Philip C. Kendall - US grants

Anxiety disorders are prevalent in school-aged children and may lead to difficulties in academic and interpersonal functioning. The purpose of the present study is to develop and evaluate treatment approaches for anxious children. The proposed study is for 9-13 year-old children identified as overanxious, separation anxiety, or avoidant disorder. The research will compare a cognitive-behavioral treatment program with a waiting-list control. An ancillary purpose of the present proposal is to assess the cognitive features involved in child anxiety and to develop relevant cognitive assessment strategies. Children who are referred by mental health professionals to the Child and Adolescent Anxiety Disorders Clinic will be screened for inclusion using a structured diagnostic interview. Those children who are diagnosed anxiety disordered will be randomly assigned to one of the conditions. All children will receive 15 weekly 55 minute sessions. The focus of the cognitive- behavioral treatment will be on four major components: 1. recognizing anxious thoughts and somatic reactions to anxiety. 2. clarifying cognitions in anxiety provoking situations. 3. developing a plan to cope with the situation. 4. evaluating the performance and self-reinforcement as appropriate. Behavioral techniques such as modeling, role play, relaxation and contingent reinforcement will be used. The waiting-list control condition will be administered the same measures as the children at the beginning and the end of the treatment period to control for treatment expectancies and the transience of anxiety. Treatment effects will be analyzed through a repeated measures (treatment conditional) * (assessment periods) mixed factorial ANOVA. Since dependent measures are highly interrelated, MANOVA will be used for same-method measures. ANCOVA will be used in the event of pretreatment differences. The assessment battery consists of children's self-report measures (RCMAS, STAIC, FSSC-R, CDI), parent and teacher measures (CBCL), cognitive assessment (CASSQ), and behavioral observations in an interview situation. Other measures, such as the child's perception of the therapeutic relationship (CPTR), the therapist's report of the child's compliance with homework, and a rating of the child's parent's perception of the child's coping skills will be examined. Client characteristics, pretreatment variables, and process variables will be examined in relation to outcome. The same battery will be used at 1 year follow-up. The diagnosis of specific anxiety disorders will be used to examine differential responsiveness of these disorders to the treatments.

The purpose of the present study is to further develop and conduct a randomized clinical trial to evaluate a treatment approach for 9-13 yr-old anxiety-disordered children. It will compare a 16-week cognitive- behavioral (C-B) treatment with an 8-week wait-list control condition. C-B consists of skill building (8 wks) and exposure and rehearsal (8 wks). In addition to overall effects, the separate effects of the first and second segments of the treatment will be examined. The study will also assess cognitive features involved in childhood anxiety. Referred youth will be diagnosed via structured interviews. Subjects will be randomly assigned to one of the conditions, and to one of the therapists. Comorbidity will also be determined. Wait-list subjects will receive treatment after the wait period. All children will receive individual weekly, 60-minute sessions. C-B will focus on: 1. recognizing anxious thoughts and somatic reactions; 2. clarifying cognition in anxiety- provoking situations; 3. developing a coping plan; and 4. evaluating performance and self-reinforcement. Behavioral techniques such as modeling, role-play, exposure, relaxation, and reinforcement will be used. Subjects in the wait-list condition will be administered (pre-post wait period) the same measures as the treated children. Treated children will be assessed at pre-, mid-, and post-treatment, and at one-year follow-up. Treatment effects will be analyzed via 2 (conditions) X 2 (assessments) mixed factorial ANOVA. When dependent measures are highly interrelated, MANOVA will be used (ANCOVA if pretreatment differences). Assessments include children's self-reports, teacher measures, parent measures of their children and of themselves, and behavioral observations. Other measures (e.g., relationship, compliance, parental involvement), and client pretreatment characteristics (e.g., age) will be examined in relation to outcome. Specific anxiety disorders, as well as the presence of other disorders (comorbidity with depression will be used to examine differential responsiveness to treatment.

One hundred fifty (150) youth (9- 13 year-olds) diagnosed with a primary anxiety disorder will participate in a randomized clinical trial, with 50 cases randomly assigned to Individual Cognitive-Behavioral Therapy (ICBT), 50 cases to Family Cognitive-Behavioral Therapy (FCBT), and 50 cases to an education/support/attention (ESA) control condition. All conditions will be 16 sessions. ICBT and FCBT involve anxiety education, relaxation, relabeling of anxiety-related cognition, problem-solving, exposure, and rehearsal. The ESA condition provides participants with support and attention from a therapist and education about emotions and anxiety. The study will employ multimethod assessment including structured diagnostic interviews, child and parent self-reports, parent and teacher ratings of the child, behavioral observations, and family assessments. Measures will be gathered at pre- and post-treatment, and at one-year follow-up. To ensure that treatment-as-described was provided, treatment integrity will be assessed. Behavioral observations will be taken from videotapes, with two raters (.85 reliability; Kappa) for the child observational system and two for the family coding system. Treatment effects will be analyzed via 3 (conditions; between subjects) X 3 (assessments; within subjects) MANOVA and mixed factorial analysis of variance. Because several dependent measures may be highly interrelated (e.g., self-reports) multivariate analyses of variance will be used for same-method measures (e.g., self-reports). The study will examine maintenance via analyses of one-year follow-up data. The analyses will be conducted for both treatment completers and the intent-to-treat sample. Examinations of clinical significance, predictors of treatment outcome, and differential responsiveness to the two treatments will be conducted.

DESCRIPTION (Adapted from Applicant's Abstract): Adults with anxiety disorders often report onset during childhood. Treating youth with anxiety disorders may reduce the likelihood of future anxiety disorders and their sequelae. This study will evaluate (a) the long-term maintenance of treatment gains for treated anxiety-disordered youth and (b) changes in the sequelae of anxiety disorders. Ninety-four (94) youth who had been diagnosed with an anxiety disorder and who had completed treatment in a randomized clinical trial (reported in Kendall et al., 1997) will participate. Participants will have completed treatment 5 to 7 years prior (average 6-year follow-up) and will return for a diagnostic evaluation (structured interview of the child and of the parent about the child) and to complete multiple self-report measures. Diagnostic interviews and self-report measures will be administered to assess current anxiety levels, depressive symptoms, substance use, and other comorbid disorders. An assessment of the participants recall of treatment content and their life events since therapy will be gathered. MANOVA analyses, of the dependent variables, will be used to compare the published pre-treatment and post-treatment data to the long-term follow-up data gathered with this application. Pre-treatment characteristics of the participants, as well as participant recall of treatment content and life events since treatment, will be examined as potential predictors of diagnostic status and functioning at long-term follow-up. Partial correlation analyses and multiple regression analyses will be used. The present study will also examine, using structured diagnostic procedures, whether successfully treated anxiety-disordered youth, as compared to those whose prior treatment was not successful, evidence differences in the sequelae of anxiety disorders such as depressive symptoms and substance abuse. The present study will provide the longest follow-up data to date on treated, anxiety-disordered youth, and will provide the first examination of the disorder.

DESCRIPTION (provided by applicant): With point prevalence estimates ranging from 12 percent to 20 percent, anxiety disorders are among the most common conditions affecting children and adolescents. The three most commonly impairing childhood-onset anxiety disorders are separation anxiety disorder, social phobia and generalized anxiety disorder. As a group, these disorders routinely co-occur and cause clinically significant distress and impairment affecting school, social, and family functioning. Left untreated, these disorders leave children at risk for anxiety disorders, major depression and, in some cases, substance abuse extending into late adolescence and adulthood. Hence, effective treatments for childhood-onset anxiety disorders promise to alleviate and perhaps to prevent long-term morbidity and even mortality. In randomized controlled trials, we have shown that two monotherapies, cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitor (SSRI), fluvoxamine (FLV), are effective treatments for separation anxiety, social phobia, and generalized anxiety disorders in children and adolescents. Even though the monotherapies are effective a substantial number of patients remain symptomatic following treatment and, might have benefited from combined treatment. There are as yet no systematic, controlled studies comparing CBT and an SSRI, alone or in combination, against a control condition in the same patient population. This revised application proposes a four-year, six site, randomized controlled efficacy trial comparing cognitive-behavioral (CBT) and pharmacological treatment for youth ages 7 to 16 years with anxiety disorders. Phase 1 is a 12-week, random assignment acute efficacy study comparing CBT, FLV, their combination (n=90, each condition), and pill placebo control (n=48) in 318 (53/site) youth with DSM-IV primary diagnoses of separation anxiety, social phobia, and/or generalized anxiety disorder. Phase II involves a 6-month treatment maintenance period for Phase I responders. All subjects regardless of response status will be evaluated at all scheduled assessment points. In addition to comprehensive parent, child, clinician, and teacher reports, the primary outcome variables will be assessed by blind independent evaluators. Manualized intervention and assessment protocols plus state-of-the-art quality assurance and adverse event monitoring procedures insure uniform cross-site administration of the study protocol.

[unreadable] DESCRIPTION (provided by applicant): Anxiety disorders are common and, if untreated, influence children's lives. In randomized clinical trials (RCT), research has shown that cognitive behavioral therapy (CBT) benefits anxiety-disordered youth. We are currently comparing individual CBT, family CBT, and an education/support/attention condition. Though there has been an increase in outcome research, there has been very little study of the treatment process. With audio and video taped sessions from 154 cases that have received individual CBT in previous RCTs and 50 cases from the current trial, we will examine the relations between process variables and treatment outcome within CBT. The process variables are (1) therapeutic alliance, (2) child involvement and (3) therapist flexibility with the manual-based treatment. These three variables will be measured from sessions 1-4 (earlier process) and sessions 5-8 (later process) for the entire data set. In addition, the three process variables will be measured from sessions 9-16 for the 50 cases in the current RCT. Raters will rate the entire sessions a third at a time from a total of 1600 sessions of individual CBT using the Child Psychotherapy Process Scale, Child Involvement rating scales and the Modified Protocol Adherence Checklist. It is hypothesized that a strong therapeutic alliance and high levels of child involvement will predict positive treatment outcome. The identification of mediating influences (e.g., later involvement, therapist flexibility) will further enable the outcome researcher and the practicing clinician to develop a better understanding of the causal mechanisms between therapy and the accrual of beneficial outcomes. To evaluate potential process variables that contribute to patient attrition, we will compare the early process variables for children completing treatment and those who discontinue. It is hypothesized that non-completers will have the experienced lower levels of alliance, flexibility, and involvement.

DESCRIPTION (provided by applicant): This competing continuation of the six site Child/Adolescent Anxiety Multimodal Treatment Study (CAMS), which is currently in year 3 of the 4 year award, is being submitted in response to PA-01-123 inviting collaborative research on Clinical Studies of Mental Disorders. Anxiety disorders are among the most common conditions affecting youth with point prevalence of 12-20%. The three most common childhood onset anxiety disorders, separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SP), routinely co-occur and cause clinically significant impairment in academic, social, and family functioning. Left untreated, they foretell persistent anxiety, major depression and substance abuse into adulthood. Hence, effective treatments for childhood-onset anxiety disorders promise to alleviate and perhaps to prevent morbidity and even mortality. In randomized controlled trials, members of our group have shown that cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitors (SSRIs) are effective for anxiety disorders in youth. To date there are no controlled trails comparing CBT and an SSRI, alone and in combination, to a suitable control condition in the same patient population. CAMS is a two phase, masked, randomized controlled trial for youth ages 7-17 years with SAD, SP and GAD. Phase I is a 12-week, acute efficacy study; subjects are randomized (2:2:2:1) to CBT, sertraline, their combination or pill placebo. Phase II involves a 6-month maintenance phase for Phase I responders. We employ manualized intervention and assessment protocols, including the assessment of adverse events, and state-of-the-art quality assurance procedures that insure uniform cross-site administration of the study protocol. All subjects are evaluated at all assessment points for both beneficial and adverse outcomes. Assessments include parent, child and clinician ratings; to preserve study blindness, the primary outcomes are assessed by blind independent evaluators. The proposed competing continuation, which builds on demonstrated feasibility in sample recruitment and retention, will extend CAMS for 24 months and expand the CAMS sample from 318 to 478 subjects to increase power (1) to precisely estimate effect size differences on the primary dependent measures and (2) to promote the identification of subgroup differences (moderator analyses) and mechanisms of treatment response (mediator analyses).

DESCRIPTION (provided by applicant): The goal of this R34 is to develop a brief version of CBT (BCBT) for anxiety disorders in 7- 13 year old youth and to evaluate the feasibility of enrolling, retaining, and treating the youth with BCBT. Having an anxiety disorder in youth is associated with a higher likelihood of mental health problems in adulthood and treating youth with anxiety disorders may reduce the likelihood of subsequent problems. Currently, both cost and time are potential barriers to implementation and dissemination of treatment for anxiety disorders in youth (Egger &Burns, 2004). Treatment efficiency and accessibility may be improved with the availability of a brief form of CBT. The present project includes two phases. Phase I involves the design, development, and refining of BCBT intervention materials for anxious youth, including a therapist treatment manual and a child treatment workbook. The intervention strategies and treatment components to be included in BCBT will be chosen based on available research and expert reviews. Specifically, the 16-week CBT program will be shortened to an 8-week program by including those treatment components having received the strongest research support and the strongest endorsement from expert reviewers. In Phase I, the expert reviews will be iterative: reviewing initial materials and the revised materials. The goal is a research-guided determination of the features to be included in BCBT. The BCBT program will be evaluated during Phase II using a sample of 20 youth with a primary anxiety diagnosis of Separation Anxiety Disorder, Generalized Anxiety Disorder, or Social Phobia. We will examine BCBT for anxious youth by assessing rates of recruitment and retention of participants, as well as therapist adherence, acceptance, and deviation from the BCBT protocol. Pre- and post-treatment evaluations, as well as two- and four-month follow-up evaluations, will be conducted by independent evaluators using multiple methods of assessment. Analyses will be conducted to estimate the degree of change and variability of response to BCBT on primary outcome measures (e.g., diagnoses derived from structured diagnostic interview data, Clinician Severity Ratings). Expert evaluations in Phase II will include reviewing randomly selected treatment cases in their entirety (i.e. all sessions). Public Health Relevance Statement: Anxiety in youth is among the most prevalent forms of psychopathology in childhood (Costello, Mustillo, Erkanli, Keeler, &Angold, 2003);yet, currently fewer than half of children with anxiety disorders are receiving care (Chavira, Stein, Bailey, &Stein, 2004). The creation of a brief CBT program for anxious youth could potentially make dissemination more feasible by reducing treatment costs as well as increasing the number of clients for whom a trained therapist could provide services.

DESCRIPTION (provided by applicant): Anxiety disorders are the most common psychiatric illnesses in youth with prevalence rates averaging 5-20%. These disorders are associated with significant short- and long-term impairment in academic, familial, social, and psychological functioning. Although medication and cognitive-behavioral therapy (CBT) have been found to be effective in the short term, questions remain regarding the durability of treatment effects and the relative impact of intervention on long-term functioning. This competing continuation application (in response to PAR- 09-153) will continue the successful multi-site collaboration of the Child/Adolescent Anxiety Multi-modal Study (CAMS) group to conduct a 5-year follow-up of the sample of youth with anxiety disorders that participated in the CAMS trial. The six sites are: New York State Psychiatric Institute; Duke University Medical Center; Johns Hopkins University; Temple University; University of California at Los Angeles; and Western Psychiatric Institute and Clinic. The central questions of the proposed study, entitled the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), are to examine the long-term psychiatric, physical, and functional outcomes of youth with anxiety disorders who were randomized to one of four treatment conditions (i.e., CBT, sertraline [SRT], pill placebo, or combined CBT + SRT). CAMS succeeded in randomizing 488 children/adolescents. The CAMELS is critical in light of the need for additional information about the effects of successful treatment on the course of anxiety symptoms and their sequelae and the NIMH priority to understand the developmental trajectories of mental illness (US DHHS, 2008). CAMELS will enroll the largest sample of carefully characterized youth with anxiety disorders and will inform the field about: 1) the preventive effects of successful treatment (psychosocial; medication) on the development of later psychopathology, 2) treatment durability, 3) potential long-term adverse effects (e.g., from chronic use of medication), and 4) predictors of relapse or long-term maintenance. Findings will also be used to refine current treatments, shedding light on how existing interventions may need to be augmented or personalized to target specific distal psychopathology and/or functional outcomes for specific children.

DESCRIPTION (provided by applicant): An important movement supported by the American Psychological Association (APA) and the American Academy of Child and Adolescent Psychiatry (AACAP) is the provision of evidence-based practice (EBP) to youth with mental health needs. However, research suggests that youth do not receive EBP in the community. The school setting may be a preferred service provision setting in which to transport EBP given that youth spend the majority of their time at school and qualified individuals (e.g., school counselors, school psychologists) are available to provide services. The proposed study is a [three-phase] five-year project examining the transportation, implementation, and sustainability of a computer-assisted cognitive-behavioral treatment (CACBT) for youth anxiety. CACBT is a computer-assisted version of cognitive-behavioral treatment for child anxiety, an EBP. The study uses a cohort-sequential design and follows [20] separate schools for three years each within a five-year period, with a total of [80 therapist] participants. Each school will provide at least four individuals (e.g., counselors, social workers, school psychologists, and teachers) who can implement the intervention. [Phase I involves one semester of data collection to determine the prevalence of anxiety disorders in 1st to 4th grade children and document the schools'usual approach for addressing anxiety disorders in children (Treatment-As-Usual: TAU). Phase II involves one semester of training school personnel in the implementation of CACBT. Any child in 1st to 4th grade with distressing anxiety, as assessed by teacher-report via the Behavioral Assessment System for Children, Second Edition, Teacher Rating Scale (BASC-2 TRS), will be invited to participate. Phase III involves two years of data collection to (a) examine the sustainability of the program (i.e., the school's continued use of CACBT and the BASC-2 TRS) and (b) evaluate organizational social context variables as predictors of sustainability of CACBT and the BASC-2 TRS. The outcome of the project will be measured in terms of school personnel's increased use of CACBT and increased identification of youth with distressing anxiety via the BASC-2 TRS. Systems variables (e.g., culture, organizational climate) will be assessed as predictors of sustainability. Exploratory variables (e.g., therapist training, knowledge, adherence, skill) that may differentially affect the transportation of EBP to school settings will also be examined.] The results of the proposed study will inform the field regarding the dissemination, implementation, and sustainability of EBP in the school setting. PUBLIC HEALTH RELEVANCE: The proposed project will improve public health by increasing access to an empirically-supported treatment (cognitive-behavioral therapy for child anxiety). By disseminating this treatment into schools we will not only expand the number of youth who are served by this treatment but also train new personnel to administer it.

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) are common neurodevelopmental syndromes affecting 1% of U.S. children. Comorbid anxiety disorders affect 40 to 50% of children with ASD, causing substantial distress and impairment over and above that caused by ASD alone. High anxiety is associated with increased severity of ASD symptoms and social maladjustment in affected youth. Further, parents of children with ASD consider anxiety- related problems to be among the top two challenges facing their children. [Although standard practice cognitive-behavioral therapy (CBT) has been established as an efficacious and safe treatment for anxiety disorders among typically developing youth, its utility in comorbid cases with ASD remains unknown. To date, no studies have experimentally compared standard practice CBT to a cognitive-behavioral intervention that has been personalized for children with a comorbid presentation of anxiety and ASD.] This gap in the literature is of particular concern because there are no empirically-supported treatment options for youth with ASD and comorbid anxiety, and existing pharmacological interventions may have some disadvantages (e.g., limited efficacy in this population, side effects, and potential for drug x drug interactions). [Accordingly, we are proposing a randomized controlled trial to be conducted at three treatment sites to evaluate the efficacy of personalized CBT for anxiety in ASD (Behavioral Intervention for Anxiety in Children with Autism: BIACA) relative to standard practice CBT for anxiety (Coping Cat program). Over the last five years, the proposed BIACA intervention has been adapted and tailored to the characteristics and needs of high-functioning children with ASD; the Coping Cat program reflects the community standard that has been empirically supported in multiple NIH-funded trials.] In response to the NIH Roadmap Initiative, BIACA employs a modular treatment approach, allowing the intervention to be personalized to each youngster's unique needs. [Thus, the proposed research will: (1) examine the efficacy of BIACA relative to Coping Cat, which represents standard practice treatment, (2) evaluate the maintenance of treatment gains, (3) examine the impact of personalized intervention on functional outcomes such as social responsiveness, loneliness, and friendship quality, (4) test autism severity as a moderator of treatment outcome, and (5) explore other moderators and mediators of treatment outcome.] A total of 180 youth (ages 8-13 years) with ASD and co-occurring anxiety will be randomly assigned to one of the two treatment conditions. The three recruitment sites for this study are UCLA, the University of South Florida (USF), and Temple University. USF will provide data management services. Considering the rising number of children diagnosed with ASD together with the frequency and severity of comorbid anxiety, the proposed work is tailored to the unique needs of youth with ASD and will provide a timely contribution to public health efforts.