Barriers, motivators and strategies to increase participation in genetic research among Asian and Black families of autistic individuals.

Genetic research can help advance our knowledge of autism and positively impact the progress of care for individuals with autism. Asian American and Pacific Islander (AAPI) and Black participants remain significantly underrepresented in genetic research in autism in the United States, including nationwide, multisite, genetic consortiums like Simons Foundation Powering Autism Research for Knowledge (SPARK). Few studies have explored the unique motivators and barriers that influence participation in genetics research across underrepresented groups with autism and strategies to increase participation. Therefore, the aim of this study was to understand the perspectives of AAPI and Black parents of individuals with autism about participating in genetic research, specifically motivators (e.g., desire to know more about the relationship between autism and genetics) and/or barriers (e.g., mistrust of research staff) that may impact their decision to participate in genetic research. Using a mixed-methods approach, we collected surveys (n = 134) across the United States and conducted three focus groups with parents of individuals with autism (n = 16) who identified as AAPI and Black from two large metropolitan cities. No significant differences were observed in the survey data but findings from the focus groups elucidate shared motivators for participation (e.g., to help advance the autism field for future generations) and nuanced differences in barriers that influence Black and AAPI parents' decision to participate (e.g., different beliefs about the source of autism). Practical suggestions to improve outreach and study engagement in genetic research in autism were identified and discussed.

Evidence-based recruitment strategies for clinical research: Study personnel's and research participants' perceptions about successful methods of outreach for a U.S. Autism-Research Cohort.

Introduction: Under enrollment of participants in clinical research is costly and delays study completion to impact public health. Given that research personnel make decisions about which strategies to pursue and participants are the recipients of these efforts, we surveyed research staff (n = 52) and participants (n = 4,144) affiliated with SPARK (Simons Foundation Powering Autism for Knowledge) - the largest study of autism in the U.S. - to understand their perceptions of effective recruitment strategies. Methods: In Study 1, research personnel were asked to report recruitment strategies that they tried for SPARK and to indicate which ones they would and would not repeat/recommend. In Study 2, SPARK participants were asked to indicate all the ways they heard about the study prior to enrollment and which one was most influential in their decisions to enroll. Results: Staff rated speaking with a SPARK-study-team member (36.5%), speaking with a medical provider (19.2%), word of mouth (11.5%), and a live TV news story (11.5%) as the most successful strategies. Participants most often heard about SPARK via social media (47.0%), speaking with a medical provider (23.1%), and an online search (20.1%). Research personnel's and participants' views on effective recruitment strategies often differed, with the exception of speaking with a medical provider. Conclusion: Results suggest that a combination of strategies is likely to be most effective in reaching diverse audiences. Findings have implications for the selection of strategies that meet a study's specific needs, as well as recruitment-strategy "combinations" that may enhance the influence of outreach efforts.

Effectiveness of multimodal participant recruitment in SPARK, a large, online longitudinal research study of autism.

Background: SPARK launched in 2016 to build a US cohort of autistic individuals and their family members. Enrollment includes online consent to share data and optional consent to provide saliva for genomic analysis. SPARK's recruitment strategies include social media and support of a nation-wide network of clinical sites. This study evaluates SPARK's recruitment strategies to enroll a core study population. Methods: Individuals who joined between January 31, 2018, and May 29, 2019 were included in the analysis. Data include sociodemographic characteristics, clinical site referral, the website URL used to join, how the participant heard about SPARK, enrollment completion (online registration, study consents, and returning saliva sample), and completion of the baseline questionnaire. Logistic regressions were performed to evaluate the odds of core participant status (completing enrollment and baseline questionnaire) by recruitment strategy. Results: In total, 31,715 individuals joined during the study period, including 40% through a clinical site. Overall, 88% completed online registration, 46% returned saliva, and 38% were core participants. Those referred by a clinical site were almost twice as likely to be core participants. Those who directly visited the SPARK website or performed a Google search were more likely to be core participants than those who joined through social media. Discussion: Being a core participant may be associated with the "personal" connection and support provided by a clinical site and/or site staff, as well as greater motivation to seek research opportunities. Findings from this study underscore the value of adopting a multimodal recruitment approach that combines social media and a physical presence.

The Impact of Cognitive Behavioral Therapy on Sleep Problems in Autistic Children with Co-occurring Anxiety.

PURPOSE: This study seeks to examine the relationship between anxiety-symptom severity and sleep behaviors in autistic children receiving cognitive behavioral therapy (CBT). METHODS: We conducted a secondary-data analysis from a sample of 93 autistic youth, 4 to 14 years, participating in 24 weeks of CBT. Clinicians completed the Pediatric Anxiety Rating Scale (PARS) and parents completed the Children's Sleep Habits Questionnaire, Abbreviated/Short Form (CSHQ-SF) at baseline, mid-treatment, post-treatment and 3 months post-treatment. Mediation analysis evaluated the role of anxiety symptoms in mediating the effect of time in treatment on sleep. RESULTS: There was a negative association between time in treatment and scores on the CSHQ-SF (b = - 3.23, SE = 0.493, t = - 6.553, p < 0.001). Increased time in treatment was associated with decreased anxiety (b = - 4.66, SE = 0.405, t = - 11.507, p < 0.001), and anxiety symptoms decreased with CSHQ-SF scores (b = 0.322, SE = 0.112, t = 2.869, p = 0.005). The indirect effect of time in treatment on CSHQ-SF scores through PARS reduction was negative, but not statistically significant. CONCLUSION: Increased time in CBT was associated with decreased anxiety severity and improved sleep behaviors. Reductions in anxiety symptoms may mediate improvements in sleep problems, but larger sample sizes are necessary to explore this further.

Parent-Led Cognitive Behavioral Teletherapy for Anxiety in Autistic Youth: A Randomized Trial Comparing Two Levels of Therapist Support.

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders, though to date it has been minimally tested. In this study, 87 autistic youth (7 to 13 years old) with anxiety disorders and their parents were randomized to two forms of parent-led CBT in which parents led their child through a guided CBT workbook across 12 weeks: one with low therapist contact (four 30-minute telehealth calls), and one with standard therapist contact (ten 60-minute telehealth calls). Anxiety, functional impairment, and autism features significantly declined across therapy, without differences between groups. High satisfaction was reported in both groups, though significantly higher satisfaction ratings were reported in standard-contact CBT. Responder rates were 69% of completers at posttreatment (70% in standard contact, 68% in low contact) and 86% at 3-month follow-up (86% in standard contact, 87% in low contact). Low-contact CBT was estimated to incur an average cost of $755.70 per family compared with $1,978.34 in standard-contact CBT. Parent-led CBT with minimal or standard therapist contact both appear to be effective CBT delivery formats for autistic youth with anxiety disorders, with significant cost savings for low-contact CBT.

Developmental regression in children: Current and future directions.

Developmental regression describes when a child loses previously established skills, such as the ability to speak words and is most recognised in neurodevelopmental conditions including Autism; Developmental Epileptic Encephalopathies, such as Landau Kleffner syndrome, and genetic conditions such as Rett syndrome and Phelan McDermid syndrome. Although studies have reported developmental regression for over 100 years, there remain significant knowledge gaps within and between conditions that feature developmental regression. The certainty of evidence from earlier work has been limited by condition-specific studies, retrospective methodology, and inconsistency in the definitions and measures used for classification. Given prior limitations in the field, there is a paucity of knowledge about neurocognitive mechanisms, trajectories and outcomes for children with developmental regression, and their families. Here we provide a comprehensive overview, synthesise key definitions, clinical measures, and aetiological clues associated with developmental regression and discuss impacts on caregiver physical and mental health to clarify challenges and highlight future directions in the field.

Use of a Best Practice Alert (BPA) to Increase Diversity Within a US-Based Autism Research Cohort.

We evaluated the success of a best practice alert (BPA) in recruiting underrepresented families into an autism spectrum disorder research cohort by comparing BPA-response outcomes (Interested, Declined, Enrolled, Dismissed) in pediatric primary care practices (TCPs) serving diverse communities with those of subspecialty clinics. Compared to subspecialty clinics, TCPs had higher proportions of Interested responses for patients with private insurance (60.9% vs. 46.2%), Dismissed responses for patients with public insurance (30.1% vs. 20.0%), and Interested responses for non-white patients (47.7% vs. 33.3%). A targeted BPA can help researchers access more diverse groups and improve equitable representation. However, select groups more often had their alert dismissed, suggesting possible selection bias among some pediatricians regarding who should receive information about study opportunities.

Utilization of a Best Practice Alert (BPA) at Point-of-Care for Recruitment into a US-Based Autism Research Study.

Provider referral is one of the most influential factors in research recruitment. To ease referral burden on providers, we adapted the Best Practice Alert (BPA) in the EPIC Electronic Health Record and assessed its utility in recruiting pediatric patients with autism spectrum disorder for the national SPARK study. During a year-long surveillance, 1203 (64.0%) patients were Interested in SPARK and 223 enrolled. Another 754 participants not recruited via the BPA also enrolled; 35.5% of these participants completed their participation compared to 58.3% of BPA-referred participants. Results suggest that (a) a BPA can successfully engage providers in the study-referral process and (b) families who learn about research through their providers may be more engaged and effectively retained.

An initial trial of OPT-In-Early: An online training program for caregivers of autistic children.

LAY ABSTRACT: Early intervention can help children learn language and improve social communication. However, many barriers, including the expense of services and an insufficient number of providers, prohibit families from accessing services when their children are young. We developed a comprehensive online program for caregivers of autistic children. The program, Online Parent Training in Early Behavioral Intervention (OPT-In-Early), uses text and video demonstrations to teach caregivers effective methods for improving their children's language, social, and adaptive skills (e.g. using utensils, toilet training), and reducing their children's disruptive behavior. Sixty-three parents from three states participated in the study. Half of the parents received access to the OPT-In-Early program. After 4 months, parents who had access to the OPT-In-Early program learned more effective intervention strategies, and started using these strategies during interactions with their children, than parents who did not receive access to the program. Parent participation in OPT-In-Early did not significantly influence children's social communication compared to children whose parents did not have access to OPT-In-Early. A longer duration of parents using learned intervention skills with their children may be needed for children's social communication skills to improve.

Stepped-Care Cognitive Behavioral Therapy in Children on the Autism Spectrum with Co-occurring Anxiety.

This trial examined stepped-care cognitive-behavioral treatment (CBT) among 96 autistic youth with co-occurring anxiety. Step 1 included an open trial of parent-led, therapist-guided bibliotherapy. Step 2 was family-based CBT for those who did not respond to Step 1 or maintenance for those who did. Eighteen participants (28%) who completed Step 1 responded. Responders reported significantly lower pre-treatment anxiety, internalizing symptoms, and functional impairment than non-responders. After Steps 1 and 2, 80% of completers (55% intent-to-treat) were responders. Anxiety, impairment, and ASD-related impairments significantly improved. Youth in maintenance experienced faster improvement through post-treatment, though there were no group differences at 3-month-follow-up. A stepped approach may help some individuals in Step 1, particularly those who are less anxious.

Understanding Vaccine Hesitancy Among Parents of Children With Autism Spectrum Disorder and Parents of Children With Non-Autism Developmental Delays.

Parents of children with autism spectrum disorder (ASD) may be at greater risk for developing antivaccine beliefs that lead to vaccine delays and/or refusals for their children. We investigated current parental vaccine hesitancy, parents' beliefs about causes of children's developmental delays, and children's vaccination histories among parents of children with ASD or non-ASD developmental delays. Data were analyzed from 89/511 parents (17.4%) who completed the Parent Attitudes About Childhood Vaccines questionnaire and the Revised Illness Perception Questionnaire; 46.1% had childhood vaccination records available. Overall, 21/89 (23.6%, 95% confidence interval [CI]: 15.0-34.0) of parents were vaccine hesitant (ASD n = 19/21 [90.5%], non-ASD n = 2/21 [9.5%]). Parents of children with ASD were significantly more likely to agree with "toxins in vaccines" as a cause of their child's developmental delays (28.4% vs 5.0%, P = .034). The odds of being vaccine hesitant were 11.9 times (95% CI 2.9-48.0) greater among parents who agreed versus disagreed that toxins in vaccines caused their children's developmental delays. Rates of prior vaccine receipt did not differ between hesitant and nonhesitant groups.

A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.

OBJECTIVE: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships. METHODS: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing. RESULTS: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits. CONCLUSIONS: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.

Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18-73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwi-interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups-with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.

Parent-led, stepped-care cognitive-behavioral therapy for youth with autism and co-occurring anxiety: study rationale and method

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.

Person Ability Scores as an Alternative to Norm-Referenced Scores as Outcome Measures in Studies of Neurodevelopmental Disorders.

Although norm-referenced scores are essential to the identification of disability, they possess several features which affect their sensitivity to change. Norm-referenced scores often decrease over time among people with neurodevelopmental disorders who exhibit slower-than-average increases in ability. Further, the reliability of norm-referenced scores is lower at the tails of the distribution, resulting in floor effects and increased measurement error for people with neurodevelopmental disorders. In contrast, the person ability scores generated during the process of constructing a standardized test with item response theory are designed to assess change. We illustrate these limitations of norm-referenced scores, and relative advantages of ability scores, using data from studies of autism spectrum disorder and creatine transporter deficiency.

Evaluating Two Common Strategies for Research Participant Recruitment Into Autism Studies: Observational Study.

BACKGROUND: Ongoing research is necessary to better understand the causes of autism spectrum disorder (ASD), the developmental outcomes for individuals diagnosed with ASD, and the efficacy of the interventions. However, it is often difficult to recruit sufficient numbers of participants for studies, and despite the prevalence of ASD (currently estimated to affect 1 in 54 children), little research has focused on how to efficiently recruit participants with ASD. OBJECTIVE: The aim of this study was to determine the efficacy of two different paid advertisements-social media and radio advertising-in recruiting participants for a study enrolling people with ASD and their family members by examining the number of participants enrolled, the cost per participant, and the geographic reach of each type of advertising. METHODS: We examined participant enrollment in a study following nonoverlapping paid advertisements on a popular FM radio station (aired in three cities across two states) and Facebook (six advertisements that ran in five cities across two states). The total paid investment in the radio campaign was $12,030 and that in the Facebook campaign was $2950. Following the advertising campaigns, 1391 participants in the study who were affiliated with the Houston, Texas, site received email invitations to participate in a brief survey about the ways in which they learned about the study (eg, social media, medical provider, website) and which of these were most influential in their decisions to participate; 374 (26.8%) of the participants completed this survey. RESULTS: Social media advertising outperformed radio in all three parameters examined by enrolling more participants (338 vs 149), with a lower average cost per participant ($8.73 vs $80.74) and a wider geographic reach, based on a comparison of the number of zip codes within and outside of Texas for questionnaire respondents who rated social media as the most influential method of contact (n=367, χ21=5.85, P=.02). Of the 374 survey participants, 139 (37.2%) reported that they had seen the study on social media prior to enrollment, while only 9 (2.4%) said they heard about it via radio. CONCLUSIONS: Our findings suggest that advertising on social media can efficiently reach a large pool of potential participants with ASD, increasing the likelihood of meeting study enrollment goals. Researchers should consider allocating at least some portion of recruitment dollars to social media platforms as a means of quickly and inexpensively reaching out to their target populations, including for studies with in-person procedures.

Beliefs about causes of autism and vaccine hesitancy among parents of children with autism spectrum disorder.

Vaccine hesitancy may be more common among parents of children with autism spectrum disorder (ASD). We examined factors associated with ASD-specific vaccine hesitancy among caregivers of children with ASD who participated in the SPARK study (Simons Foundation Powering Autism Research for Knowledge). 225 participants completed an online survey containing the Parent Attitudes About Childhood Vaccines (PACV) questionnaire (measure of vaccine hesitancy) and the Illness Perception Questionnaire revised for parents of children with ASD (IPQ-R-ASD; measure of parents' views about ASD). 65 participants (28.8%) were vaccine hesitant (PACV score ≥ 50); children of vaccine-hesitant parents (VHPs) were less likely to be first born (n = 27, 41.5%), had greater ASD-symptom severity (mean Social Communication Questionnaire score = 23.9, SD = 6.9), and were more likely to have experienced developmental regression (n = 27, 50.9%) or plateau (n = 37, 69.8%). Compared to non-hesitant parents, VHPs significantly more often endorsed accident/injury, deterioration of the child's immune system, diet, environmental pollution, general stress, parents' negative views, parents' behaviors/decisions, parents' emotional state, and vaccines as causes for ASD. VHPs also had higher scores on the Personal Control, Treatment Control, Illness Coherence, and Emotional Representations subscales of the IPQ-R than did non-hesitant parents. In the final model, ASD-related vaccine hesitancy was significantly associated with higher scores on the Emotional Representations subscale (OR = 1.13, p = 0.10), agreement with deterioration of the child's immunity as a cause of ASD (OR = 12.47, p < 0.001), the child not having achieved fluent speech (OR = 2.67, p = 0.17), and the child experiencing a developmental plateau (OR = 3.89, p = 0.002). Findings suggest that a combination of child functioning and developmental history, as well as parents' negative views about and their sense of control over ASD, influence vaccine hesitancy among parents of children with ASD.

Language characterization in 16p11.2 deletion and duplication syndromes.

Expressive language impairment is one of the most frequently associated clinical features of 16p11.2 copy number variations (CNV). However, our understanding of the language profiles of individuals with 16p11.2 CNVs is still limited. This study builds upon previous work in the Simons Variation in Individuals Project (VIP, now known as Simons Searchlight), to characterize language abilities in 16p11.2 deletion and duplication carriers using comprehensive assessments. Participants included 110 clinically ascertained children and family members (i.e., siblings and cousins) with 16p11.2 BP4-BP5 deletion and 58 with 16p11.2 BP4-BP5 duplication between the ages of 2-23 years, most of whom were verbal. Regression analyses were performed to quantify variation in language abilities in the presence of the 16p11.2 deletion and duplication, both with and without autism spectrum disorder (ASD) and cognitive deficit. Difficulties in pragmatic skills were equally prevalent in verbal individuals in both deletion and duplication groups. NVIQ had moderate quantifiable effects on language scores in syntax and semantics/pragmatics (a decrease of less than 1 SD) for both groups. Overall, language impairments persisted even after controlling for ASD diagnosis and cognitive deficit. Language impairment is one of the core clinical features of individuals with 16p11.2 CNVs even in the absence of ASD and cognitive deficit. Results highlight the need for more comprehensive and rigorous assessment of language impairments to maximize outcomes in carriers of 16p11.2 CNVs.

Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers.

Individuals with 16p11.2 copy number variant (CNV) show considerable phenotypic heterogeneity. Although autism spectrum disorder (ASD) is reported in approximately 20-23% of individuals with 16p11.2 CNVs, ASD-associated symptoms are observed in those without a clinical ASD diagnosis. Previous work has shown that genetic variation and prenatal and perinatal birth complications influence ASD risk and symptom severity. This study examined the impact of genetic and environmental risk factors on phenotypic heterogeneity among 16p11.2 CNV carriers. Participants included individuals with a 16p11.2 deletion (N = 96) or duplication (N = 77) with exome sequencing from the Simons VIP study. The presence of prenatal factors, perinatal events, additional genetic events, and gender was studied. Regression analyses examined the contribution of each risk factor on ASD symptomatology, cognitive functioning, and adaptive abilities. For deletion carriers, perinatal and additional genetic events were associated with increased ASD symptomatology and decrements in cognitive and adaptive functioning. For duplication carriers, secondary genetic events were associated with greater cognitive impairments. Being female sex was a protective factor for both deletion and duplication carriers. Our findings suggest that ASD-associated risk factors contribute to the variability in symptom presentation in individuals with 16p11.2 CNVs. LAY SUMMARY: There are a wide range of autism spectrum disorder (ASD) symptoms and abilities observed for individuals with genetic changes of the 16p11.2 region. Here, we found perinatal complications contributed to more severe ASD symptoms (deletion carriers) and additional genetic mutations contributed to decreased cognitive abilities (deletion and duplication carriers). A potential protective factor was also observed for females with 16p11.2 variations. Autism Res 2020, 13: 1300-1310. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Parent-led, stepped-care cognitive-behavioral therapy for youth with autism and co-occurring anxiety: study rationale and method.

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.