An Open Trial of Cognitive-Behavioral Therapy for Anxiety Disorders in Adolescents With Autism Spectrum Disorders

Abstract

The frequent co-occurrence of anxiety disorders and autism spectrum disorders (ASD) in youth has spurred study of intervention practices for this population. As anxiety disorders in the absence of ASD are effectively treated using cognitive-behavioral therapy (CBT) protocols, an initial step in evaluating treatments for comorbid youth has necessarily centered on adaptation of CBT. One primary limitation of this research, to date, is that interventions for adolescents with anxiety disorders and ASD have not been systematically tested. In this study, 20 adolescents (90% male) with ASD and a comorbid anxiety disorder, between ages 11 and 14 years (M = 12.2 years, SD = 1.11 years), participated in an open trial of modified CBT targeting anxiety with ASD. Findings demonstrated significant reductions in anxiety severity, as assessed by clinician and parent ratings, from baseline to post-treatment. In addition, reductions in parent-rated externalizing symptoms were observed. Gains were maintained at a 1-month follow-up.

Keywords

autism spectrum disorders anxiety comorbid conditions evidence-based practices

Autism is a neurobiological disorder characterized by deficits in social communication and language, as well as restricted and repetitive behaviors or interests (American Psychiatric Association [APA], 2000). In the United States, prevalence rates of autism spectrum disorders (ASD) are currently estimated at 1 in 50 children and adolescents (Center for Disease Control, 2012). These prevalence rates emphasize the need for not only a better understanding of ASD etiology but also effective psychosocial interventions. This may be particularly true for adolescents with ASD, given that prior research has largely focused upon the functioning and treatment of younger children (Schall & McDonough, 2010). Indeed, adolescents with ASD may face unique stressors compared with younger children with ASD, including poor self-care skills, increased social and vocational responsibilities, a lack of regularly paying jobs, and dependence on family for support, all of which may influence a maladaptive trajectory (Howlin, Goode, Hutton, & Rutter, 2004; Howlin, Mawhood, & Rutter, 2000). Therefore, interventions that are tailored to address the specific deficits and stressors encountered by adolescents with ASD are needed.

Among adolescents without ASD, anxiety disorders increase in frequency throughout this developmental period (Essau, Conradt, & Petermann, 2002), with many such disorders having their peak time of onset in adolescence. When considering youth with ASD, comorbid psychiatric disorders are considered the rule rather than the exception (de Bruin, Ferdinand, Meester, de Nijs, & Verheij, 2007; Leyfer et al., 2006; Meyer, Mundy, Van Hecke, & Durocher, 2006), resulting in complex and often severe clinical presentations (de Bruin et al., 2007; Klin, Paulis, Schultz, & Volkmar, 2005; Muris, Steerneman, Merckelbach, Holdrinet, & Meesters, 1998).

Anxiety disorders are particularly comorbid among ASD youth. For instance, anxiety is estimated to affect between 30% and 80% of children with ASD (e.g., de Bruin et al., 2007). Among the specific anxiety disorders, generalized anxiety disorder (GAD; estimated to affect at least 35% of those with ASD), separation anxiety disorder (SAD; 38%), obsessive-compulsive disorder (OCD; 37%), and social phobia (SP; 30%) are particularly prominent in this population (de Bruin et al., 2007; Green, Gilchrist, Burton, & Cox, 2000; Klin et al., 2005; Leyfer et al., 2006; Muris et al., 1998). An additional testament to the high comorbidity of anxiety and ASD is the observation that anxiety has been cited as the second most concerning problem reported by parents of youth with ASD (Mills & Wing, 2005).

A comorbid diagnosis of anxiety has been associated with significant functional impairment and heightened maladaptive symptomatology in children and adolescents with ASD (Attwood, 2003a; Klin et al., 2005; Sofronoff & Attwood, 2003; Volkmar & Klin, 2000). In two Research Units on Pediatric Psychopharmacology (RUPP) Autism Network medication trials, pretreatment evaluations of participants with ASD showed that higher parent-rated anxiety was associated with greater impairments in social responsiveness (RUPP Autism Network, 2002, 2005). Similarly, Bellini (2004) found that youth with ASD and higher levels of anxiety demonstrated more severe social skills deficits. Furthermore, several large studies of ASD youth have found positive associations between anxiety and severity of ASD symptomatology, such as repetitive behaviors (e.g., Sukhodolsky et al., 2008), sensory symptoms (Ben-Sasson et al., 2008), and total ASD symptoms. These associations were significant even when controlling for cognitive impairments, social maladjustment, and speech difficulties (Kelly, Garnett, & Attwood, 2008). In addition to ASD-specific impairments, the presence of anxiety disorders is also associated with worse school attendance, lower family cohesion, and poorer academic performance (e.g., Kearney, 2007; Langley, Bergman, McCracken, & Piacentini, 2004). Thus, there is strong evidence that severe anxiety is associated with additional impairments for youth with ASD, indicating a need for effective interventions targeting this common comorbidity.

Cognitive-behavioral therapy (CBT) is an efficacious psychosocial treatment for anxiety and other related emotional disorders (i.e., major depressive disorder) among typically developing youth (David-Ferdon & Kaslow, 2008; Silverman, Pina, & Viswesvaran, 2008). For children and adolescents with anxiety disorders, CBT demonstrates effect sizes comparable with those of selective serotonin reuptake inhibitor (SSRI) medication and even greater effect sizes in combination with such medications (Walkup et al., 2008). In addition, CBT has demonstrated impressive results in the treatment of child and adolescent OCD (Franklin et al., 2011; Pediatric OCD Treatment Study [POTS] Team, 2004; Storch et al., 2007), depression (March et al., 2004, 2007), and disruptive behavior disorders (e.g., Eyberg, Nelson, & Boggs, 2008). Despite these encouraging results, clinical trials that have established the efficacy of CBT in varied psychiatric conditions have routinely excluded youth with ASD. Therefore, it remains unclear whether the powerful treatment effects associated with CBT in other domains of youth psychopathology can be attained in the treatment of young adolescents with ASD.

However, youth with ASD may present unique challenges that limit the effectiveness of standard CBT. For instance, poor social skills, poor self-care and organizational skills, and restricted interests and stereotypies may interfere with successfully completing typical CBT assignments, such as going on sleepovers or play dates (e.g., Klin et al., 2007). Therefore, such deficits should be addressed before applying more standard CBT skills. Modifications to CBT interventions with ASD youth have included increased parental involvement, incorporation of social skills training, increasing independence in self-care skills, inclusion of circumscribed interests as incentives, and generalization of skills to the school environment.

Prior work has suggested that such modified CBT protocols are indeed effective in reducing anxiety symptoms in children with ASD (Chalfant, Rapee, & Carroll, 2007; Reaven, Blakeley-Smith, Culhane-Shelburne, & Hepburn, 2012; Sofronoff, Attwood, & Hinton, 2005; Storch et al., 2013; Sung et al., 2011; Wood, Drahota, Sze, Har, et al., 2009). For instance, Reaven et al. (2012) compared a modified group CBT intervention with treatment-as-usual (TAU) among 50 children ages 7- to 14 years old with an ASD. Children in the treatment group showed greater reductions in clinician severity ratings of their principal anxiety disorder diagnosis, and were more likely to be free of anxiety disorder diagnoses at post-intervention, compared with children in the TAU condition. Similarly, Wood, Drahota, Sze, Har, et al. (2009) compared a modified, modular CBT intervention with a 3-month waitlist among 40 children ages 7- to 11 years old with an ASD. The CBT intervention outperformed the waitlist control on measures of clinician-rated diagnostic severity and parent reports of the child’s anxiety, but not child self-report of anxiety.

While these trials are indeed promising, few of them have included older children and adolescents as a primary sample. Therefore, the effects of modified CBT for anxiety disorders among early adolescents with ASD remain largely unknown. As noted earlier, adolescents with ASD may face unique challenges compared with younger children, including increased social and vocational responsibilities (Howlin et al., 2004), which may certainly be impaired by the combination of ASD and anxiety symptoms if left untreated.

The goal of the present study was to evaluate the appropriateness and preliminary effects of a CBT package originally developed for younger children with adolescents and families in the context of an open trial. The Behavioral Interventions for Anxiety in Children with Autism manual (BIACA) was evaluated in a prior randomized controlled trial (RCT) for younger children with autism and an anxiety disorder (e.g., Wood, Drahota, Sze, Har, et al., 2009). The goals of this treatment are to reduce or eliminate anxiety symptoms while circumventing or managing autism-specific symptoms (e.g., poor social and self-help skills) that could contribute to anxiety severity. One aim of the present open trial investigation was to determine whether BIACA, in its original form, would be feasible and evidence preliminary efficacy with younger adolescents. Therefore, only minor, language-based modifications were made to the BIACA protocol to be developmentally appropriate for anxious adolescents who have autism at this stage of evaluation. We hypothesized that the effects of this treatment modality would be similar to those in the Wood, Drahota, Sze, Har, et al. (2009) trial and that additional effects in other areas of psychopathology and impairment beyond anxiety would be evidenced, including effects on non-targeted symptom areas (e.g., externalizing symptoms).

Method

Participants

Twenty adolescents (18 males [90% of sample]), between the ages of 11 and 14 years (M = 12.2 years, SD = 1.11 years), and their parents were recruited through two research sites: 9 at the University of California—Los Angeles (UCLA) Center for Autism Research and Treatment (all males) and 11 at the University of Southern Florida (USF) Rothman Center for Neuropsychiatry (9 males, 2 females). Youth were identified as 80% White, non-Hispanic, 15% Hispanic/Latino, and 5% Asian American. Diagnostically, all youth met criteria for a principal anxiety disorder (see Table 1) with a clinical severity level above 3 (M = 5.40, SD = 0.88) as determined by the Anxiety Disorders Interview Schedule for the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; APA, 1994), Child Version, Child- and Parent-Report Forms (ADIS-IV-C/P; Silverman & Albano, 1996). Table 1 provides additional descriptive information by treatment site.

Table 1.

Descriptive Information.

	USF (n = 9)	UCLA (n = 11)
Gender	9 males, 0 females	9 males, 2 females
Age	M = 12.11, SD = 1.17	M = 12.27, SD = 1.10
Ethnicity
Caucasian	7 (77.8%)	9 (81.8%)
Latin/Hispanic American	1 (11.1%)	1 (18.2)
Asian American	1 (11.1%)
Autism spectrum diagnosis
Autism	4 (44.4%)	9 (81.8%)
Asperger’s syndrome	2 (22.2%)	—
Pervasive developmental disorder–NOS	3 (33.3%)	2 (18.2%)
Principle diagnosis
Social phobia	4 (44.4%)	7 (63.6%)
Obsessive-compulsive disorder	1 (11.1%)	2 (18.2%)
Separation anxiety disorder	2 (22.2%)	1 (9.1%)
Generalized anxiety disorder	2 (22.2%)	—
Oppositional-defiant disorder	—	1 (9.1%)
Youth with multiple diagnoses^a	9 (100%)	11 (100%)
Social phobia	7 (77.8%)	4 (36.4%)
Obsessive-compulsive disorder	2 (22.2%)	6 (54.5%)
Separation anxiety disorder	2 (22.2%)	4 (36.4%)
Generalized anxiety disorder	5 (55.6%)	10 (90.9%)
Oppositional-defiant disorder	2 (22.2%)	1 (9.1%)
Specific phobia	1 (11.1%)	5 (45.5%)
Major depressive disorder	1 (11.1%)	1 (9.1%)

Note. USF = University of Southern Florida; UCLA = University of California–Los Angeles; NOS = not otherwise specified.

Percentages do not sum to 100% because youth may have had more than one diagnosis.

In addition, subjects met criteria for autism, Asperger’s syndrome, or other pervasive developmental disability diagnosis, as confirmed through a diagnostic algorithm composed of the Autism Diagnostic Observation Schedule (ADOS; Lord, Rutter, DiLavore, & Risi, 1999) and the Autism Diagnosis Interview–Revised (ADI-R; Lord, Rutter, & Le Couteur, 1994). If youth received this diagnosis using the ADOS less than 6 months prior to treatment beginning, then the ADOS was not repeated. Additional inclusion criteria included being between 11 and 14 years of age and having a Full Scale IQ score of 85 or above on the Wechsler Intelligence Test for Children, 4th Edition (WISC-IV; Wechsler, 2003). Participants were excluded if (a) they were concurrently receiving psychosocial treatment including psychotherapy, social skills training with homework, or behavioral interventions (such interventions could be discontinued prior to participation); (b) they initiated an antidepressant within 12 weeks prior to treatment or an antipsychotic 6 weeks within prior to treatment (or change in established medication regimen within 8 weeks for an antidepressant or 4 weeks for an antipsychotic); (c) they evidenced clinically significant suicidality within the past 6 months; and (d) they met DSM-IV diagnostic criteria for bipolar, schizophrenia, schizoaffective disorders, or substance abuse (6 months before treatment). At the time of study enrollment, nine subjects (45%) were receiving psychotropic medication, and seven of these participants were currently receiving two or more medications. Among those receiving medication, seven participants (35%) were prescribed SSRI antidepressant medication, five subjects (25%) were receiving medication for attention-deficit/hyperactivity disorder (ADHD) symptoms (e.g., Vyvance, Strattera), two subjects (10%) were prescribed an atypical antipsychotic, one subject (5%) was prescribed a tricyclic antidepressant, and one subject (5%) was receiving anxiolytic medication.

Procedure

Families who were interested in participating in the study contacted the trained project coordinator at the UCLA and USF sites, respectively. Those families who appeared to meet inclusion/exclusion criteria and were interested in the study were scheduled for an in-person diagnostic assessment with trained clinicians. During the initial visit, written parental and child assent were reviewed and signed. Consented youth and at least one participating parent/legal guardian were then administered a clinical interview and the ADIS-IV-C/P (described in the measures section) by a trained clinician. Participants were also administered the WISC-IV, if they did not have documentation substantiating a Full Scale IQ score from an evaluation conducted in the past 3 years, as well as the ADOS and ADI-R. This battery of assessments was given over the course of 2 days. Approximately 1 week after completing the screening assessments, consented participants completed additional study questionnaires. These assessment materials (see measures) were given at baseline, mid-treatment (after the eighth session), post-treatment (after the final session), and at 1-month follow-up. An independent evaluator conducted all evaluations.

Clinicians and therapists were faculty psychologists, post-doctoral clinical psychology fellows, or doctoral students in clinical or educational psychology that had experience with and were trained in working with youth with ASD. The clinicians received individual clinical supervision, per participant, in-between sessions by the principal investigators at UCLA and USF, respectively. Additional supervision included weekly cross-site conference calls with the principal investigators and therapists.

The integrity and caliber of treatment was assessed independently. Twenty sessions (10 sessions from each treatment site) were randomly selected for adherence rating using a treatment adherence questionnaire developed for the Wood, Drahota, Sze, Har, et al. (2009) BIACA trial. After establishing accuracy with the first author, two undergraduate coders otherwise uninvolved in the investigation rated all 20 tapes. Agreement between raters was excellent (κ = .89), suggesting a high degree of treatment adherence among therapists at both treatment sites.

Treatment Program: BIACA

The BIACA, a modification of the Building Confidence manual (Wood, McLeod, Hiruma, & Phan, 2008), was used for this investigation. As noted, linguistic modifications were made to ensure appropriateness when speaking with an adolescent versus younger age clients. However, further revisions were delayed pending outcome of this initial open trial. The BIACA protocol follows a modular approach, meaning that all patients receive the same core CBT components (e.g., psychoeducation, cognitive restructuring, in vivo exposure), but that the sequencing of sessions may vary among participants, depending upon individual client needs. Modularized approaches to CBT have demonstrated superiority and improved responsiveness to clinical heterogeneity versus standard CBT protocols (e.g., Weisz et al., 2012). Within this modular framework, the intervention consists of 16 weekly sessions lasting approximately 60 to 90 min each. Approximately 30 min of each session are spent with the adolescent, followed by 30 min with the parent. There are 14 child modules and 12 parent modules. The modules available for the BIACA protocol are presented in Table 2.

Table 2.

BIACA Child and Parent Modules.

Child module	Content
1	Introduction and Information about ASD
2	“K” and “I” steps
3	“C” step
H	Hierarchy of exposures
4	Second “K”—Keep practicing
KICK	Using the K.I.C.K. plan
IV	In vivo exposure
R	Relaxation
FRND (supplemental)	Making friends
SOC-C (supplemental)	Social coaching exposure
ERP (supplemental)	E/RP in vivo exposure
MENTOR (supplemental)	Mentor skills in vivo exposure
X (if needed)	Support/emergency session
T	Termination
Parent module	Content
1	Introduction and information about the treatment plan
IEP	Parent advocacy and IEP goals
IND	Encouraging independence
H	Hierarchy of exposures
EXP	Negotiating exposures
REW	Rewards
SOC-C (supplemental)	Social coaching
PLAY (supplemental)	Play dates/friendships
APPROP (supplemental)	Socially appropriate activities
MENTOR (supplemental)	Mentoring
X (if needed)	Support/emergency session
T	Termination

Note. K.I.C.K. = Knowing I’m Nervous, Icky Thoughts, Calm Thoughts, and Keep Practicing; ASD = autism spectrum disorders; IEP = individual education plan; E/RP = exposure with response prevention.

The selection of modules is determined by a treatment algorithm (see Sze & Wood, 2007). The algorithm specifies for all patients to learn a few basic coping strategies (e.g., relaxation, positive self-talk, self-reward), followed by primary focus on conducting graduated exposures derived from a fear hierarchy constructed in a collaborative fashion among the adolescent, parent(s), and therapist. Exposures are conducted continuously until anxiety symptoms have remitted. If the adolescent does not demonstrate clinical improvement following three consecutive exposure sessions, optional modules are allotted for motivation enhancement and building new coping skills. In addition, given the heterogeneity in social skill development among these patients, any social intervention module (i.e., making friends, social coaching, mentoring) can be conducted alongside exposure tasks. Furthermore, patients with comorbid OCD symptoms can also receive exposure with response prevention (E/RP) alongside in vivo exposures. Therefore, all patients receive standard CBT components (e.g., psychoeducation, cognitive restructuring, exposure), with optional modules for motivational enhancement, enhanced social skill development, short-term crisis management, or targeting obsessive and compulsive behaviors, if needed. Treatment is terminated once all targeted behaviors have improved or after 16 sessions.

In addition, a youth-friendly acronym, the K.I.C.K. Plan, is utilized to introduce common CBT principles for anxiety (e.g., psychoeducation, cognitive restructuring, relapse prevention) in a manner to help youth with high-functioning autism (HFA) remember a sequence of steps to cope with anxious situations. These include K nowing I’m Nervous, I cky Thoughts, C alm Thoughts, and K eep Practicing. In addition to these child-directed techniques, parent modules focus upon standard behavioral techniques, including encouraging independence, negotiating and planning for exposures, planned ignoring, reducing avoidance behaviors, and developing a reward list for completing exposures. Given the demanding nature of exposures, parents are instructed to develop a reward system with input from the adolescent (e.g., point system, earning privileges) to positively reinforce approach-oriented behaviors and maintain motivation throughout treatment.

Although BIACA utilizes standard child-directed and parent-directed CBT skills for youth anxiety, an important differentiation is the enhanced focus upon social skill development. This is accomplished through embedding social skills training (e.g., social coaching, facilitating get-togethers, working with school personnel to develop a “peer buddy” system) within in vivo social exposures. In addition, there is an included module targeting parent advocacy with regard to their child’s individual education plan (IEP) and obtaining academic accommodations.

The BIACA model emphasized key skills (e.g., how to treat a guest) for developmentally appropriate get-togethers and practiced positive and reciprocal social behavior skills that could be used in real-world settings, such as offering others the first turn. Finally, parent-training was addressed through parent-only sessions and in specific modules. An emphasis was made to encourage youth independence, increase communication skills, and create a toolbox of skills to diffuse problematic situations.

Measures

The Anxiety Disorders Interview Schedule for the DSM-IV–Child Version, Child and Parent–Report Forms (ADIS-IV-C/P)

The ADIS-IV-C/P (Silverman & Albano, 1996) is a semi-structured diagnostic interview that assesses all DSM-IV anxiety disorders in children and adolescents ages 7 to 17 years. The ADIS-IV-C/P also assesses unipolar depressive disorders (i.e., major depressive disorder [MDD], dysthymic disorder [DD]) and some externalizing disorders (e.g., ADHD, oppositional defiant disorder [ODD], conduct disorder). Interviews are conducted separately with the child/adolescent and the parent(s). Each diagnosis receives a clinical severity rating (CSR) on a 0-8 scale, with CSRs ≥ 4 indicating clinical levels of severity and impairment. In previous studies, the ADIS-IV-C/P has shown good psychometric properties, with strong inter-rater reliability (κ = .92; Lyneham, Abbott, & Rapee, 2007) and good test–retest reliabilities for various anxiety disorder diagnoses (κ = .80–.92; Silverman, Saavedra, & Pina, 2001). In addition, the ADIS-IV-C/P has been found to be sensitive to treatment effects (Kendall, Hudson, Gosch, Flannery-Schroeder, & Suveg, 2008). Among youth with ASD, the ADIS-IV-C/P has demonstrated excellent parent–clinician agreement (Storch et al., 2013) and convergent validity (Storch, Ehrenreich-May, et al., 2012).

Pediatric Anxiety Rating Scale (PARS)

The PARS (Research Units of Pediatric Psychopharmacology [RUPP] Autism Network, 2002) is a 50-item, clinician-administered checklist of anxiety symptoms in children and adolescents. Interviews with the child/adolescent and parent(s) are conducted, asking each respondent to indicate if each symptom was present or absent (yes/no) during the previous week. Following these interviews, clinicians integrate child and parent information to collectively rate endorsed symptoms on seven dimensions of overall severity, using a six-point scale (0 = none, 1–5 = minimal to extreme). These dimensions are as follows: (a) number of symptoms, (b) frequency of symptoms, (c) severity of distress associated with anxiety symptoms, (d) severity of physical symptoms, (e) avoidance, (f) interference at home, and (g) interference out-of-home. The total score is calculated by summing the scores of these dimensions. In previous medication trials, scores from number of symptoms and physical symptoms were excluded, given potential overlap with side effects from SSRIs. The inter-rater reliability and test–retest reliability for the PARS Total Score are sufficient (intraclasss correlation coefficient = .86 and .83, respectively). The internal consistency found in this sample (α = .52–.70) is similar to previous studies in youth with ASD (Storch, Wood, et al., 2012).

Clinical Global Impression–Severity (CGI-S)

The CGI-S (Guy, 1976) is a single-item, clinician-rated measure of overall diagnostic severity and ranges from 1 (no psychiatric illness) to 7 (extremely severe). The CGI-S is commonly used in clinical trials for youth internalizing disorders (e.g., Keller et al., 2000; March et al., 2004), and correlates well with self-reported anxious and depressive symptoms (Zaider, Heimberg, Fresco, Schneier, & Liebowitz, 2003).

In addition, the CGI-S has been shown to be effective in detecting treatment changes among youth (Storch et al., 2010). The CGI-S was completed by an independent evaluator who was not involved in the adolescent’s treatment.

Clinical Global Impression–Improvement (CGI-I)

The CGI-I (Guy, 1976) is a single-item, clinician-rated measure of overall diagnostic improvement and ranges from 1 (very much improved) to 7 (very much worse). Consistent with other clinical trials (e.g., Walkup et al., 2008), treatment responders were classified as those rated either a 1 (very much improved) or 2 (much improved). The CGI-I was rated at mid-treatment, post-treatment, and at 1-month follow-up by an independent evaluator.

Revised Child Anxiety and Depression Scale (RCADS)

The RCADS (Chorpita, Yim, Moffit, Umemoto, & Francis, 2000) is a 47-item, self-report measure of child/adolescent anxiety and depressive symptoms. The RCADS contains six subscales derived from DSM-IV criteria: (1) SAD, (2) social phobia, (3) GAD, (4) OCD, (5) panic disorder, and (6) MDD. The RCADS has previously demonstrated good internal consistency (average Cronbach’s α = .77; Chorpita et al., 2000), and has shown good validity in discriminating between anxiety and depression symptoms (Chorpita et al., 2000). In this sample, internal consistency was found to be excellent across all time points (α = .93-.96). Adolescents read and responded to RCADS items in a written format.

Child Behavioral Checklist (CBCL)

The CBCL (Achenbach & Rescorla, 2001) is a 113-item, parent-report measure of their child/adolescent’s broad internalizing and externalizing behaviors. Parents are instructed to select the degree to which each item describes their child/adolescent using very true or often true (2), somewhat or sometimes true (1), or not true (0). Higher scores reflect more severe emotional or behavioral problems. The CBCL consists of an Internalizing Problems Scale (composed of Withdrawn, Somatic Complaints, and Anxious/Depressed subscales), an Externalizing Problems Score (comprised of Delinquent Behavior and Aggressive Behavior subscales), and a Total Score (consisting of the Internalizing and Externalizing Problems Scale as well as the Social Problems, Attention Problems, and Thought Problems subscales). The CBCL is one of the most widely used broadband measures of child/adolescent emotional and behavioral problems (Achenbach, 1995; Achenbach, Dumenci, & Rescorla, 2003). The Internalizing and Externalizing scales of the CBCL have shown good internal consistency among clinically anxious and depressed youth (α = .82 and α = .76, respectively; Franco, Saavedra, & Silverman, 2007). In the current sample, internal consistency for the CBCL total score was found to be excellent at baseline (α = .95), post-treatment (α = .95) and good at one-month follow-up (α = .87).

Results

Preliminary Analyses

Demographic and clinical variables were systematically checked for patterns of missing data. There were no missing data at baseline; in total, three participants (two male subjects and one female subject) dropped out of the study prior to the post-treatment assessment and were lost to further follow-up (15% attrition). Missing data were imputed using multiple imputation (MI) with five iterations. MI is considered superior to other missing data procedures, including single imputation, mean substitution, or listwise deletion, due to less biased parameter estimates and avoiding reduction in statistical power (Enders, 2010). Analysis of missing data patterns revealed that data were missing at random, indicating that use of MI was appropriate. Pooled t values across iterations were calculated when analyzing significance levels.

Analyses of site differences in demographic and clinical variables were examined. Chi-square analyses revealed no differences in regard to ethnicity, gender, or principal diagnosis. However, t test analyses revealed that participants at the UCLA site (M = 5.91, SD = 0.54) had higher principal disorder CSR values than participants at the USF site (M = 4.78, SD = 0.83), t(18) = 3.67, p < .01. Given that the UCLA site appeared to be more severe at baseline, a between-subjects repeated measures ANOVA was conducted to determine if there was a site difference in the rate of change of principal CSR from pre- to post-treatment. No site difference was found, and thus, analyses were conducted for the entire sample, F(1,2) = .02, p = ns.

Primary Outcomes

PARS

Descriptive statistics for each measure at baseline, post-treatment, and at 1-month follow-up are presented in Table 3. Due to the large number of paired comparisons (n = 22), Bonferroni-adjusted alpha levels of .002 (.05/22) were used to test for statistical significance. A dependent t test was conducted to examine if PARS scores significantly changed from baseline to post-treatment. Analyses revealed that mean total scores at post-treatment (M = 10.94, SD = 3.33) were significantly lower compared with baseline (M = 16.50, SD = 3.00), t(19) = 8.39, p < .001, d = 1.76 (Cohen, 1988). There was no significant difference between post-treatment and 1-month follow-up PARS scores, indicating that treatment gains were maintained, t(19) = −1.71, p = ns.

Table 3.

Means, Standard Deviations, p Values, and Effect Sizes for Outcome Measures.

Scale	Pre-treatment	Post-treatment	p value*	Effect size	1-month follow-up	p value	Effect size
Scale	M (SD)	M (SD)	p value*	Cohen’s d	M (SD)	p value	Cohen’s d
PARS	16.50 (3.00)	10.94 (3.33)	<.001	1.76	12.36 (3.59)	ns	—
CSR	5.29 (0.92)	4.35 (1.58)	<.001	0.73	4.17 (1.12)	ns	—
CGI-S	4.29 (0.99)	3.06 (1.20)	<.001	1.12	2.64 (1.03)	ns	—
CBCL-Total	59.56 (26.72)	42.38 (22.72)	<.001	0.69	30.11 (14.90)	ns	—
CBCL-Int	20.69 (7.90)	15.94 (9.57)	<.001	0.54	9.67 (5.85)	ns	—
CBCL-Ext	10.63 (11.44)	5.69 (5.34)	Ns	—	5.56 (5.83)	ns	—
CBCL-Anx/Dep	10.13 (3.67)	7.50 (3.43)	<.001	0.74	5.56 (2.70)	ns	—
CBCL-Social	7.94 (3.40)	6.13 (4.13)	Ns	—	3.33 (3.24)	<.001	0.75
CBCL-With	6.19 (3.25)	4.63 (3.26)	Ns	—	2.11 (2.37)	ns	—
CBCL-Som	4.38 (3.91)	3.18 (4.62)	Ns	—	2.00 (2.18)	ns	—
RCADS-Tot Anx	29.29 (17.07)	22.00 (18.17)	Ns	—	18.60 (15.50)	ns	—
RCADS-Tot Anx/Dep	37.12 (21.73)	28.65 (22.44)	ns	—	25.30 (20.63)	ns	—

Note. PARS = Pediatric Anxiety Rating Scale; CSR = Clinician Severity Rating; CGI-S = Clinician Global Impression–Severity; CBCL-Total/Int/Ext/Anx-Dep/Social/With/Som = Child Behavior Checklist–Total/Internalizing/Externalizing/Anxious–Depressed Behavior/Social Problem/Withdrawn–Depressed/Somatic Complaints; RCADS-Tot Anx/Tot Anx-Dep = Revised Child Anxiety and Depression Scales–Total Anxiety/Total Anxiety and Depression score.

Significance level adjusted for multiple comparisons.

Principal diagnosis on the ADIS-IV-C/P

A dependent t test was performed to analyze the change in principal disorder CSR values from baseline to post-treatment on the ADIS-IV-C/P. Analyses revealed a significant reduction in principal CSR values from baseline (M = 5.28, SD = 0.92) to post-treatment (M = 4.35, SD = 1.58), t(19) = 3.25, p < .001, d = 0.73 (medium effect). However, among treatment completers (n = 17), only three participants (17.65%) achieved remission of their principal anxiety disorder (i.e., were assigned CSRs ≤3). There was no significant change in principal CSR scores from post-treatment to 1-month follow-up, indicating that treatment gains were maintained, t(19) = 0.33, p = ns. At 1-month follow-up, four subjects (23.53%) no longer met criteria for their principal anxiety disorder.

CGI-S and CGI-I

A dependent t test was performed to compare CGI-S values at baseline and post-treatment. Analyses demonstrated that CGI-S scores were significantly lower at post-treatment (M = 3.06, SD = 1.20), as compared with baseline (M = 4.29, SD = 0.99), t(19) = 5.48, p < .001, d = 1.12. There was no significant difference between CGI-S scores at post-treatment and 1-month follow-up, indicating that treatment gains were maintained, t(19) = 1.59, p = ns.

In addition, among treatment completers (n = 17), while only 3 participants (16.67%) had achieved responder status by mid-treatment as indicated by ratings on the CGI-I, 13 participants (76.47%) achieved responder status at post-treatment. Among those completing 1-month follow-up (n = 11), 8 participants (72.73%) were classified as treatment responders.

Secondary Outcomes

Additional dependent t tests were conducted to analyze changes in parent-reported CBCL scores and adolescent-reported RCADS scores. Analyses revealed a significant decrease in CBCL Total scores from baseline to post-treatment, t(19) = 11.72, p < .001, d = 0.69. In addition, significant decreases from baseline to post-treatment were observed in CBCL Externalizing Problem scores, t(19) = 1.48, p < .001, d = 0.55, CBCL Anxiety/Depression scores, t(19) = 4.09, p < .001, d = 0.74, and CBCL Attention Problems scores, t(19) = 3.68, p < .001, d = 0.77. Changes in all other CBCL subscale scores from baseline to post-treatment were non-significant. Treatment gains were maintained at 1-month follow-up. Notably, although there were no significant changes in CBCL Social Problems scores from baseline to post-treatment, there was a significant reduction in CBCL Social Problems scores from post-treatment to 1-month follow-up, t(19) = 2.82, p < .001, d = 0.77. In contrast to parent-rated symptomatology, there were no significant changes in adolescent-rated RCADS Total scores, or any RCADS subscale scores, from baseline to post-treatment.

Discussion

This study was an initial investigation into the effectiveness of a modified CBT protocol for anxiety disorders for adolescents with ASD. Results from this open trial demonstrated significant reductions in principal anxiety disorder severity scores, clinician-rated overall anxiety symptoms, and clinician-rated overall clinical severity, from baseline to post-treatment, and in clinician-rated overall impairment at post-treatment. In addition to these primary outcomes, reductions in parent-rated internalizing and externalizing symptoms were observed. Treatment gains were maintained at 1-month follow-up.

Findings from this open trial offer preliminary support for utilizing the BIACA protocol in treating anxiety disorders among adolescents with ASD. Results were consistent with findings from other RCTs, demonstrating significant reductions in anxiety severity among younger children with ASD (e.g., Wood, Drahota, Sze, Van Dyke, et al., 2009). However, this was the first known trial to directly assess the effectiveness of modified CBT for anxiety exclusively among an older ASD population. Given the unique stressors and treatment needs for individuals with ASD during this developmental period, particularly those with diagnostic comorbidity, findings from this open trial offer promise for adolescents with ASD and comorbid anxiety disorders.

Although most hypotheses were supported, three somewhat unexpected findings emerged. First, a discrepancy was noted between those that achieved remission of their anxiety disorder diagnosis at post-treatment and follow-up evaluations and the much higher percentage that were considered treatment responders on the CGI at both these assessment points. Discrepancies between the numbers of treatment responders and those that completely remit from an anxiety disorder are also common in the literature on cognitive-behavioral interventions for typically developing youth (e.g., Ginsburg et al., 2011). As well, other trials of anxiety-focused interventions for youth with ASD have also demonstrated some retention of clinical anxiety severity following treatment (Wood, Drahota, Sze, Har, et al., 2009). These findings might also be attributable to the foci of measurement between the CSR from the ADIS-IV-C/P, which very specifically addresses the degree of anxiety-related severity and distress currently endorsed by adolescents and their parents, and the degree to which the same informants and independent evaluators perceived their relative improvement overall from baseline on the CGI-I. However, one may also conclude that anxiety-related distress may be less likely to completely remit following CBT among early adolescents, although significant improvements in their functioning overall are likely to occur. Further study using a RCT design will likely help clarify the latter possibility. In addition, future research should examine the feasibility of implementing a modified CBT intervention for youth with HFA in settings that may be more accessible or cost-effective, such as training counselors to deliver the intervention in schools.

Second, there were no significant changes in adolescent-rated anxiety and depression symptoms. However, analysis of descriptive statistics revealed a downward trend in reported anxiety and depression, but which failed to reach statistical significance. This may be the result of lowered statistical power, given the small sample size, as well as the use of a conservative alpha level (.002) due to controlling for multiple comparisons. Thus, it is possible these symptom changes would have reached statistical significance in a larger sample. Alternatively, it may be that early adolescents with ASD struggle to report on internalizing symptoms due to a variety of reasons (e.g., cognitive features secondary to ASD, reduced insight; Storch et al., in press) resulting in less precise estimates of symptom severity. Third, there were no significant changes in parent-rated social problems from baseline to post-treatment, but there was a significant reduction at 1-month follow-up. It is possible that improvements in social functioning may not be evident at the end of treatment, but rather require a longer period of practice of treatment skills in order for others to observe significant changes.

While promising, findings should be considered in light of study limitations. First, this was an open trial, and thus treatment comparisons with a control condition are not possible. As such, it is possible that findings could be explained by regression to the mean or expectancy biases. Future studies utilizing a randomized controlled design, such as comparing the BIACA protocol with a waitlist control group, are certainly warranted to strengthen confidence in findings from this open trial. Second, the sample size was modest (N = 20). Future studies with larger sample sizes are needed, particularly for addressing questions regarding mediators and moderators of treatment outcomes. Third, our follow-up period of 1 month was relatively short. Thus, longer follow-up time points are recommended for future studies, to better assess long-term maintenance of treatment gains.

Despite these limitations, this open trial offers preliminary support for modified CBT for anxiety among adolescents with ASD. Such findings are notable as there are no empirically supported psychosocial or pharmacological intervention options for this subgroup available (Autism Speaks, 2009; Henry et al., 2006), despite the frequent use of pharmacological agents (Oswald & Sonenklar, 2007) that have unclear efficacy and may be accompanied by adverse effects. Future RCTs with larger samples and longer follow-up intervals are needed to garner greater empirical support for these interventions, with the ultimate goal of identifying evidence-based treatment approaches for adolescents with anxiety and ASD and their families.

Footnotes

Acknowledgements

We would like to thank Gregory Simpson, Amelia Rowley, Amy Beaumont, Josh Nadeau, Lindsay Brauer, Amy Parks, and P. Jane Mutch for their assistance, as well as the children and families who participated in this trial.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Ehrenreich-May has receievd funding from the National Institutes of Health and the Dan Marino Foundation. She receives book and product honorarium from Guilford Press, Oxford University Press and Behavioral Tech Research, LLC. Dr. Storch has received research funding in the last 2 years from the National Institutes of Health, Agency for Healthcare Research and Quality, All Children’s Hospital Guild Endowed Chair, and Janssen Scientific Affairs. He receives textbook honorarium from Springer publishers, American Psychological Association, Wiley, and Lawrence Erlbaum. He is a consultant for Prophase, Inc. and CroNos, Inc., and is on the Speaker’s Bureau for the International OCD Foundation. Dr. Lewin receives research support from the International OCD Foundation; has received travel support from The National Institute of Mental Health (NIMH) and Rogers Memorial Hospital; has received speaker’s honorarium from the Tourette Syndrome Association; has received honorarium from Springer Publishers; and is a consultant for Prophase, LLC. Dr. Piacentini has received research support from Pfizer Pharmaceuticals through the Duke University CAPTN Network. Dr. Murphy has received research support from the following: The National Institute of Mental Health (NIMH), CDC, IOCDF, Otsuka Pharmaceuticals, AstraZeneca Pharmaceuticals, Sunovion Pharmaceuticals, F. Hoffmann-LaRoche Ltd., Shire Pharmaceuticals through Yale University, Pfizer Pharmaceuticals through Duke University. She has received travel support and honorarium from the Tourette Syndrome Association. She also receives book royalties from Lawrence Erlbaum, Inc. Dr. Laugeson receives royalties for book sales from Routledge and Jossey-Bass.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research described in the manuscript was funded by a grant from the National Institute of Child Health and Human Development (R34 HD65284) to the first author, second author, and last author (principal investigators).

References

Achenbach

T. M.

(1995). Empirically based assessment and taxonomy: Applications to clinical research. Psychological Assessment, 7(3), 261.

Achenbach

T. M.

Dumenci

Rescorla

L. A.

(2003). DSM-oriented and empirically based approaches to constructing scales from the same item pools. Journal of Clinical Child and Adolescent Psychology, 32(3), 328–340.

Achenbach

T. M.

Rescorla

(2001). ASEBA School-Age Forms & Profiles. Burlington: Aseba.

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev.). Washington, DC: Author.

Attwood

(2003a). Frameworks for behavioral interventions. Child and Adolescent Psychiatric Clinics of North America, 12, 65–86.

Autism Speaks. (2009). Autism speaks announces results reported for the study of floxetine in autism (SOFIA), first industry-sponsored trial for the autism clinical trials network (ACTN). Retrieved from http://www.autismspeaks.org/about-us/press-releases/autism-speaks-announces-resultsreported-study-fluoxetine-autism-sofia

Bellini

(2004). Social skills deficits and anxiety in high-functioning adolescents with autism spectrum disorders. Focus on Autism and Other Developmental Disabilities, 19, 78–86.

Ben-Sasson

Cermak

S. A.

Orsmond

G. I.

Tager-Flusberg

Kadlec

M. B.

Carter

A. S.

(2008). Sensor clusters of toddlers with autism spectrum disorders: Differences in affective symptoms. Journal of Child Psychology and Psychiatry, 49, 817–825.

10.

Centers for Disease Control and Prevention. (2012, March). Prevalence of autism spectrum disorders. MMWR Surveillance Summaries, 61(SS03), 1–19. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm?s_cid=ss6103a1_e

11.

Chalfant

A. M.

Rapee

Carroll

(2007). Treating anxiety disorders in children with high functioning autism spectrum disorders: A controlled trial. Journal of Autism and Developmental Disorders, 37, 1842–1857.

12.

Chorpita

B. F.

Yim

Moffitt

Umemoto

L. A.

Francis

S. E.

(2000). Assessment of symptoms of DSM-IV anxiety and depression in children: A revised child anxiety and depression scale. Behaviour Research and Therapy, 38(8), 835–855.

13.

Cohen

( 1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum.

14.

David-Ferdon

Kaslow

N. J.

(2008). Evidence-based psychosocial treatments for child and adolescent depression. Journal of Clinical Child & Adolescent Psychology, 37, 62–104.

15.

de Bruin

E. I.

Ferdinand

R. F.

Meester

de Nijs

P. F.

Verheij

(2007). High rates of psychiatric comorbidity in PDD-NOS. Journal of Autism and Developmental Disorders, 37, 877–886.

16.

Enders

C. K.

(2010). Applied missing data analysis. Guilford Press.

17.

Essau

C. A.

Conradt

Petermann

(2002). Course and outcome of anxiety disorders in adolescents. Journal of Anxiety Disorders, 16, 67–81.

18.

Eyberg

S. M.

Nelson

M. M.

Boggs

S. R.

(2008). Evidence-based psychosocial treatments for children and adolescents with disruptive behavior. Journal of Clinical Child & Adolescent Psychology, 37, 215–237.

19.

Franco

Saavedra

L. M.

Silverman

W. K.

(2007). External validation of comorbid patterns of anxiety disorders in children and adolescents. Journal of Anxiety Disorders, 21, 717–729.

20.

Franklin

M. E.

Sapyta

Freeman

J. B.

Khanna

Compton

Almirall

March

J. S.

(2011). Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: The Pediatric OCD Treatment Study II randomized controlled trial. Journal of the American Medical Association, 306, 1224–1232.

21.

Ginsburg

G. S.

Kendall

P. C.

Sakolsky

Compton

S. N.

Piacentini

Albano

A. M.

. . . March

. (2011). Remission after acute treatment in children and adolescents with anxiety disorders: Findings from the CAMS. Journal of Consulting and Clinical Psychology, 79(6), 806.

22.

Green

Gilchrist

Burton

Cox

(2000). Social and psychiatric functioning in adolescents with Asperger syndrome compared with Conduct disorder. Journal of Autism and Developmental Disabilities, 30, 279–293.

23.

Guy

(1976). Clinical global impression scale. The ECDEU Assessment Manual for Psychopharmacology—Revised. Volume DHEW Publ No ADM 76, 338, 218–222.

24.

Henry

C. A.

Steingard

Venter

Guptill

Halpern

E. F.

Bauman

(2006). Treatment outcome and outcome associations in children with pervasive developmental disorders treated with selective serotonin reuptake inhibitors: A chart review. Journal of Child and Adolescent Psychopharmacology, 16, 187–195.

25.

Howlin

Goode

Hutton

Rutter

(2004). Adult outcome for children with autism. Journal of Child Psychology and Psychiatry, 45, 212–229.

26.

Howlin

Mawhood

Rutter

(2000). Autism and developmental receptive language disorder—A follow-up comparison in early adult life. II: Social, behavioural, and psychiatric outcomes. Journal of Child Psychology and Psychiatry, 41, 561–578.

27.

Kearney

C. A.

(2007). Forms and functions of school refusal behavior in youth: An empirical analysis of absenteeism severity. Journal of Child Psychology and Psychiatry, 48, 53–61.

28.

Keller

M. B.

McCullough

J. P.

Klein

D. N.

Arnow

Dunner

D. L.

Gelenberg

A. J.

Zajecka

(2000). A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. New England Journal of Medicine, 342, 1462–1470.

29.

Kelly

A. B.

Garnett

M. S.

Attwood

(2008). Autism spectrum symptomatology in children: The impact of family and peer relationships. Journal of Abnormal Child Psychology, 36, 1069–1081.

30.

Kendall

P. C.

Hudson

J. L.

Gosch

Flannery-Schroeder

Suveg

(2008). Cognitive-behavioral therapy for anxiety disordered youth: A randomized clinical trial evaluating child and family modalities. Journal of Consulting and Clinical Psychology, 76, 282–297.

31.

Klin

Paulis

Schultz

Volkmar

(2005). Three diagnostic approaches to Asperger syndrome: Implications for research. Journal of Autism and Developmental Disorders, 35, 221–234.

32.

Klin

Saulnier

C. A.

Sparrow

S. S.

Cicchetti

D. V.

Volkmar

F. R.

Lord

(2007). Social and communication abilities and disabilities in higher functioning individuals with autism spectrum disorders: The Vineland and the ADOS. Journal of Autism and Developmental Disorders, 37(4), 748–759.

33.

Langley

A. K.

Bergman

R. L.

McCracken

Piacentini

J. C.

(2004). Impairment of childhood anxiety disorders: Preliminary examination of the Child Anxiety Impact Scale-Parent Version. Journal of Child and Adolescent Psychopharmacology, 14, 105–114.

34.

Leyfer

O. T.

Folstein

S. E.

Bacalman

Davis

N. O.

Dinh

Morgan

. . .Lainhart

J. E.

(2006). Comorbid psychiatric disorders in children with autism: Interview development and rates of disorders. Journal of Autism and Developmental Disorders, 36, 849–861.

35.

Lord

Rutter

DiLavore

Risi

(1999). Autism diagnostic observation schedule-WPS edition. Los Angeles, CA: Western Psychological Services.

36.

Lord

Rutter

Le Couteur

(1994). Autism Diagnostic Interview—Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.

37.

Lyneham

H. J.

Abbott

M. J.

Rapee

R. M.

(2007). Interrater reliability of the anxiety disorders interview schedule for DSM-IV: Child and parent version. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 731–736. doi:10.1097/chi.0b013e3180465a09

38.

March

J. S.

Silva

Petrycki

Curry

Wells

Fairbank

. . .Severe

(2004). Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for adolescents with depression study randomized control trial. Journal of the American Medical Association, 292, 807–820.

39.

March

J. S.

Silva

Petrycki

Curry

Wells

Fairbank

. . .Severe

(2007). The treatment for adolescents with depression study: Long-term effectiveness and safety outcomes. Archives of General Psychiatry, 64, 1132–1143.

40.

Meyer

J. A.

Mundy

P. C.

Van Hecke

A. V.

Durocher

J. S.

(2006). Social attribution processes and comorbid psychiatric symptoms in children with Asperger syndrome. Autism, 10, 383–402.

41.

Mills

Wing

(2005, July). Researching interventions in ASD and priorities for research: Surveying the membership of the NAS. Paper presented at the annual meeting of the National Autistic Society, London, England.

42.

Muris

Steerneman

Merckelbach

Holdrinet

Meesters

(1998). Comorbid anxiety symptoms in children with pervasive developmental disorders. Journal of Anxiety Disorders, 12, 387–393.

43.

Oswald

D. P.

Sonenklar

N. A.

(2007). Medication use among children with autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 17, 348–355.

44.

Pediatric OCD Treatment Study Team. (2004). Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: The Pediatric OCD Treatment Study randomized control trail. Journal of the American Medical Association, 292, 1969–1976.

45.

Reaven

Blakeley-Smith

Culhane-Shelburne

Hepburn

(2012). Group cognitive behavior therapy for children with high-functioning autism spectrum disorders and anxiety: A randomized trial. Journal of Child Psychology and Psychiatry, 53, 410–419.

46.

Research Units on Pediatric Psychopharmacology Autism Network. (2002). Risperidone in children with autism and serious behavioral problems. New England Journal of Medicine, 347, 314–321.

47.

Research Units on Pediatric Psychopharmacology Autism Network. (2005). Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Archives of General Psychiatry, 62, 1266–1274.

48.

Schall

C. M.

McDonough

J. T.

(2010). Autism spectrum disorders in adolescence and early adulthood: Characteristics and issues. Journal of Vocational Rehabilitation, 32, 81–88.

49.

Silverman

W. K.

Albano

A. M.

(1996). Anxiety Disorders Interview Schedule for DSM-IV: Parent interview schedule (Vol. 1). Oxford University Press.

50.

Silverman

W. K.

Pina

A. A.

Viswesvaran

(2008). Evidence-based psychosocial treatments for phobic and anxiety disorders in children and adolescents. Journal of Clinical Child & Adolescent Psychology, 37, 105–130.

51.

Silverman

W. K.

Saavedra

L. M.

Pina

A. A.

(2001). Test-retest reliability of anxiety symptoms and diagnoses with the Anxiety Disorders Interview Schedule for DSM-IV: Child and parent versions. Journal of the American Academy of Child & Adolescent Psychiatry, 40(8), 937–944.

52.

Sofronoff

Attwood

(2003). A cognitive behaviour therapy intervention for anxiety in children with Asperger syndrome. Good Autism Practice, 6, 1–8.

53.

Sofronoff

Attwood

Hinton

(2005). A randomized controlled trial of a CBT intervention for anxiety in children with Asperger syndrome. Journal of Child Psychology and Psychiatry, 46, 1152–1160.

54.

Storch

E. A.

Arnold

E. B.

Lewin

A. B.

Nadeau

J. M.

Jones

A. M.

De Nadai

A. S.

. . .Murphy

T. K.

(2013). The effect of cognitive-behavioral therapy versus treatment as usual for anxiety in children with autism spectrum disorders: A randomized, controlled trial. Journal of the American Academy of Child & Adolescent Psychiatry, 52, 132–142.

55.

Storch

E. A.

Ehrenreich-May

Wood

J. J.

Jones

A. M.

DeNadai

A. S.

Lewin

A. B.

Murphy

T. K.

(2012). Multiple informant agreement on the Anxiety Disorders Interview Schedule in youth with autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 22, 292–299.

56.

Storch

E. A.

Lack

Merlo

L. J.

Marien

W. E.

Geffken

G. R.

Grabill

. . .Goodman

W. K.

(2007). Associations between miscellaneous symptoms and symptom dimensions: An examination of pediatric obsessive-compulsive disorder. Behavior Research and Therapy, 45, 2593–2603.

57.

Storch

E. A.

Murphy

T. K.

Goodman

W. K.

Geffken

G. R.

Lewin

A. B.

Henin

. . . Geller

D. A.

(2010). A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Biological Psychiatry, 68(11), 1073–1076.

58.

Storch

E. A.

Wood

J. J.

Ehrenreich-May

Lewin

A. B.

Jones

A. M.

Park

J. M.

Murphy

T. K.

(2012). Convergent and divergent validity and reliability of the Pediatric Anxiety Rating Scale. Journal of Autism and Developmental Disorders, 42, 2374–2382.

59.

Sukhodolsky

D. G.

Scahill

Gadow

K. D.

Arnold

L. E.

Aman

M. G.

McDougle

C. J.

. . . Vitiello

(2008). Parent-related anxiety symptoms in children with pervasive developmental disorders: Frequency and association with core autism symptoms and cognitive functioning. Journal of Abnormal Child Psychology, 36, 117–128.

60.

Sung

Ooi

Goh

Pathy

Fung

D. S.

Ang

R. P.

Lam

(2011). Effects of cognitive-behavioral therapy on anxiety in children with autism spectrum disorders: A randomized controlled trial. Child Psychiatry & Human Development, 42, 634–649.

61.

Sze

K. M.

Wood

J. J.

(2007). Cognitive behavioral treatment of comorbid anxiety disorders and social difficulties in children with high-functioning autism: A case report. Journal of Contemporary Psychotherapy, 37(3), 133–143.

62.

Volkmar

F. R.

Klin

(2000). Diagnostic issues in Asperger syndrome. Asperger syndrome, 27, 25–71.

63.

Walkup

J. T.

Albano

A. M.

Piacentini

Birmaher

Compton

S. N.

Sherrill

J. T.

. . .Kendall

P. C.

(2008). Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. New England Journal of Medicine, 359(26), 2753–2766.

64.

Wechsler

(2003). Wechsler Intelligence Scale for Children-WISC-IV. Psychological Corporation.

65.

Weisz

J. R.

Chorpita

B. F.

Palinkas

L. A.

Schoenwald

S. K.

Miranda

Bearman

S. K.

, . . . Research Network on Youth Mental Health. (2012). Testing standard and modular designs for psychotherapy treating depression, anxiety, and conduct problems in youth: A randomized effectiveness trial. Archives of General Psychiatry, 69(3), 274–282.

66.

Wood

J. J.

Drahota

Sze

K. M.

Har

Chiu

Langer

(2009). Cognitive behavioral therapy for anxiety in children with autism spectrum disorders: A randomized, controlled trial. Journal of Child Psychology and Psychiatry, 50, 224–234.

67.

Wood

J. J.

Drahota

Sze

Van Dyke

Decker

Fujii

Spiker

(2009). Brief report: Effects of cognitive behavioral therapy on parent-reported autism symptoms in school-age children with high-functioning autism. Journal of Autism and Developmental Disorders, 39, 1608–1612.

68.

Wood

J. J.

McLeod

B. D.

Hiruma

L. S.

Phan

A. Q.

(2008). Child anxiety disorders: A family-based treatment manual for practitioners. WW Norton & Co.

69.

Zaider

T. I.

Heimberg

R. G.

Fresco

D. M.

Schneier

F. R.

Liebowitz

M. R.

(2003). Evaluation of the Clinical Global Impression Scale among individuals with social anxiety disorder. Psychological Medicine, 33, 611–622.