Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology.

Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters. Twenty (61%) participants received an ID diagnosis, and 12 of the 31 (39%) who were fully evaluated received the diagnosis of ASD. A diagnosis of ID, lower full-scale IQ (sample mean = 65 ± 26), and lower adaptive behavior composite scores (sample mean = 67 ± 23) were associated with several biomarkers. Higher concentrations of plasma propionylcarnitine, plasma total 2-methylcitrate, serum erythropoietin, and mitochondrial biomarkers plasma FGF21 and GDF15 were associated with a more severe ID profile. Reduced 1-13C-propionate oxidative capacity and decreased levels of plasma and urinary glutamine were also associated with a more severe ID profile. Only two parameters, increased serum erythropoietin and decreased plasma glutamine, were associated with ASD. Plasma glycine, one of the defining features of PA, was not meaningfully associated with either ID or ASD. Thus, while both ID and ASD were commonly observed in our PA cohort, only ID was robustly associated with metabolic parameters. Our results suggest that disease severity and associated mitochondrial dysfunction may play a role in CNS complications of PA and identify potential biomarkers and candidate surrogate endpoints.

Psychometric Assessment of the Eyberg Child Behavior Inventory in Children with Autism in Community Settings.

The Eyberg Child Behavior Inventory (ECBI) is a frequently used measure to assess interfering behaviors in children and psychometric properties have recently been examined in children with autism spectrum disorder (ASD). There is a need to confirm the identified factors and examine the factor structure in a racially/ethnically diverse, community-based sample. The current study conducts a psychometric analysis of the ECBI in a sample of children with ASD receiving publicly-funded mental health services. Data were collected from 201 children with ASD ages 5-13 years (60% Hispanic/Latinx) participating in a community effectiveness trial. Confirmatory factor analysis indicated poor model fit using previously identified factors and a new four-factor solution was identified. Clinical and research implications of these findings are discussed.

NIH Toolbox Cognition Battery Feasibility in Individuals With Williams Syndrome.

The NIH Toolbox Cognition Battery (NIHTB-CB) was developed for epidemiological and longitudinal studies across a wide age span. Such a tool may be useful for intervention trials in conditions characterized by intellectual disability (ID), such as Williams syndrome (WS). Three NIHTB-CB tasks, including two executive functioning (Flanker, Dimensional Change Card Sort) and one episodic memory (Picture Sequence Memory) task, were given to 47 individuals with WS, ages 4 to 50, to evaluate feasibility (i.e., proportion of valid administrations) in this population. Findings indicated that NIHTB-CB tests showed good feasibility. Flanker and DCCS age-corrected scores were negatively correlated with age and showed floor effects, indicating these scores may not be useful for quantifying performance on these NIHTB-CB tests in ID.

Training Community Therapists in AIM HI: Individual Family and Neighborhood Factors and Child/Caregiver Outcomes.

OBJECTIVE: Publicly funded mental health services play an important role in caring for children with mental health needs, including children with autism spectrum disorder (ASD). This study assessed the associations between individual family- and neighborhood-level sociodemographic factors and baseline family functioning and long-term outcomes when community therapists were trained to deliver An Individualized Mental Health Intervention for ASD (AIM HI). METHOD: Participants included 144 children with ASD (ages 5 to 13 years; 58.3% Latinx) and their caregivers whose therapists received AIM HI training within a cluster-randomized effectiveness-implementation trial in publicly funded mental health services. Sociodemographic strain (e.g., low income, less education, single-parent status, minoritized status) was coded at the individual family and neighborhood level, and caregivers rated caregiver strain at baseline. Child interfering behaviors and caregiver sense of competence were assessed at baseline and 6-, 12- and 18-months after baseline. RESULTS: Higher caregiver strain was associated with higher intensity of child behaviors (B = 5.17, p < .001) and lower caregiver sense of competence (B = -6.59, p < 001) at baseline. Child and caregiver outcomes improved over time. Higher caregiver strain (B = 1.50, p < .001) and lower family sociodemographic strain (B = -0.58, p < .01) were associated with less improvements in child behaviors. Lower caregiver strain (B = -2.08, p < .001) and lower neighborhood sociodemographic strain (B = -0.51, p < .01) were associated with greater improvements in caregiver sense of competence. CONCLUSIONS: Findings corroborate the importance of considering both family and neighborhood context in the community delivery of child-focused EBIs. TRIAL REGISTRATION: Clinical Trials NCT02416323.

The effectiveness of training community mental health therapists in an evidence-based intervention for ASD: Findings from a hybrid effectiveness-implementation trial in outpatient and school-based mental health services.

LAY ABSTRACT: Publicly funded mental health services play an important role in caring for school-age children with autism spectrum disorder (ASD); however, therapists report a lack of specialized ASD training, which families identity as a barrier in obtaining mental health services for their children. An Individualized Mental Health Intervention for ASD (AIM HI) was developed in collaboration with community stakeholders to respond to identified needs of children and community therapists. The current study examined the effects of therapist training in AIM HI on the changes in therapist practice, including therapists' use of evidence-based intervention strategies in session. Data were collected from a study conducted in community outpatient and school based mental health programs randomly assigned to receive AIM HI therapist training or observation of routine care. Therapist and child clients were enrolled from participating programs. Therapists in AIM HI training received training and consultation for 6 months while delivering the AIM HI intervention to a participating client; therapists in usual care delivered routine care. Both groups of therapists video recorded psychotherapy sessions which were scored by trained raters. Differences between training groups were examined using multilevel modeling. Therapists trained in AIM HI were observed to use more extensive active teaching strategies with caregivers, engagement strategies with children, strategies promoting continuity of care, and had more structured sessions with more effective pursuit of caregiver and children skill teaching. Therapist licensure moderated some training outcomes.

Psychotropic Medication Use by Children with Autism Served in Publicly Funded Mental Health Settings.

OBJECTIVE: The aim of this study was to characterize patterns of and factors associated with psychotropic medication use in children with autism spectrum disorder (ASD) receiving publicly funded mental health services. METHOD: Data were extracted from 202 children with ASD participating in a cluster randomized trial of An Individualized Mental Health Intervention for ASD conducted in 29 publicly funded mental health programs. Children with ASD were aged 5 to 13 years (M = 9.1 years, SD = 2.4), and were 84.2% male and 59.9% Latinx. Child ASD and cognitive functioning were determined by standardized assessment. Caregivers reported child psychotropic medication use, behavior problems, ASD symptom severity, mental health symptoms, family demographics, and caregiver strain at the baseline. RESULTS: Nearly half (49.5%) of participants used psychotropic medication(s) within the past 6 months, with stimulants being most commonly reported. Child co-occurring attention-deficit/hyperactivity disorder (ADHD) (B = 1.55, p < 0.01; 95% confidence interval [CI]: 0.53-2.57), lower cognitive functioning (B = -0.03, p = 0.02; 95% CI: -0.05 to <0.00), and non-Hispanic White ethnicity (vs Hispanic/Latinx; B = 1.02, p = 02; 95% CI: -1.89 to -0.14) were associated with a greater likelihood of using any type of medication. Factors associated with medication use varied by class: stimulants-ADHD, lower ASD symptom severity, and more intensive behavior problems; SSRIs-higher ASD symptom severity; alpha-2 agonists-ADHD, higher ASD symptom severity, lower cognitive functioning, and higher caregiver strain; and antipsychotics-none. CONCLUSION: The findings highlight factors associated with psychotropic medication use for a clinically complex population, which may inform community care improvement efforts.

Impact of Therapist Training on Parent Attendance in Mental Health Services for Children with ASD.

OBJECTIVE: The current study explored the impact of training therapists in a mental health intervention for children with autism spectrum disorder (ASD) on parent attendance in their children's therapy sessions. We also examined family, therapist, and program factors as potential moderators. METHOD: Data were drawn from a cluster-randomized community effectiveness trial of "An Individualized Mental Health Intervention for ASD (AIM HI)". Participants included 168 therapists yoked with 189 children recruited from publicly-funded mental health services. Data included family (caregiver strain, parent sense of competence, race/ethnicity), therapist (background, experience), and program (service setting) characteristics, and parent session attendance. Multilevel models were used to evaluate the effectiveness of AIM HI therapist training on caregiver attendance and identify moderators of training effects on parent attendance. RESULTS: Parents attended a higher percentage of sessions in the AIM HI training condition compared to the Usual Care condition. Program service setting moderated the effect of AIM HI training, with higher parent attendance in non-school (mostly outpatient) settings compared to school settings and a significantly smaller difference between the settings in the AIM HI condition. CONCLUSIONS: Effective strategies to promote parent engagement, especially in service settings such as schools, are warranted. Findings support the effectiveness of AIM HI training in promoting parent attendance across multiple publicly-funded mental health service settings. The larger effect in school-based programs supports the utility of training in evidence-based interventions such as AIM HI to increase the feasibility of parent attendance in such services.

Use of the Vineland-3, a measure of adaptive functioning, in CLN3.

Progressive vision loss and neurocognitive impairment are early and frequent presentations in CLN3 disease. This highlights neurodevelopmental functioning as critical to the disease, but limits the neuropsychological test repertoire. We evaluated the convergent validity of the Vineland Adaptive Behavior Scales as a potential outcome measure. In a prospective observational study of 22 individuals (female:male 11:11; 6-20 years-old) with a molecular diagnosis of CLN3, we used generalized linear models and Spearman correlations to quantify the relationship of the adaptive behavior composite (ABC) standard score with established outcomes of verbal IQ (VIQ) and disease severity (Unified Batten Disease Rating Scale, UBDRS) scores. We analyzed ABC changes in 1-year follow-up data in a subset of the same cohort (n = 17). The ABC and VIQ, both standard scores, exhibited a strong positive correlation in cross-sectional data (r = 0.81). ABC and UBDRS scores were strongly and positively correlated in cross-sectional data (rrange  = 0.87-0.93). Participants' ABC scores decreased slightly over the 1-year follow-up period (mean change, 95% CI: -5.23, -2.16). The convergent validity of the Vineland-3 for use in CLN3 is supported by its relationships with the established outcomes of VIQ and UBDRS. Future longitudinal research, including replication in other cohorts and evaluation of sensitivity to change, will be important to establish utility of the Vineland-3 for monitoring change in CLN3.

Severity modeling of propionic acidemia using clinical and laboratory biomarkers.

PURPOSE: To conduct a proof-of-principle study to identify subtypes of propionic acidemia (PA) and associated biomarkers. METHODS: Data from a clinically diverse PA patient population ( https://clinicaltrials.gov/ct2/show/NCT02890342 ) were used to train and test machine learning models, identify PA-relevant biomarkers, and perform validation analysis using data from liver-transplanted participants. k-Means clustering was used to test for the existence of PA subtypes. Expert knowledge was used to define PA subtypes (mild and severe). Given expert classification, supervised machine learning (support vector machine with a polynomial kernel, svmPoly) performed dimensional reduction to define relevant features of each PA subtype. RESULTS: Forty participants enrolled in the study; five underwent liver transplant. Analysis with k-means clustering indicated that several PA subtypes may exist on the biochemical continuum. The conventional PA biomarkers, plasma total 2-methylctirate and propionylcarnitine, were not statistically significantly different between nontransplanted and transplanted participants motivating us to search for other biomarkers. Unbiased dimensional reduction using svmPoly revealed that plasma transthyretin, alanine:serine ratio, GDF15, FGF21, and in vivo 1-13C-propionate oxidation, play roles in defining PA subtypes. CONCLUSION: Support vector machine prioritized biomarkers that helped classify propionic acidemia patients according to severity subtypes, with important ramifications for future clinical trials and management of PA.

Characterizing therapist delivery of evidence-based intervention strategies in publicly funded mental health services for children with autism spectrum disorder: Differentiating practice patterns in usual care and AIM HI delivery.

LAY ABSTRACT: This study was conducted to identify patterns of therapist delivery of evidence-based intervention strategies with children with autism spectrum disorder receiving publicly funded mental health services and compare strategy use for therapists delivering usual care to those trained to deliver AIM HI ("An Individualized Mental Health Intervention for ASD"), an intervention designed to reduce challenging behaviors in children with autism spectrum disorder. For therapists trained in AIM HI, intervention strategies grouped onto two factors, Autism Engagement Strategies and Active Teaching Strategies, while strategies used by usual care therapists grouped onto a broader single factor, General Strategies. Among usual care therapists, General Strategies were related to an increase in child behavior problems, whereas for AIM HI therapists, Active Teaching Strategies were related with reductions in child behavior problems over 18 months. Findings support the use of active teaching strategies in reducing challenging behaviors in children with autism spectrum disorder and provide support for the effectiveness of training therapists in evidence-based interventions to promote the delivery of targeted, specific intervention strategies to children with autism spectrum disorder in mental health services.

Training Community Therapists to Deliver an Individualized Mental Health Intervention for Autism Spectrum Disorder: Changes in Caregiver Outcomes and Mediating Role on Child Outcomes.

OBJECTIVE: This study examines the impact of training therapists to deliver "An Individualized Mental Health Intervention for Autism Spectrum Disorder (ASD)" (AIM HI) for children with autism spectrum disorder on caregiver outcomes and the mediating role of changes in caregiver outcomes on child outcomes. METHOD: Data were drawn from a cluster randomized trial conducted in 29 publicly funded mental health programs randomized to receive AIM HI training or usual care. Therapists were recruited from enrolled programs and child/caregiver participants enrolled from therapists' caseloads. Participants included 202 caregivers of children 5 to 13 years of age with autism spectrum disorder. Caregiver strain and sense of competence were assessed at baseline and 6 month postbaseline. Child behaviors were assessed at baseline and 6, 12, and 18 months postbaseline. Therapist delivery of evidence-based intervention strategies were assessed between baseline and 6 months. RESULTS: A significant training effect was observed for caregiver sense of competence, with AIM HI caregivers reporting significantly greater improvement relative to usual care. There was no significant training effect for caregiver strain. Observer-rated therapist delivery of evidence-based interventions strategies over 6 months mediated training effects for sense of competence at 6 months. Changes in sense of competence from baseline to 6 months was associated with reduced child challenging behaviors at 6 months and mediated child outcomes at 12 and 18 months. CONCLUSION: Combined with research demonstrating effectiveness of therapist AIM HI training on child outcomes, this study provides further evidence of the positive impact of training community therapists in the AIM HI intervention. CLINICAL TRIAL REGISTRATION INFORMATION: Effectiveness and Implementation of a Mental Health Intervention for ASD (AIM HI); https://clinicaltrials.gov/; NCT02416323.

Chromoanasynthesis as a cause of Jacobsen syndrome.

Jacobsen syndrome (MIM #147791) is a rare multisystem genomic disorder involving craniofacial abnormalities, intellectual disability, other neurodevelopmental defects, and terminal truncation of chromosome 11q, typically deleting ~170 to >340 genes. We describe the first case of Jacobsen syndrome caused by congenital chromoanasynthesis, an extreme form of complex chromosomal rearrangement. Six duplications and five deletions occurred on one copy of chromosome 11q with microhomology signatures in the breakpoint junctions, indicating an all-at-once replication-based rearrangement mechanism in a gametocyte or early post-zygotic cell. Eighteen genes were deleted from the Jacobsen region, including KIRREL3, which is associated with intellectual disability.

Neurodevelopmental Characterization of Young Children Diagnosed with Niemann-Pick Disease, Type C1.

OBJECTIVE: Niemann-Pick disease type C1 (NPC1) is a lysosomal storage disease characterized by progressive neurodegeneration, with the age of diagnosis ranging from the prenatal period through adulthood. Although neurological symptoms usually precede genetic diagnosis, they do not necessarily prompt diagnosis in the early years. Few prospective data are available to describe neurological onset, including neurodevelopmental delays, in children with NPC1. This dearth of information hinders the planning and implementation of adequate monitoring and treatment for the neurodevelopmental sequelae of NPC1. METHOD: Twenty-nine infants, toddlers, and preschoolers younger than 6 years participated in a natural history study and were administered neurodevelopmental assessments using instruments commonly used for early intervention screening in the community. RESULTS: Twenty-two of 29 participants met the criteria for a significant delay of at least 1.5 SDs below the mean in at least one domain of development; the youngest children often met these criteria for a significant delay based on motor delays, but cognitive and language delays were also common. However, only 11 of the 22 participants were reported to receive early intervention services before study entry. CONCLUSION: Although neurological symptoms may not prompt the genetic diagnosis of NPC1, the current findings support the use of a multimethod approach to repeated assessments for young children with the diagnosis because of the frequency of developmental delays or decline in multiple domains. The diagnosis of NPC1 alone should qualify children for evaluation for early intervention services and consideration of investigational therapeutic interventions.

Emergent life events in the delivery of a caregiver-mediated evidence-based intervention for children with autism spectrum disorder in publicly funded mental health services.

LAY ABSTRACT: Mental health clinicians often report significant challenges when delivering evidence-based interventions (EBI) in community settings, particularly when unexpected client stressors (or emergent life events; ELEs) interfere with the therapy process. The current study sought to extend the study of ELEs to children with Autism Spectrum Disorder (ASD) by examining the occurrence and impact of ELEs in the context of a collaborative, caregiver-mediated intervention for reducing challenging behaviors in children with ASD. This intervention was An Individualized Mental Health Intervention for children with ASD (referred to as AIM HI). Participants included 38 clinicians and child clients who were enrolled in a community effectiveness trial of AIM HI. Video recordings of 100 therapy sessions were coded for caregiver-reported ELEs and also how well clinicians adhered to the AIM HI protocol. Results indicated that mild to severe ELEs were reported in 36% of therapy sessions, and were reported for 58% of children at some point during the intervention. Children who had a greater number of diagnoses (in addition to the autism diagnosis) tended to have more ELEs. In addition, clinicians with less years of experience tended to have sessions with more ELEs. There was no significant link between ELEs and how well clinicians adhered to the AIM HI protocol. Findings offer implications for the implementation of EBI, particularly the importance of incorporating clinician training in addressing complex presentations and crises in the context of EBIs.

Characterizing Shared and Unique Implementation Influences in Two Community Services Systems for Autism: Applying the EPIS Framework to Two Large-Scale Autism Intervention Community Effectiveness Trials.

The purpose of this study was to examine common and unique factors influencing implementation process for two evidence-based interventions for children with autism spectrum disorder (ASD) in mental health and education service contexts. This study prospectively collected qualitative data from intervention developers and research staff on the implementation process within the context of two separate ASD intervention effectiveness trials. Results reveal common and unique factors influencing implementation in both study contexts. Implementation leadership and provider attitudes and motivation emerge as key influences on implementation across systems. These findings provide promising targets for modular implementation interventions that can be leveraged within growing, large-scale translation efforts in usual care.

Using stakeholder perspectives to guide systematic adaptation of an autism mental health intervention for Latinx families: A qualitative study.

Embedded within a Hybrid Type 1 randomized effectiveness-implementation trial in publicly funded mental health services, the current study identified stakeholder recommendations to inform cultural adaptations to An Individualized Mental Health Intervention for Autism Spectrum Disorder (AIM HI) for Latinx and Spanish-speaking families. Recommendations were collected through focus groups with therapists (n = 17) and semi-structured interviews with Latinx parents (n = 29). Relevant themes were identified through a rapid assessment analysis process and thematic coding of interviews. Adaptations were classified according to the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) to facilitate fit, acceptability, and sustained implementation of AIM HI and classify the content, nature, and goals of the adaptations. Recommended adaptations were classified through FRAME as tailoring training and intervention materials, changing packaging or materials, extending intervention pacing, and integrating supplemental training strategies. Goals for adaptations included improving fit for stakeholders, increasing parent engagement, and enhancing intervention effectiveness. The current study illustrates the process of embedding an iterative process of intervention adaptation within a hybrid effectiveness-implementation trial. The next steps in this study are to integrate findings with implementation process data from the parent trial to develop a cultural enhancement to AIM HI and test the enhancement in a Hybrid Type 3 implementation-effectiveness trial.

In-Session Caregiver Behaviors during Evidence-Based Intervention Delivery for Children with ASD in Community Mental Health Services.

An Individualized Mental Health Intervention for ASD, ("AIM HI"), is a collaborative, caregiver-mediated and child-directed intervention for reducing challenging behaviors in children with autism spectrum disorder developed for delivery in community mental health programs. Using observational data from AIM HI sessions, the present study characterized the occurrence of two types of in-session caregiver behaviors: expressed concerns (i.e., expressing concerns about treatment strategies; expressing difficulty using skills; expressing difficulty completing homework) and participation engagement (i.e., asking questions; participating in session activities; showing commitment to therapy). Further analyses examined cultural differences in caregiver behaviors and associations between caregiver behaviors and clinician adherence. Participants included 39 caregiver-clinician dyads enrolled in a community effectiveness trial of AIM HI. Video recordings from 107 sessions during the first two months of treatment were coded for in-session caregiver behaviors and clinician adherence. Results indicated that expressed concerns were observed in 47% of sessions. When controlling for household income, Latinx caregivers were rated lower for expressing concerns about treatment strategies and demonstrated lower participation engagement behaviors in session compared with non-Latinx White caregivers, suggesting that cultural factors may impact verbal engagement in sessions. Finally, expressing concerns about treatment strategies, expressing difficulty using skills, and participation engagement were positively associated with clinician adherence. Findings suggest that some expressed concerns and participation engagement behaviors may be indicators of positive caregiver engagement in the context of a collaborative intervention, and lower levels of such caregiver engagement may actually impede clinicians' delivery of intensive evidence-based intervention in routine care.

Effectiveness of Training Therapists to Deliver An Individualized Mental Health Intervention for Children With ASD in Publicly Funded Mental Health Services: A Cluster Randomized Clinical Trial.

Importance: Publicly funded mental health services play an important role in addressing co-occurring mental health problems in children with autism spectrum disorder (ASD); however, therapists report lacking training to effectively serve this complex population. Objective: To test the effectiveness of training community therapists in An Individualized Mental Health Intervention for ASD (AIM HI) on challenging behaviors across 18 months among children with ASD and identify moderators and mediators of any intervention effects. Design, Setting, and Participants: Cluster randomized trial conducted in 29 publicly funded outpatient and school-based mental health programs in southern California from 2012 to 2017. Programs were randomized to receive immediate AIM HI training or provide usual care followed by receipt of AIM HI training. Therapist participants were recruited from enrolled programs, and child participants were recruited from participant therapists' caseloads. Data were analyzed from 202 children with ASD who were aged 5 to 13 years. Interventions: The AIM HI protocol is a package of parent-mediated and child-focused strategies aimed to reduce challenging behaviors in children with ASD who are 5 to 13 years old. It was designed for delivery in publicly funded mental health services based on a systematic assessment of therapist training needs and child clinical needs. The therapist training and consultation process takes approximately 6 months and includes an introductory workshop, 11 structured consultation meetings as the therapist delivers AIM HI with a current client, and case-specific performance feedback from trainers. Main Outcomes and Measures: Child participants were assessed for challenging behaviors using the Eyberg Child Behavior Inventory (ECBI) and Social Skills Improvement System (SSIS) Competing Problem Behaviors scales based on parent report at baseline and at 6-month intervals for 18 months. Outcomes were analyzed using intent-to-treat models. Results: In total, 202 children with ASD (mean [SD] age, 9.1 [2.4] years; 170 [84.2%] male; 121 [59.9%] Latinx) were eligible, enrolled, and included in the analyses. Statistically significant group by time interactions for the ECBI Intensity (B = -0.38; P = .02) and ECBI Problem (B = -1.00; P = .005) scales were observed, with significantly larger decreases in ECBI Intensity scores in the AIM HI group (B = -1.36; P < .001) relative to the usual care group (B = -0.98; P < .001) and a significantly larger decrease in ECBI Problem scores in the AIM HI group (B = -1.22; P < .001) relative to the usual care group (B = -0.20; P = .29). Therapist fidelity moderated these intervention effects. Conclusions and Relevance: The present findings support the effectiveness of training therapists to deliver the AIM HI model to children with ASD receiving publicly funded mental health services. Trial Registration: ClinicalTrials.gov identifier: NCT02416323.

Therapists' Adaptations to an Intervention to Reduce Challenging Behaviors in Children with Autism Spectrum Disorder in Publicly Funded Mental Health Services.

Publicly funded mental health services play an important role in serving children with autism spectrum disorder (ASD). Previous research indicates a high likelihood of adaptations when therapists deliver evidence based practices to non-ASD populations, though less is known about therapists' use of adaptations for children with ASD receiving mental health services. The current study uses a mixed quantitative and qualitative approach to characterize the types and reasons therapists adapted a clinical intervention [An Individualized Mental Health Intervention for Children with ASD (AIM HI)] for delivery with clinically complex children with ASD served in publicly funded mental health settings and identify therapist characteristics that predict use of adaptations. The most common adaptations were characterized as augmenting AIM HI and were done to individualize the intervention to fit with therapeutic style, increase caregiver participation, and address clients' and caregivers' needs and functioning. No therapist characteristics emerged as significant predictors of adaptations. Results suggest that therapists' adaptations were largely consistent with the AIM HI protocol while individualizing the model to address the complex needs of youth with ASD.