Jamie A. Micco

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.

High risk studies and developmental antecedents of anxiety disorders

The past two decades have witnessed significant growth in our understanding of the developmental antecedents of anxiety disorders. In this article, we review studies of offspring at risk for anxiety disorders, longitudinal studies of the course of anxiety disorders in clinical, epidemiologic, and at‐risk samples, studies of hypothesized temperamental risk factors for anxiety, and give a brief overview of the literature on environmental risk factors. Clear developmental antecedents to anxiety disorders identified include (1) childhood anxiety disorders [in particular, separation anxiety and overanxious disorder/general anxiety disorder (GAD)], (2) behavioral inhibition which predicts later social phobia, (3) anxiety sensitivity which predicts later panic disorder, and (4) negative affectivity, which predicts a spectrum of psychopathology including anxiety disorders. Further prospective studies are needed to examine the roles of environmental factors such as parenting practices, peer influences, stressful life events, and perinatal stressors. Future studies could benefit from (1) beginning earlier in development and following individuals into adulthood, (2) assessing the overlap between multiple temperamental constructs, (3) greater use of observational measures of temperament and of parent–child and peer interactions, (4) greater attention to parental psychopathology which may confound associations noted, (5) exploration of other features of anxiety disorders (neurofunctional correlates, cognitive features, other aspects of emotional regulation) as potential precursors, and (6) intervention studies exploring whether modifying developmental antecedents can alter the course of anxiety disorders.

Anxiety and depressive disorders in offspring at high risk for anxiety: A meta-analysis

This paper presents a meta-analysis of studies examining prevalence of psychopathology among offspring of anxiety-disordered parents, with the purpose of determining overall risk among these offspring for developing anxiety and depressive disorders. Pooled odds ratios for these disorders among high-risk offspring, compared to offspring of psychiatric and non-psychiatric controls, were calculated. Sixteen papers (including three follow-up studies) were identified, encompassing 1892 offspring (ages 4-25 years). Results revealed that: (1) offspring of parents with anxiety disorders have greater risk for anxiety and depressive disorders than offspring of non-psychiatric controls (ORs=3.91 and 2.67, respectively) and greater risk for anxiety disorders than offspring of psychiatric controls (OR=1.84); (2) offspring of anxious parents have significantly greater odds of having each type of anxiety disorder and MDD compared to offspring of non-psychiatric controls (ORs range from 1.96 to 8.69); and (3) offspring of parents with anxiety only, anxiety plus MDD, and MDD only have similar odds of having anxiety and depressive disorders but significantly higher odds than offspring of parents without disorder. Results suggest that parental anxiety disorders confer significant risk for anxiety and depression in offspring. Additional studies are needed to examine whether there are differences among specific parental anxiety disorders.

Executive functioning in offspring at risk for depression and anxiety

Background: Executive functioning deficits (EFDs) have been found in adults with major depression and some anxiety disorders, yet it is unknown whether these deficits predate onset of disorder, or whether they reflect acute symptoms. Studies of at‐risk offspring can shed light on this question by examining whether EFDs characterize children at high risk for depression and anxiety who are not yet symptomatic. Methods: This study examined neuropsychological functioning in a sample of 147 children, ages 6–17 years (M age=9.16, SD=1.82), of parents with major depression (MDD) and/or panic disorder (PD) and of controls with neither disorder. Children were assessed via structured diagnostic interviews and neuropsychological measures. Results: Although parental MDD and PD were not associated with neuropsychological impairments, presence of current offspring MDD was associated with poorer performance on several executive functioning and processing speed measures. Children with current generalized anxiety showed poorer verbal memory, whereas children with social phobia had more omissions on a continuous performance task. Conclusions: Findings suggest that EFDs do not serve as trait markers for developing anxiety or depression but appear to be symptomatic of current disorder. Depression and Anxiety, 2009.

Child Behavior Checklist Clinical Scales Discriminate Referred Youth With Autism Spectrum Disorder: A Preliminary Study

Objective: To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating referred children with autism spectrum disorders (ASDs) (autistic disorder, Aspergers disorder, and pervasive developmental disorder not otherwise specified) from psychiatrically referred children without ASDs. Method: Comparisons were made between children with ASDs (n = 65) with intelligence quotient >70 and children without ASDs (N = 83) on the clinical scales of the Child Behavior Checklist. Stepwise logistic regression was used to identify those scales that best predicted ASDs when compared with the non-ASD comparison group. Receiver operating characteristic curves examined the ability of the significant predictor T-scores to identify ASDs versus the non-ASD subjects. Results: Withdrawn, Social Problems, and Thought Problems T-scores were the best independent predictors of ASD status. The Withdrawn + Social + Thought Problems T-scores yielded an area under the curve of 0.86, indicating an 86% chance that a randomly selected sample of ASD subject will have abnormal scores on these scales than a randomly selected sample of non-ASD subjects. Conclusion: These findings suggest that a new Child Behavior Checklist-ASD profile consisting of the Child Behavior Checklist-Withdrawn, Social, and Thought Problems scales could serve as a rapid and cost-effective screening instrument to help identify cases likely to meet clinical criteria for ASDs in the clinical setting.

Clinical Outcomes of Laboratory-Observed Preschool Behavioral Disinhibition at Five-Year Follow-up

BACKGROUND Behavioral disinhibition refers to a temperamental tendency to exhibit boldness, approach, and spontaneity in unfamiliar situations. We previously found it to be associated with childhood disruptive behavior and mood disorders, as well as with parental bipolar disorder. In the present study, our objective was to examine the diagnostic outcome in middle childhood of behavioral disinhibition assessed at preschool age among offspring at risk for anxiety and mood disorders. METHODS The sample consisted of 284 children, including offspring of parents with panic disorder or major depression and comparison offspring of parents without these disorders, who had been assessed with laboratory observations of temperament at ages 21 months to 6 years. We reassessed 215 of the children (77%) at 5-year follow-up (mean age 9.6 years) with structured diagnostic interviews. RESULTS Compared with noninhibited, nondisinhibited control subjects, behaviorally disinhibited children had higher lifetime rates of comorbid mood plus disruptive behavior disorders and higher current rates of any disruptive behavior disorder and of oppositional defiant disorder. CONCLUSIONS Behavioral disinhibition appears to be a temperamental antecedent of disruptive behavior disorders and their comorbidity with mood disorders in middle childhood, which may be targeted for preventive intervention.

Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth

OBJECTIVE To evaluate the impact of psychopharmacologic treatments on neuropsychological functioning in bipolar youth. METHOD Participants were 173 children (aged 6-17 years) with DSM-IV bipolar disorder. Participants were comprehensively assessed using structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and neuropsychological measures (eg, subtests of the Wechsler Intelligence Scale for Children-III and Wechsler Adult Intelligence Scale-III) during the years 2001-2006. Comparisons were made in neuropsychological functioning between medicated and unmedicated youth with bipolar disorder. RESULTS Children who were treated with mood stabilizers performed significantly (P < .05) more poorly than untreated children on measures of processing speed and working memory. Treatment with other classes of medication, including second-generation antipsychotics, was not significantly associated with neuropsychological impairments. CONCLUSIONS Treatment with mood stabilizers may be associated with specific neuropsychological impairments. Cognitive side effects may need to be considered in selecting particular psychopharmacologic treatments for children with bipolar disorder.

Applying Cognitive-Behavioral Therapy for Anxiety to the Younger Child

Cognitive-behavioral therapy (CBT) protocols for anxiety disorders have been shown to have efficacy with older children and adolescents; however, only recently have investigators begun to adapt and pilot such interventions for younger children. This article reviews data suggesting that even very young children can benefit from CBT for anxiety, discusses some of the necessary developmental adaptations when working with children of preschool and early elementary school age, and reviews studies that have implemented CBT for anxiety disorders with youngsters in this age range. The authors conclude with recommendations for future directions for research in this area.

Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

IMPORTANCE Cognitive behavior therapy (CBT) among youth with obsessive-compulsive disorder (OCD) is effective, but many patients remain symptomatic after intervention. d-cycloserine, a partial agonist at the N-methyl-d-aspartate receptor in the amygdala, has been associated with enhanced CBT outcome for OCD among adults but requires evaluation among youth. OBJECTIVES To examine the relative efficacy of weight-adjusted d-cycloserine (25 or 50 mg) vs placebo augmentation of CBT for youth with OCD and to assess if concomitant antidepressant medication moderated effects. DESIGN, SETTING, AND PARTICIPANTS In a placebo-controlled randomized clinical trial, 142 youths (age range, 7-17 years) enrolled between June 1, 2011, and January 30, 2015, at 2 academic health science centers (University of South Florida and Massachusetts General Hospital) with a primary diagnosis of OCD were randomized in a double-blind fashion to d-cycloserine plus CBT or placebo plus CBT. Intent-to-treat analysis was performed. INTERVENTIONS Patients were randomly assigned in a 1:1 ratio to either 10 sessions of d-cycloserine plus CBT or placebo plus CBT. d-cycloserine (25 or 50 mg) or placebo was taken 1 hour before sessions 4 through 10. MAIN OUTCOMES AND MEASURES Childrens Yale-Brown Obsessive Compulsive Scale at randomization, biweekly, midtreatment, and posttreatment. Secondary outcomes included the Clinical Global Impressions-Severity or Clinical Global Impressions-Improvement, remission status, Childrens Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Childrens Obsessive-Compulsive Impact Scale-Parent Version. RESULTS The study cohort comprised 142 participants. Their mean (SD) age was 12.7 (2.9) years, and 53.5% (76 of 142) were female. A mixed-effects model using all available data indicated significant declines in the Childrens Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions-Severity. No significant interaction between treatment group and changes in the Childrens Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity indicated that the d-cycloserine plus CBT group and the placebo plus CBT group declined at similar rates per assessment point on the Childrens Yale-Brown Obsessive Compulsive Scale total score (estimate, -2.31, 95% CI, -2.79 to -1.83 and estimate, -2.03, 95% CI, -2.47 to -1.58, respectively) and Clinical Global Impressions-Severity (estimate, -0.29, 95% CI, -0.35 to -0.22 and estimate, -0.23, 95% CI, -0.29 to -0.17, respectively). No group differences in secondary outcomes were present. Antidepressant medication use at baseline did not moderate changes for either group. CONCLUSIONS AND RELEVANCE d-cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD. Other augmentation approaches should be examined to enhance outcome. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00864123.

Cognitive Behavioral Therapy with Children and Adolescents

Cognitive behavioral therapy (CBT) has demonstrated efficacy in treating a number of disorders in children and adolescents. This chapter provides a detailed description of the CBT approaches and techniques that are most commonly used with youth, including psychoeducation, relaxation training, cognitive restructuring, problem solving, behavioral exposure, and organizational skills training. In addition, it reviews assessment tools, strategies and instruments for use with children and adolescents, and discusses the role of parents in treatment. Throughout, developmental adaptions of CBT techniques and their use with children across a broad age range are emphasized. The empirical support for the use of CBT with youth is briefly reviewed, and a case example is provided to illustrate relevant clinical applications and common challenges.