the Rhinoplasty Outcome Evaluation. RESULTS: Reliability of the BDDQ-AS was adequate, with Cronbach alpha = .83 for rhinoplasty patients and .84 for controls. Sensitivity was 89.6% and specificity 81.4%. BDDQ-AS-positive patients (n = 55) were more impaired in daily life and experienced more appearance-related distress and dysfunction compared to BDDQ-AS-negative patients. Moreover, they had more severe BDD symptoms. Finally, BDDQ-AS-positive patients were less satisfied after surgery compared to BDDQ-AS-negative patients. CONCLUSIONS: We hereby validated a new screening tool for BDD in an aesthetic rhinoplasty population. LEVEL OF EVIDENCE: 3b. Laryngoscope, 126:1739-1745, 2016.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response.

BACKGROUND: Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. METHODS: We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. FINDINGS: Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas--anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate--27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. CONCLUSIONS: Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome.

Deep Brain Stimulation for Obsessive Compulsive Disorder Reduces Symptoms of Irritable Bowel Syndrome in a Single Patient.

Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder that is difficult to treat. We describe findings from evaluation of a woman (55 years old) with obsessive compulsive disorder, which was treated with bilateral deep brain stimulation in the anterior limb of the internal capsule, and IBS. After the brain stimulation treatment she reported substantial relief of her IBS symptoms. This reduction depended on specific stimulation parameters, was reproducible over time, and was not directly associated with improvements in obsessive compulsive disorder symptoms. These observations indicate a specific effect of deep brain stimulation on IBS. This observation confirms involvement of specific brain structures in the pathophysiology of IBS and shows that symptoms can be reduced through modulation of neuronal activity in the central nervous system. Further studies of the effects of brain stimulation on IBS are required.

Differences in metabolic network modulation between capsulotomy and deep-brain stimulation for refractory obsessive-compulsive disorder.

UNLABELLED: Around 7%-10% of patients with obsessive-compulsive disorder (OCD) are refractory to first-line treatment. Neurosurgical approaches are available such as capsulotomy or deep-brain stimulation (DBS). There is strong evidence for central involvement of the corticostriatopallidothalamocortical (CSPTC) circuit in OCD, but the exact mechanism through which these interventions lead to clinical improvement and potential differences in network modulation are not fully understood. METHODS: In total, 13 capsulotomy patients (aged 29-59 y, 10 men and 3 women) and 16 DBS patients (aged 25-56 y, 6 men and 10 women) were prospectively included. (18)F-FDG PET was performed before and after capsulotomy and before and after DBS in both stimulation-on and stimulation-off conditions. Presurgical scans were compared with scans of healthy volunteers using SPM8 and global scaling, and metabolic changes after DBS were compared with changes after capsulotomy. Correlations with clinical improvements were investigated using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HAM-D). RESULTS: Both groups had similar pretreatment clinical morbidity as assessed by Y-BOCS and the Hamilton Depression Rating Scale. Preoperative superior frontal and supplementary motor cortex hypometabolism was common to both patient groups, and the subgenual anterior cingulate, occipital cortex (cuneus), and posterior cerebellum were relatively hypermetabolic. Postoperative metabolic decreases were common to both interventions in the anterior cingulate and the prefrontal and orbitofrontal cortices. Compared with DBS, capsulotomy resulted in more intense metabolic changes, with additional significant decreases in the mediodorsal thalamus, caudate nucleus, and cerebellum as well as increases in the precuneus and the fusiform and lingual gyrus. The stimulation-off condition of DBS patients showed no significant differences from the preoperative state. Improvement in Y-BOCS scores correlated with metabolic changes in the occipital cortex. Baseline metabolism in the subgenual anterior cingulate and superior temporal cortices were related to postoperative improvement of depressive symptoms. CONCLUSION: Capsulotomy and DBS lead to similar clinical improvement and similar metabolic network changes in the CSPTC circuit, with a prominent role for the subgenual anterior cingulate and other core structures of the CSPTC. However, metabolic changes are more pronounced and extended in capsulotomy than in DBS. Furthermore, cortical regions outside the CSPTC may also play an important role in OCD symptomatology.

Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders.

BACKGROUND: For patients with psychiatric illnesses remaining refractory to 'standard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. METHODS: To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. FINDINGS: The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered 'established' in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-up evaluation, and reporting of effects and side effects for all patients. INTERPRETATION: This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.

Obsessive-compulsive behavior as presenting symptom of primary antiphospholipid syndrome.

OBJECTIVE: This study aimed to improve understanding and treatment of psychiatric symptoms in antiphospholipid syndrome (APS) and to present an approach to the medical management of patients presenting with obsessive-compulsive disorder (OCD) with suspected neurovascular pathology. METHOD: A 15-year-old boy presented with severe OCD of recent onset. An infarct of the caudate nucleus was identified as the initial presentation of primary APS. This case report includes a selective literature review of the neuropsychiatric correlates of APS. RESULTS: The patient had OCD for 3 months with increasing symptoms resulting in admission for psychiatric reasons. After referral to the emergency department 3 weeks later, an infarct of the caudate nucleus was documented using magnetic resonance images of the brain, and APS was diagnosed based on additional laboratory findings. Anticoagulant treatment (enoxaparin and phenprocoumon) in this patient was effective in reducing obsessive-compulsive symptom severity. CONCLUSION: OCD may present as a neuropsychiatric manifestation of APS. The present observations are consistent with a thrombotic mechanism for neurologic or psychiatric symptoms in APS. In general, routine medical workup for childhood OCD is not indicated, but a comprehensive psychiatric, medical, and family history taking and physical examination are essential, particularly if OCD is of recent onset. The role of anticoagulant therapy in neuropsychiatric manifestations of APS without the presence of a cerebral infarct requires further research.

Targeting bed nucleus of the stria terminalis for severe obsessive-compulsive disorder: more unexpected lead placement in obsessive-compulsive disorder than in surgery for movement disorders.

BACKGROUND: In preparation for a multicenter study, a protocol was written on how to perform surgical targeting of the bed nucleus of the stria terminalis, based on the lead implantation experience in patients with treatment-refractory obsessive-compulsive disorder (OCD) at the Universitaire Ziekenhuizen Leuven (UZ Leuven). When analyzing the postoperative images, we were struck by the fact that the difference between the postoperative position of the leads and the planned position seemed larger than expected. METHODS: The precision of targeting in four patients with severe OCD who received bilateral model 3391 leads (Medtronic) was compared with the precision of targeting in the last seven patients who underwent surgery at UZ Leuven for movement disorders (four with Parkinson disease and three with essential tremor; all received bilateral leads). Because the leads implanted in six of the seven patients with movement disorders were model 3387 leads (Medtronic), targeting precision was also analyzed in four patients with OCD in whom model 3387 leads were implanted in the same target as the other patients with OCD. RESULTS: In the patients with OCD, every implanted lead deviated at least 1.3 mm from its intended position in at least one of three directions (lateral, anteroposterior, and depth), whereas in the patients with movement disorders, the maximal deviation of any of all implanted leads was 1.3 mm. The deviations in lead placement were comparable in patients with OCD who received a model 3387 implant and patients who received a model 3391 implant. In the patients with OCD, all leads were implanted more posteriorly than planned. CONCLUSIONS: The cause of the posterior deviation could not be determined with certainty. The most likely cause was an increased mechanical resistance of the brain tissue along the trajectory when following the targeting protocol compared with the trajectories classically used for subthalamic nucleus or ventral intermediate nucleus of the thalamus stimulation.

Deep-brain stimulation for anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a complex and severe, sometimes life-threatening, psychiatric disorder with high relapse rates under standard treatment. After decades of brain-lesioning procedures offered as a last resort, deep-brain stimulation (DBS) has come under investigation in the last few years as a treatment option for severe and refractory AN. METHODS AND RESULTS: In this jointly written article, Sun et al. (the Shanghai group) report an average of 65% increase in body weight in four severe and refractory patients with AN after they underwent the DBS procedure (average follow-up: 38 months). All patients weighed greater than 85% of expected body weight and thus no longer met the diagnostic criteria of AN at last follow-up. Nuttin et al. (the Leuven group) describe other clinical studies that provide evidence for the use of DBS for AN and further discuss patient selection criteria, target selection, and adverse event of this evolving therapy. CONCLUSION: Preliminary results from the Shanghai group and other clinical centers showed that the use of DBS to treat AN may be a valuable option for weight restoration in otherwise-refractory and life-threatening cases. The nature of this procedure, however, remains investigational and should not be viewed as a standard clinical treatment option. Further scientific investigation is essential to warrant the long-term efficacy and safety of DBS for AN.

Preoperative symptoms of body dysmorphic disorder determine postoperative satisfaction and quality of life in aesthetic rhinoplasty.

BACKGROUND: In patients seeking aesthetic rhinoplasty, a high prevalence of body dysmorphic disorder symptoms has recently been reported. However, the impact of these symptoms on the outcomes after rhinoplasty remains elusive. This large-scale study determines the influence of preoperative body dysmorphic disorder symptoms on patients' postoperative satisfaction and quality of life, using validated questionnaires. METHODS: A 1-year prospective study of 166 adult patients undergoing cosmetic rhinoplasty in a tertiary referral center was performed. Severity of body dysmorphic disorder symptoms was assessed by the modified Yale-Brown Obsessive Compulsive Scale. Postoperative satisfaction was evaluated using a visual analog scale for patients' appraisal of nasal shape and the Rhinoplasty Outcome Evaluation. Generic quality of life was quantified by the Sheehan Disability Scale, whereas the appearance-related disruption of everyday life was measured by the Derriford Appearance Scale-59. RESULTS: Preoperative body dysmorphic disorder symptom scores inversely correlated with postoperative satisfaction at 3 months (visual analog scale nasal shape: rho = -0.43, p < 0.001; Rhinoplasty Outcome Evaluation: rho = -0.48, p < 0.001) and 12 months (rho = -0.40, p < 0.001; and rho = -0.41, p < 0.001, respectively) after surgery. In addition, body dysmorphic disorder symptom scores positively correlated with Sheehan Disability Scale scores and Derriford Appearance Scale-59 scores at 3 months (rho = 0.43, p < 0.001 and rho = 0.48, p < 0.001, respectively) and 12 months (rho = 0.32, p < 0.001, and rho = 0.48, p < 0.001, respectively) postoperatively. CONCLUSION: This study provides the first evidence of the negative impact of preoperative body dysmorphic disorder symptoms on subjective outcomes after rhinoplasty, hence unveiling a crucial factor in patient dissatisfaction after aesthetic rhinoplasty.

Successful anterior capsulotomy in comorbid anorexia nervosa and obsessive-compulsive disorder: case report.

BACKGROUND AND IMPORTANCE: State-of-the-art treatment of anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) often proves ineffective. Both disorders have common features, and anterior capsulotomy is a last-resort treatment for OCD. We document the effect of bilateral anterior capsulotomy in a patient with comorbid AN and OCD. CLINICAL PRESENTATION: A 38-year-old woman with life-threatening, chronic, treatment-refractory AN and OCD underwent anterior capsulotomy. Psychiatric and neuropsychological evaluations at baseline and at follow-up document the severity and progress of the case. Bilateral anterior capsulotomy resulted in normalization of eating pattern and weight and a significant decrease of food-related and overall obsessive-compulsive symptoms. Psychiatric evaluations and exposure to food cues confirmed the clinical improvement that was evident immediately after surgery and sustained at 3-month follow-up. CONCLUSION: This case report suggests that bilateral anterior capsulotomy can be a therapeutic option for patients with comorbid AN and OCD. However, a well-controlled study is warranted.

Contextual conditioning in rats as an animal model for generalized anxiety disorder.

Animal models of psychiatric disorders are important translational tools for exploring new treatment options and gaining more insight into the disease. Thus far, there is no systematically validated animal model for generalized anxiety disorder (GAD), a severely impairing and difficult-to-treat disease. In this review, we propose contextual conditioning (CC) as an animal model for GAD. We argue that this model has sufficient face validity (there are several symptom similarities), predictive validity (it responds to clinically effective treatments), and construct validity (the underlying mechanisms are comparable). Although the refinement and validation of an animal model is a never-ending process, we want to give a concise overview of the currently available evidence. We suggest that the CC model might be a valuable preclinical tool to enhance the development of new treatment strategies and our understanding of GAD.

Deep brain stimulation for psychiatric disorders.

Research on DBS for psychiatric disorders is being carried out in several areas, including obsessive- compulsive disorder, major depression, addictions, Tourette's syndrome and eating disorders. The results in the literature are described. The need for rigorous screening by interdisciplinary and ethical teams is explained. The need for pooling patients across different centres, with common treatment protocols, in order to achieve necessary large-scale studies in psychiatric DBS with long-term follow-up is pointed out.

Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought.

CONTEXT: A 2-day consensus conference was held to examine scientific and ethical issues in the application of deep brain stimulation for treating mood and behavioral disorders, such as major depression, obsessive-compulsive disorder, and Tourette syndrome. OBJECTIVES: The primary objectives of the conference were to (1) establish consensus among participants about the design of future clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and (2) develop standards for the protection of human subjects participating in such studies. RESULTS: Conference participants identified 16 key points for guiding research in this growing field. CONCLUSIONS: The adoption of the described guidelines would help to protect the safety and rights of research subjects who participate in clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and have further potential to benefit other stakeholders in the research process, including clinical researchers and device manufactures. That said, the adoption of the guidelines will require broad and substantial commitment from many of these same stakeholders.

Towards a neurocircuitry in anorexia nervosa: evidence from functional neuroimaging studies.

Functional neuroimaging is widely used to unravel changes in brain functioning in psychiatric disorders. In the current study, we review single-photon emission tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in anorexia nervosa (AN), a difficult-to-treat eating disorder with the highest mortality rate among psychiatric disorders. We discuss the role of the parietal cortex, anterior and subgenual cingulate cortex, frontal cortex and temporal lobe in light of the cardinal symptoms of AN. The insights of the current review may ultimately lead to the development of new treatments.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision.

In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder.

OBJECTIVE: Because of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing, treatment-resistant obsessive-compulsive disorder. METHODS: We stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTS: The psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 +/- 8.0) than in the postoperative stimulator-off condition (mean, 32.3 +/- 3.9), and this stimulation-induced effect was maintained for at least 21 months after surgery. The Clinical Global Severity score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition to 3.3 (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies, especially in the pons. Digital subtraction analysis of preoperative [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSION: These observations indicate that capsular stimulation reduces core symptoms 21 months after surgery in patients with severe, long-standing, treatment-refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography.

Metabolic imaging of anterior capsular stimulation in refractory obsessive-compulsive disorder: a key role for the subgenual anterior cingulate and ventral striatum.

UNLABELLED: High-frequency anterior capsular stimulation is a new, promising, and reversible neuromodulatory treatment in the research stage for patients with refractory obsessive-compulsive disorder (OCD). The mechanism of action is unknown but hypothesized to be secondary to interruption of the corticothalamostriatocortical circuit. METHODS: (18)F-FDG PET was performed on 6 consecutive OCD patients preoperatively and after stimulation. The results were compared with those of 20 age- and sex-matched healthy volunteers by using both a standardized volume-of-interest-based approach for subcortical areas and statistical parametric mapping. Correlations were investigated with Yale-Brown Obsessive Compulsive Scale scores (Y-BOCS) and Hamilton Depression Rating Scale scores (HAM-D). RESULTS: Chronic anterior capsular electrostimulation resulted in a further decrease of prefrontal metabolic activity, especially in the subgenual anterior cingulate (P < 0.001). Correlation analysis demonstrated that decreases in Y-BOCS and HAM-D with anterior capsular electrostimulation were inversely related to the metabolic activity changes in the left ventral striatum, left amygdala, and left hippocampus (P < 0.01). Preoperative resting metabolic activity in the subgenual anterior cingulate was predictive of therapeutic response (P = 0.001). CONCLUSION: These observations provide evidence that the subgenual anterior cingulate and ventral striatum have a key role in the neuronal circuitry involved in the pathophysiology of OCD with associated major depression and in the neuromodulatory mechanism of anterior capsular stimulation.