Wayne K. Goodman

A Preliminary Study of D-Cycloserine Augmentation of Cognitive-Behavioral Therapy in Pediatric Obsessive-Compulsive Disorder

BACKGROUND Research on the neural circuitry underlying fear extinction has led to the examination of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, as a method to enhance exposure therapy outcome. Preliminary results have supported the use of DCS to augment exposure therapy in adult anxiety disorders; however, no data have been reported in any childhood anxiety disorder. Thus, we sought to preliminarily examine whether weight-adjusted DCS doses (25 or 50 mg) enhanced the overall efficacy of cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD). METHOD Participants were 30 youth (aged 8-17) with a primary diagnosis of OCD. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining CBT + DCS versus CBT + Placebo (15 youth per group). All patients received seven exposure and response prevention sessions paired with DCS or placebo taken 1 hour before sessions. RESULTS Although not significantly different, compared with the CBT + Placebo group, youth in the CBT + DCS arm showed small-to-moderate treatment effects (d = .31-.47 on primary outcomes). No adverse events were recorded. CONCLUSIONS These results complement findings in adult OCD and non-OCD anxiety disorders and provide initial support for a more extensive study of DCS augmentation of CBT among youth with OCD.

Quality of life in children and adolescents with obsessive-compulsive disorder: base rates, parent–child agreement, and clinical correlates

The presence of obsessive-compulsive disorder (OCD) has been linked to decreased quality of life (QoL) among adults, yet little is known about the impact of OCD on QoL in pediatric patients. Sixty-two youth with OCD and their parent(s) were administered the Children’s Yale-Brown Obsessive Compulsive Scale following a clinical interview. Children completed the Pediatric Quality of Life Inventory and parents completed the Pediatric Quality of Life Parent Proxy Inventory and Child Behavior Checklist. QoL scores for OCD patients were significantly lower than for healthy controls, but similar to QoL in a general psychiatric sample on the majority of domains. Parent–child agreement on QoL was moderate to strong across age groups. Results indicate that, in youth with OCD, QoL is reduced relative to healthy controls, related to OCD symptom severity per parent-report, and are strongly predicted by the presence of comorbid externalizing and internalizing symptoms.

What's in a "smile?" intra-operative observations of contralateral smiles induced by deep brain stimulation

Abstract Objective: To descirbe smiling and euphoria induced by deep brain stimulation (DBS). Background and Significance: The brain systems inducing emotional experiences and displays are not entirely known, but the ventral striatum including the nucleus accumbens have been posited to play a critical role in mediating emotions with positive valence. DBS has been successfully employed for the treatment of movement disorders, and most recently obsessive compulsive disorder (OCD). The purpose of this report is to describe the emotional changes associated with stimulation of the ventral striatum. Methods: A single patient with intractable OCD had electrode arrays placed in the right and left anterior limbs of the internal capsule and region of the nucleus accumbens. Changes in facial movement during stimulation were quantified by video recording. Ten video segments, time locked to the onset of stimulation, were digitized and changes in pixel intensity that occurred over both sides of the lower face, on a frame by frame basis, following stimulation onset were computed. These summed changes in pixel intensity represented the dependent variable of “entropy” and directly corresponded to changes in light reflectance that occur during facial movement. Results: During stimulation on both the right and left side, the patient consistently developed a half smile on the side of the face contralateral to the stimulating electrode, and also became euphoric. The effect ceased when DBS was discontinued. Conclusions: DBS in the region of the nucleus accumbens produced smile and euphoria suggesting that alterations in the ventral striatum may result in emotional experience and displays. We hypothesize the existence of a limbic-motor network responsible for such changes. This observation suggests that DBS may be useful as a therapy for mood disorders.

Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

OBJECTIVE To explore associated clinical factors in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). STUDY DESIGN Children with tics, obsessive-compulsive disorder, or both (n=109) were examined with personal and family history, diagnostic interview, physical examination, medical record review, and measurement of baseline levels of streptococcal antibodies. RESULTS Significant group differences were found on several variables, such that children in whom PANDAS (versus without PANDAS) were more likely to have had dramatic onset, definite remissions, remission of neuropsychiatric symptoms during antibiotic therapy, a history of tonsillectomies/adenoidectomies, evidence of group A streptococcal infection, and clumsiness. CONCLUSION The identification of clinical features associated with PANDAS should assist in delineating risks for this subtype of obsessive-compulsive disorder/tics.

Development and Psychometric Evaluation of the Yale-Brown Obsessive-Compulsive Scale--Second Edition.

The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; Goodman, Price, Rasmussen, Mazure, Delgado, et al., 1989) is acknowledged as the gold standard measure of obsessive-compulsive disorder (OCD) symptom severity. A number of areas where the Y-BOCS may benefit from revision have emerged in past psychometric studies of the Severity Scale and Symptom Checklist. Therefore, we created the Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II) by revising the Severity Scale item content and scoring framework, integrating avoidance into the scoring of Severity Scale items, and modifying the Symptom Checklist content and format. One hundred thirty treatment-seeking adults with OCD completed a battery of measures assessing OCD symptom severity and typology and depressive and anxious symptomology. Interrater and test-retest reliability were assessed on a subsample of participants. The Y-BOCS-II showed strong internal consistency for the Symptom Checklist (Kuder-Richardson-20 = .91) and Severity Scale (alpha = .89). Test-retest and interrater reliabilities were both high (intraclass correlations > .85). Confirmatory factor analyses did not show adequate fit with previous models of the Y-BOCS. Exploratory factor analysis revealed a two-factor solution generally consistent with the Obsession and Compulsion Severity subscales. Construct validity was supported by strong correlations with clinician-rated measures of OCD symptom severity and moderate correlations with measures of worry and depressive symptoms. Taken together, the Y-BOCS-II has excellent psychometric properties in assessing the presence and severity of obsessive-compulsive symptoms. Although the Y-BOCS remains a reliable and valid measure, the Y-BOCS-II may provide an alternative method of assessing symptom presence and severity.

A Trial of Scheduled Deep Brain Stimulation for Tourette Syndrome Moving Away From Continuous Deep Brain Stimulation Paradigms

OBJECTIVE To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. DESIGN We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. SETTING A university movement disorders center. PATIENTS Five patients with implanted DBS. MAIN OUTCOME MEASURE A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. CONCLUSIONS This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01329198.

Deep Brain Stimulation for Intractable Psychiatric Disorders

Deep brain stimulation (DBS) has virtually replaced ablative neurosurgery for use in medication-refractory movement disorders. DBS is now being studied in severe psychiatric conditions, such as treatment-resistant depression (TRD) and intractable obsessive-compulsive disorder (OCD). Effects of DBS have been reported in ∼100 cases of OCD and ∼50 cases of TRD for seven (five common) anatomic targets. Although these published reports differ with respect to study design and methodology, the overall response rate appears to exceed 50% in OCD for some DBS targets. In TRD, >50% of patients responded during acute and long-term bilateral electrical stimulation in a different target. DBS was generally well tolerated in both OCD and TRD, but some unique, target- and stimulation-specific adverse effects were observed (e.g., hypomania). Further research is needed to test the efficacy and safety of DBS in psychiatric disorders, compare targets, and identify predictors of response.

Children’s Florida Obsessive Compulsive Inventory: Psychometric Properties and Feasibility of a Self-Report Measure of Obsessive–Compulsive Symptoms in Youth

This report describes the development and psychometric properties of the Children’s Florida Obsessive Compulsive Inventory (C-FOCI). Designed specifically as a brief measure for assessing obsessive–compulsive symptoms, the C-FOCI was created for use in both clinical and community settings. Study 1 included 82 children and adolescents diagnosed with primary Obsessive–Compulsive Disorder, and their parents. The Children’s Yale-Brown Obsessive–Compulsive Scale (CY-BOCS) was administered to assess symptom severity. Thereafter, parents completed the Child Obsessive–Compulsive Impact Scale—Parent Version and Child Behavior Checklist, and youth completed the C-FOCI, Child Obsessive–Compulsive Impact Scale—Child Version, Multidimensional Anxiety Scale for Children, and Children’s Depression Inventory—Short Form. A subgroup of 21 individuals was retested with the C-FOCI after completing 14 sessions of intensive cognitive-behavioral therapy. Construct validity of the C-FOCI was supported vis-à-vis evidence of treatment sensitivity, and moderate relations with clinician-rated symptom severity, the CY-BOCS Symptom Checklist, child- and parent-rated functional impairment, child-rated anxiety, and parent-rated internalizing symptoms. Discriminant validity was evidenced by weak relationships with parent-reports of externalizing symptoms. For Study 2, 191 non-clinical adolescents completed the C-FOCI to assess the feasibility of internet administration. Overall, internal consistency was acceptable for the C-FOCI Symptom Checklist and Severity Scale, and respondents were able to complete the measure with little difficulty. Taken together, the findings of Studies 1 and 2 provide initial support for the reliability and validity of the C-FOCI for the assessment of pediatric obsessive–compulsive symptoms.

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.

A Case of Mania following Deep Brain Stimulation for Obsessive Compulsive Disorder

Deep brain stimulation (DBS) of the basal ganglia is an effective treatment for select movement disorders, including Parkinson’s disease, essential tremor and dystonia. Based on these successes, DBS has been explored as an experimental treatment for medication-resistant neuropsychiatric disease. During a multiyear experience employing DBS to treat patients for obsessive compulsive disorder (OCD) we encountered several unanticipated stimulation-induced psychiatric side effects. We present a case of a young woman treated for OCD with DBS of the anterior limb of the internal capsule and nucleus accumbens region, who subsequently manifested a manic episode. We aim to discuss the case details, treatment and potential neuroanatomical underpinnings of this response.