Tanya K. Murphy

Family Accommodation in Pediatric Obsessive–Compulsive Disorder

Despite the importance of the family in the treatment of pediatric obsessive–compulsive disorder (OCD), relatively little empirical attention has been directed to family accommodation of symptoms. This study examined the relations among family accommodation, OCD symptom severity, functional impairment, and internalizing and externalizing behavior problems in a sample of 57 clinic-referred youth 7 to 17 years old (M = 12.99 ± 2.54) with OCD. Family accommodation was a frequent event across families. Family accommodation was positively related to symptom severity, parent-rated functional impairment (but not child-rated impairment), and externalizing and internalizing behavior problems. Family accommodation mediated the relation between symptom severity and parent-rated functional impairment.

Psychometric evaluation of the Children's Yale–Brown Obsessive-Compulsive Scale

This study evaluated the psychometric properties of the Childrens Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). A total of 61 children and adolescents, aged 4-18 years, who were diagnosed with obsessive-compulsive disorder (OCD) participated. Thirty-seven of these children also participated in a second CY-BOCS administration by the same rater an average of 41 days later. Good internal consistency and test-retest reliability were found for the CY-BOCS Obsession and Compulsion Severity Scores and the Total Score. CY-BOCS scores demonstrated strong correlations with clinician-rated measures of impairment, obsessions, and compulsions. In addition, CY-BOCS scores were moderately related to measures of depression, aggressive behavior, and symptoms of attention deficit hyperactivity disorder, but were not significantly related to clinician ratings of tics or self-reports of general anxiety. Findings suggest that the CY-BOCS is a reliable and valid instrument for the assessment of childhood obsessions and compulsions.

Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders

Recent reports of autoantibodies that bind to neuronal surface receptors or synaptic proteins have defined treatable forms of autoimmune encephalitis. Despite these developments, many cases of encephalitis remain unexplained. We have previously described a basal ganglia encephalitis with dominant movement and psychiatric disease, and proposed an autoimmune aetiology. Given the role of dopamine and dopamine receptors in the control of movement and behaviour, we hypothesized that patients with basal ganglia encephalitis and other putative autoimmune basal ganglia disorders harboured serum autoantibodies against important dopamine surface proteins. Basal ganglia encephalitis sera immunolabelled live surface cultured neurons that have high expression of dopamine surface proteins. To detect autoantibodies, we performed flow cytometry cell-based assays using human embryonic kidney cells to express surface antigens. Twelve of 17 children (aged 0.4-15 years, nine males) with basal ganglia encephalitis had elevated immunoglobulin G to extracellular dopamine-2 receptor, compared with 0/67 controls. Immunofluorescence on wild-type mouse brain showed that basal ganglia encephalitis sera immunolabelled microtubule-associated protein 2-positive neurons in striatum and also in cultured striatal neurons, whereas the immunolabelling was significantly decreased in dopamine-2 receptor knock-out brains. Immunocytochemistry confirmed that immunoreactivity localized to the surface of dopamine-2 receptor-transfected cells. Immunoabsorption of basal ganglia encephalitis sera on dopamine-2 receptor-transfected human embryonic kidney cells decreased immunolabelling of dopamine-2 receptor-transfected human embryonic kidney cells, neurons and wild-type mouse brain. Using a similar flow cytometry cell-based assay, we found no elevated immunoglobulin G binding to dopamine 1, 3 or 5 receptor, dopamine transporter or N-methyl-d-aspartate receptor. The 12 dopamine-2 receptor antibody-positive patients with encephalitis had movement disorders characterized by parkinsonism, dystonia and chorea. In addition, the patients had psychiatric disturbance with emotional lability, attention deficit and psychosis. Brain magnetic resonance imaging showed lesions localized to the basal ganglia in 50% of the patients. Elevated dopamine-2 receptor immunoglobulin G was also found in 10/30 patients with Sydenhams chorea, 0/22 patients with paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and 4/44 patients with Tourettes syndrome. No dopamine-1 receptor immunoglobulin G was detected in any disease or control groups. We conclude that assessment of dopamine-2 receptor antibodies can help define autoimmune movement and psychiatric disorders.

Impact of Comorbidity on Cognitive-Behavioral Therapy Response in Pediatric Obsessive-Compulsive Disorder.

OBJECTIVE To examine the impact of psychiatric comorbidity on cognitive-behavioral therapy response in children and adolescents with obsessive-compulsive disorder. METHOD Ninety-six youths with obsessive-compulsive disorder (range 7-19 years) received 14 sessions of weekly or intensive family-based cognitive-behavioral therapy. Assessments were conducted before and after treatment. Primary outcomes included scores on the Childrens Yale-Brown Obsessive-Compulsive Scale, response rates, and remission status. RESULTS Seventy-four percent of participants met criteria for at least one comorbid diagnosis. In general, participants with one or more comorbid diagnoses had lower treatment response and remission rates relative to those without a comorbid diagnosis. The number of comorbid conditions was negatively related to outcome. The presence of attention-deficit/hyperactivity disorder and disruptive behavior disorders was related to lower treatment response rates, and the presence of disruptive behavior disorders and major depressive disorder were related to lower remission rates. CONCLUSIONS The presence of a comorbid disorder, particularly disruptive behavior, major depressive, and attention-deficit/hyperactivity disorders, has a negative impact on treatment response. Assessing for psychiatric disorders before treatment entry and treating these comorbid conditions before or during cognitive-behavioral therapy may improve final outcome. Comorbid anxiety or tic disorders do not seem to negatively affect response.

D-cycloserine does not enhance exposure-response prevention therapy in obsessive-compulsive disorder

Obsessive–compulsive disorder is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for obsessive–compulsive disorder are exposure and response prevention therapy and the serotonin reuptake inhibitors. Many patients do not experience complete symptom resolution with either modality and require augmentation approaches. Recent animal and clinical data suggest that D-cycloserine, a partial agonist that acts at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate receptor complex, may enhance extinction learning that occurs in exposure-based psychotherapies. Given this, this study examined if D-cycloserine (250 mg) enhances the overall efficacy and rate of change of exposure and response prevention therapy for adult obsessive–compulsive disorder. Participants were 24 adults meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for obsessive–compulsive disorder. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining exposure and response prevention therapy+D-cycloserine versus exposure and response prevention therapy+placebo. All patients received 12 weekly sessions of exposure and response prevention treatment. The first session involved building a ritual hierarchy and providing psychoeducation about obsessive–compulsive disorder. The second session involved a practice exposure. Sessions 3–12 involved exposure and response prevention exercises. D-cycloserine or placebo (250 mg) was taken 4 h before every session. No significant group differences were found across outcome variables. The rate of improvement did not differ between groups. The present results fail to support the use of D-cycloserine with exposure and response prevention therapy for adult obsessive–compulsive disorder. As this study is the first to explore this question and a number of methodological issues must be considered when interpreting the findings, the conclusions that may be drawn from our results are limited.

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.

The Effect of Cognitive-Behavioral Therapy Versus Treatment as Usual for Anxiety in Children With Autism Spectrum Disorders: A Randomized, Controlled Trial

OBJECTIVE To examine the efficacy of a modular cognitive-behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among children with high-functioning autism spectrum disorders (ASD) and clinically significant anxiety. METHOD A total of 45 children (7-11 years of age) with high-functioning ASD and clinically significant anxiety were randomized to receive 16 sessions of weekly CBT or TAU for an equivalent duration. After screening, assessments were conducted at baseline, post-treatment, and 3-month follow-up. Raters were blind to treatment condition. RESULTS Youth receiving CBT showed substantial improvement relative to TAU on primary anxiety outcomes. Of 24 children randomized to the CBT arm, 18 (75%) were treatment responders, versus only 3 of 21 children (14%) in the TAU arm. Gains were generally maintained at 3-month follow-up for CBT responders. CONCLUSIONS Relative to usual care, CBT adapted for anxious youth with high-functioning ASD demonstrates large effects in reducing anxiety symptoms. This study contributes to the growing literature supporting adapted CBT approaches for treating anxiety in youth with ASD.

Reliability and validity of the yale global tic severity scale

To investigate the reliability and validity of the Yale Global Tic Severity Scale (YGTSS), 28 youth aged 6 to 17 years with Tourettes syndrome (TS) participated in the study. Data included clinician reports of tics and obsessive-compulsive disorder (OCD) severity, parent reports of tics, internalizing and externalizing problems, and child reports of depression and anxiety. All children participated in a 2nd YGTSS administration by the same rater 48 days later. Good internal consistency and stability were found for the YGTSS scores. YGTSS scores demonstrated strong correlations with parent-rated tic severity (r = .58-.68). YGTSS scores were not significantly related to measures of clinician ratings of OCD severity (r = .01-.15), parent ratings of externalizing and internalizing behavior (r = -.07-.20), and child ratings of depression (r = .02-.26) and anxiety (r = -.06 -.28). Findings suggest that the YGTSS is a reliable and valid instrument for the assessment of pediatric TS.

Quality of life in youth with Tourette's syndrome and chronic tic disorder.

This study sought to examine quality of life (QoL) in clinic-referred children and adolescents (n = 59, M age = 11.4±2.6 years) with a chronic tic disorder. The QoL scores for tic patients were lower than for healthy controls but higher than for the psychiatric sample on the majority of domains. Childrens self-reported QoL scores and a measure of tic severity were moderately and inversely correlated. Parent reports of their childs QoL were weakly related to tic severity. Correlations between parent and child ratings of QoL for children ages 8 to 11 years were generally higher than those for youth ages 12 to 17 years. Finally, externalizing behavior moderated the relations between tic severity and parent-rated QoL, such that tic severity was significantly associated with parent-rated QoL for children with below average externalizing symptoms but not for children 3with above average externalizing symptoms.

A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder

BACKGROUND One of the few combination approaches to the treatment of obsessive-compulsive disorder (OCD) with encouraging support is the addition of an antipsychotic to a serotonin reuptake inhibitor. METHODS The study consisted of a 6-week, placebo-controlled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject). RESULTS Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] according to Yale-Brown Obsessive Compulsive Scale scores with repeated-measures analysis of variance; however, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine. CONCLUSIONS These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial.