Cyclic versus continuous deep brain stimulation in patients with obsessive compulsive disorder: A randomized controlled trial

BackgroundDeep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD), but patients typically require high stimulation voltages and DBS comes with a risk for adverse events (AE).ObjectiveThe aim of the present study was to advance DBS for OCD by optimizing energy efficiency and minimize adverse events using a cyclic form of stimulationMethodsThis double blind, randomized crossover trial compares 2 weeks of continuous versus cyclic DBS (0.1 s ON, 0.2 s OFF) in 16 patients with OCD. We compared OCD symptoms (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), AEs, battery life, cognitive performance and quality of life.ResultsAverage Y-BOCS scores at baseline increased significantly with 5.5 points (p = 0.006) in the cyclic condition. Average HAM-D and HAM-A scores increased with 2.2 (p = 0.088) and 2.8 points (p = 0.018). The overall health scale of quality of life worsened during cyclic DBS (p = 0.044). Patients reported on average 3.3 AEs during continuous stimulation and 4.4 AEs during cyclic stimulation (p = 0.175), though stimulation-related AEs such as headache and concentration problems reduced during cyclic DBS. Battery usage during continuous DBS was 0.021 V per hour compared to 0.008 V per hour during cyclic DBS.ConclusionThough specific stimulation-related AEs improved, cyclic stimulation (0.1 s ON, 0.2 s OFF) comes with a high relapse risk in patients with DBS for OCD. Cyclic DBS is no alternative for standard DBS treatment, but applicable in case of debilitating AEs.     

Dysregulation of neurosteroids in obsessive compulsive disorder

Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-h serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD.     

Deep brain stimulation of the anterior limb of the internal capsule for treatment of therapy-refractory obsessive compulsive disorder (OCD): a case study highlighting neurocognitive and psychiatric changes

Obsessive compulsive disorder (OCD) is an anxiety disorder characterized by repeated, unwanted thoughts and behaviors. Individuals with this condition often experience significant emotional distress secondary to their symptoms. Additionally, impairments in attention/concentration, processing speed, and executive functions are typically observed. The exact pathology of OCD remains unknown; consequently, it can be difficult to treat patients with severe symptomatology. Deep brain stimulation (DBS) may be a viable treatment option for individuals who do not respond to medication and/or cognitive behavioral therapy. The following case discusses DBS of the anterior limb of the internal capsule for a patient with severe, therapy-refractory OCD, including pre- to postoperative neurocognitive and psychiatric changes.     

High frequency stimulation and temporary inactivation of the subthalamic nucleus reduce quinpirole-induced compulsive checking behavior in rats

Obsessive-compulsive disorder (OCD) represents a highly prevalent and impairing psychiatric disorder. Functional and structural imaging studies implicate the involvement of basal ganglia-thalamo-cortical circuits in the pathophysiology of this disorder. In patients remaining resistant to pharmaco- and behavioral therapy, modulation of these circuits may consequently reverse clinical symptoms. High frequency stimulation (HFS) of the subthalamic nucleus (STN), an important station of the basal ganglia-thalamo-cortical circuits, has been reported to reduce obsessive-compulsive symptoms in a few Parkinson's disease patients with comorbid OCD. The present study tested the effects of bilateral HFS of the STN and of bilateral pharmacological inactivation of the STN (via intracranial administration of the GABA agonist muscimol) on checking behavior in the quinpirole rat model of OCD. We demonstrate that both HFS and pharmacological inactivation of the STN reduce quinpirole-induced compulsive checking behavior. We conclude that functional inhibition of the STN can alleviate compulsive checking, and suggest the STN as a potential target structure for HFS in the treatment of OCD.     

A systematic review of psychiatric indications for deep brain stimulation,with focus on major depressive and obsessive-compulsive disorder

Background: Deep brain stimulation is a treatment under investigation for a range of psychiatric disorders. It has shown promising results for therapy-refractory obsessive–compulsive disorder (OCD) and major depressive disorder (MDD). Other indications under investigation include Tourette’s syndrome, anorexia nervosa and substance use disorders.

Aims: To review current studies on psychiatric indications for deep brain stimulation (DBS), with focus on OCD and MDD.

Method: A systematic search was carried out in MEDLINE, and the literature was searched to identify studies with DBS for psychiatric disorders. The identified studies were analysed based on patient characteristics, treatment results and adverse effects of DBS.

Results: A total of 52 papers met the inclusion criteria and described a total of 286 unique patients treated with DBS for psychiatric indications; 18 studies described 112 patients treated with DBS for OCD in six different anatomical targets, while nine studies presented 100 patients with DBS for MDD in five different targets.

Conclusion: DBS may show promise for treatment-resistant OCD and MDD but the results are limited by small sample size and insufficient randomized controlled data. Deep brain stimulation for OCD has received United States Food and Drug Administration approval. Other psychiatric indications are currently of a purely experimental nature.     

Content and correlates of checking related to symptoms of obsessive compulsive disorder and generalized anxiety disorder

In addition to the central role of compulsive behaviors in obsessive compulsive disorder (OCD), recent data have documented the presence of compulsive behaviors in individuals with generalized anxiety disorder (GAD). However, there is a lack of information about potential similarities and differences with regard to the quality, or content, of checking associated with worry and obsessions. The two studies presented herein are an initial step towards gathering this information. Findings of Study 1, from a large unselected undergraduate sample, showed that symptoms of OCD and GAD were both significantly associated with checking behaviors. However, while OCD symptoms were associated with checking related to both objects and interpersonal situations, GAD symptoms were only significantly associated with interpersonal checking. Findings of Study 2, using a separate sample, suggest links between interpersonal checking and features characteristic of GAD, namely emotion regulation difficulties, and between object checking and a cognitive feature of OCD, namely thought-action fusion. In summary, the current studies add to a growing body of literature suggesting that checking may be important in numerous forms of psychopathology, while also suggesting that the nature and function of checking may differ for various symptom profiles.     

阿立哌唑作为增效剂治疗强迫症的随机对照研究

目的探讨小剂量阿立哌唑作为增效剂治疗强迫症的疗效及安全性。方法 64例强迫症患者在帕罗西汀治疗的基础上,双盲、随机分为合用组[帕罗西汀合并阿立哌唑,阿立哌唑平均剂量（标准差）为7.9（1.3）mg/d]及对照组（帕罗西汀合并维生素C）,治疗8周。于治疗前及治疗后分别采用Yale-Brow强迫量表、治疗时出现的症状量表（TESS）评定药物疗效及不良反应。结果治疗前合用组和对照组帕罗西汀的平均剂量（标准差）分别为30.2（5.1）mg/d、29.6（6.1）mg/d,差异无统计学意义（t=0.86,P=0.291）;合用组和对照组Y-BOCS评分的均分（标准差）分别为25.0（2.4）、25.1（2.6）,差异无统计学意义（t=0.89,P=0.379）,治疗后两组的评分分别为17.9（3.3）、23.0（2.5）,差异有统计学意义（t=15.89,P〈0.001）。治疗后两组TESS评分无统计学差异。结论小剂量阿立哌唑可作为增效剂治疗强迫症,8周治疗后未见严重不良反应。     

强迫症患者治疗前后心率变异性的频谱分析

目的 观察强迫症患者治疗前后心率变异性的改变.方法 符合CCMD-3强迫症诊断标准的68例患者口服马来酸氟伏沙明治疗,治疗前后进行心率变异性检查.结果 强迫症组治疗前的心率变异性总功率(TP)、高频功率(HF)指标均低于正常对照组,差异有统计学意义(P＜0.01),低频功率/高频功率强迫症组治疗前高于正常对照组,差异具...     

脑深部电刺激在难治性强迫症治疗中的研究进展

强迫症是一组以强迫思维和(或)强迫行为为主要表现的精神疾病,目前临床上的一线治疗方案为5-羟色胺再摄取抑制剂和认知行为治疗。但仍有约40%~60%患者对一线治疗反应不佳或无效,称之为难治性强迫症。2009年美国及欧洲药监局批准的脑深部电刺激(deep brain stimulation,DBS)技术,作为一种神经调控的新型疗法能安全有效地改善难治性强迫症患者的症状。我们总结了现阶段对强迫症发病机制的了解,阐述了DBS应用于强迫症的历史和最新进展,并对其治疗机制、疗效、安全性、局限性及今后的发展方向等进行了综述。     

Objective sleep patterns and severity of symptoms in pediatric obsessive compulsive disorder: a pilot investigation

Sleep disturbances are common among youth with anxiety disorders, yet objective assessments of sleep in children with obsessive compulsive disorder (OCD) have been the focus of scant research. We therefore compared a small group of non-medicated, non-depressed children with primary OCD (ages 7-11 years) to matched healthy controls using home-based actigraphy during a 7-day prospective assessment. Validated parent and child sleep measures also were collected, and associations among objective sleep variables and severity of obsessions and compulsions were examined. We found significantly fragmented sleep patterns in the OCD group compared to controls including reduced total sleep time (TST) and longer wake periods after sleep onset. Severity of compulsions showed a significant negative correlation with TST. These preliminary findings indicate the presence of sleep abnormalities in pre-pubescent OCD patients with potential implications for future examinations of early developmental processes and features of the disorder.     

Tourette syndrome deep brain stimulation: A review and updated recommendations

Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25‐year‐old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post‐DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients. © 2014 International Parkinson and Movement Disorder Society     

The pedunculopontine nucleus as an additional target for deep brain stimulation

The pedunculopontine nucleus has been suggested as a target for DBS. In this paper we propose a single compartment computational model for a PPN Type I cell and compare its dynamic behavior with experimental data. The model shows bursts after a period of hyperpolarization and spontaneous firing at 8 Hz. Bifurcation analysis of the single PPN cell shows bistability of fast and slow spiking solutions for a range of applied currents. A network model for STN, GPe and GPi produces basal ganglia output that is used as input for the PPN cell. The conductances for projections from the STN and the GPi to the PPN are determined from experimental data. The resulting behavior of the PPN cell is studied under normal and Parkinsonian conditions of the basal ganglia network. The effect of high frequency stimulation of the STN is considered as well as the effect of combined high frequency stimulation of the STN and the PPN at various frequencies. The relay properties of the PPN cell demonstrate that the combined high frequency stimulation of STN and low frequency (10 Hz, 25 Hz, 40 Hz) stimulation of PPN hardly improves the effect of exclusive STN stimulation. Moreover, PPN-DBS at low stimulation amplitude has a better effect than at higher stimulation amplitude. The effect of PPN output on the basal ganglia is investigated, in particular the effect of STN-DBS and/or PPN-DBS on the pathological firing pattern of STN and GPe cells. PPN-DBS eliminates the pathological firing pattern of STN and GPe cells, whereas STN-DBS and combined STN-DBS and PPN-DBS eliminate the pathological firing pattern only from STN cells.     

The role of central oxytocin in obsessive compulsive disorder and related normal behavior

Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the CNS as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. Obsessive Compulsive Disorder (OCD) includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with OT. Anecdotal data and a recently completed cerebrospinal fluid (CSF) study provide evidence that some forms of OCD are related to OT dysfunction. Based on these findings, we hypothesize: 1) that some forms of OCD are at the extreme end of a range of normal behaviors that are mediated by OT and related systems; and that 2) some normal cognitive, affiliative, and sexual behaviors contain elements that are similar to features of OCD. Alternative hypotheses are considered, and a series of predictions are presented concerning the relationship between central OT and the onset, course, treatment response, and response to challenge procedures seen in this form of OCD.     

Impulse control disorders in adults with obsessive compulsive disorder

Little is known about impulse control disorders (ICDs) in individuals with obsessive compulsive disorder (OCD). Although studies have examined ICD comorbidity in OCD, no previous studies have examined clinical correlates of ICD comorbidity in a large sample of individuals with a primary diagnosis of OCD. We examined rates and clinical correlates of comorbid ICDs in 293 consecutive subjects with lifetime DSM-IV OCD (56.8% females; mean age=40.6+/-12.9 years). Comorbidity data were obtained with the Structured Clinical Interview for DSM-IV. ICDs were diagnosed with structured clinical interviews using DSM-IV criteria. OCD severity was assessed with the Yale-Brown Obsessive-Compulsive Scale. Quality of life and social/occupational functioning were examined using the Quality of Life Enjoyment and Satisfaction Questionnaire and the Social and Occupational Functioning Assessment Scale. All variables were compared in OCD subjects with and without lifetime and current ICDs. Forty-eight (16.4%) OCD subjects had a lifetime ICD, and 34 (11.6%) had a current ICD. Skin picking was the most common lifetime (10.4%) and current (7.8%) ICD, followed by nail biting with lifetime and current rates of 4.8% and 2.4%, respectively. OCD subjects with current ICDs had significantly worse OCD symptoms and poorer functioning and quality of life. These preliminary results suggest that there is a low prevalence of ICDs among individuals with OCD, although certain ICDs (skin picking) appear to be more common.     

Dysregulation in pediatric obsessive compulsive disorder

Although obsessive compulsive disorder (OCD) and common co-occurring conditions share deficits in self-regulatory abilities, there has been minimal examination of impaired self-regulation (dysregulation) in youth with OCD. This study examined the association of dysregulation with symptom severity, impairment, and treatment outcome in pediatric OCD. Clinicians assessed obsessive-compulsive severity, family accommodation and global severity in 144 youth with OCD. Youth completed self-report severity ratings of anxiety and depressive symptoms. Parents completed the Child Behavior Checklist (CBCL), and both children and parents completed parallel ratings of obsessive-compulsive impairment. Ninety-seven youth received cognitive behavioral therapy (CBT) and were re-assessed after treatment. Dysregulation was assessed using the CBCL-Dysregulation Profile. Before treatment, dysregulated youth exhibited greater obsessive-compulsive symptom severity, depressive mood, family accommodation, and impairment than non-dysregulated youth. The magnitude of dysregulation directly predicted child-rated impairment, parent-rated impairment, and family accommodation, beyond obsessive-compulsive severity. The magnitude of pretreatment dysregulation predicted treatment discontinuation but not treatment response. Obsessive-compulsive symptom severity and dysregulation level significantly decreased after CBT. Dysregulated youth with OCD presented as more clinically severe than their non-dysregulated counterparts, and may require more individualized interventions to reduce dysregulated behavior to prevent CBT attrition. For treatment completers, CBT was associated with a decrease in dysregulation level.     

Technology supported mindfulness for obsessive compulsive disorder: The role of obsessive beliefs

The current study examined the association of OCD symptoms and OCD belief domains, for individuals engaged in Technology Supported Mindfulness training (TSM) using an EEG-based biofeedback device (called “Muse”) that permits individuals to engage in home based mindfulness meditation practices. In this randomized controlled study, treatment-seeking participants with a principal DSM-5 diagnosis of OCD (N = 71) were randomly assigned to eight weeks of: 1) a meditation program involving daily use of the “Muse” device, or 2) wait list control. At weeks 1, 4, and 8, participants completed self-report measures of OCD symptoms (YBOCS: Yale-Brown Obsessive Compulsive Scale) and OCD beliefs (OBQ; OCCWG, 2005). Latent Difference Score (LDS) models indicated that there was no significant longitudinal relationship between OBQ “Responsibility/Threat” (OBQ R/T) scores and OCD symptoms. The analysis of OBQ “Perfectionism/Certainty” (OBQ P/C) and OCD symptoms demonstrated a significant reciprocal relationship between these two variables, in which OCD symptoms predicted subsequent increases in OBQ P/C and vice versa. The analysis of OBQ “Importance/Control of Thoughts” (OBQ I/C) and OCD symptoms demonstrated a significant reciprocal relationship between these two variables, in which OCD symptoms predicted subsequent increases in OBQ I/C and vice versa. The analysis of OBQ domains and EEG derived attentional changes demonstrated a significant association between OBQ P/C and Alpha band frequencies. These results clarify the association of OBQ belief domains, OCD symptom change and EEG derived indicators of attention during TSM.     

Neurological soft signs in obsessive compulsive disorder with good and poor insight

Objective

Obsessive compulsive disorder (OCD) is a clinically heterogeneous disorder; OCD with poor insight has been suggested to be a specific clinical subtype. Neurological soft signs (NSSs) may be helpful to identify the specific subtypes of OCD patients.

Methods

In the present study, we aimed to compare OCD patients with poor insight with OCD patients having good insight, and healthy individuals. Sixty-four OCD patients (38 with good insight and 26 with poor insight), and 32 healthy subjects were enrolled in the present study. The Overvalued Ideas Scale (OVIS) was used to determine OCD patients with poor insight. NSSs were assessed by using the Neurological Evaluation Scale (NES).

Results

Two OCD groups had significantly higher total NES scores compared to controls (p = .000). Compared to healthy controls, OCD patients with poor insight performed significantly worse on all NES subscales, and they had significantly more NSSs on motor coordination, and sensory integration subscales compared to the OCD with good insight group.

Conclusion

Our results suggested that OCD patients with poor insight exhibit more extensive neurodevelopmental impairments compared to OCD patients with good insight.