In vivo translocator protein in females with autism spectrum disorder: a pilot study.

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET-MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

Clinical Challenges and Solutions in Adapting Cognitive Behavioral Therapy for Anxiety in Adults With Intellectual Disability.

While cognitive behavioral therapy (CBT) is a first-line treatment for anxiety, it is not typically offered to those with intellectual disability (ID). In this article, we provide a historical perspective on the treatment of mental health concerns in adults with ID, describe an adapted CBT treatment for anxiety in adults with Williams syndrome (WS) and mild to moderate ID, and discuss general modifications to CBT for adults with ID. Strategies used to successfully adapt CBT for adults with WS that may generalize for adults with ID more broadly include: (a) using child-based CBT manuals as a framework; (b) involving a caregiver as a therapy partner; (c) incorporating a high level of repetition; (d) simplifying language; (e) slowing the pace of instruction; and (f) incorporating specific examples and adaptations for WS.

A Manualized Behavioral Therapy Intervention for Youth with Autism Spectrum Disorder and Substance Use Disorder.

Research highlights the increasing overlap of autism spectrum disorder and substance use disorders in young people. However, no behavioral treatments exist addressing this comorbidity despite great need. A team of clinicians developed an integrated behavioral protocol addressing substance use in youth with autism spectrum disorder. The multidisciplinary team developed 12 youth, 7 parent, and 3 joint modules based on established evidence-based therapies shown to have effectiveness separately addressing autism spectrum and substance use. Two cases are discussed to illuminate this integrated intervention. Adaptations to the protocol were made during feedback from patients and their parents. Further research is needed to determine the effectiveness of this preliminary protocol.

Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder.

Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. LAY SUMMARY: Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment.

Parent Description of Anxiety in Angelman Syndrome.

Anxiety is being increasingly identified in Angelman syndrome (AS). Qualitative questions and quantitative assessments were used to evaluate for anxiety in 50 subjects with AS. In-person evaluations assessed behaviors concerning for anxiety and circumstances wherein they occurred. Caregivers completed anxiety and other behavioral rating scales. Caregiver responses were categorized and compared to items from anxiety rating scales. The most common behavioral manifestation of anxiety was "aggression." The most common circumstance was "separation from caregiver/parent." Subjects had elevated scores on anxiety, irritability and hyperactivity scales with lower mean scores among subjects with a maternal deletion. The Pediatric Anxiety Rating Scale best captured behaviors described by caregivers. Existing anxiety scales should be adapted for use in AS.

Facilitator Reflections on Shared Expertise and Adaptive Leadership in ECHO Autism: Center Engagement.

INTRODUCTION: Project Extension for Community Healthcare Outcomes (ECHO) is used to increase provider capacity in a wide range of health care specialties. ECHO Autism: Center Engagement is a program that promotes improvement in autism care by improving the management of autism care centers. The program's focus brought experienced clinicians together as both facilitators and participants in an ECHO series. ECHO Autism: Center Engagement facilitators devised a reflective writing exercise to prospectively study their experience leading this new curriculum. METHODS: Drawing on a qualitative thematic analysis of longitudinal reflective writing exercises from seven "Hub Team" facilitators, we describe how ECHO leaders cultivate a learning environment that emphasizes shared learning and acknowledges the expertise of ECHO participants. RESULTS: The analysis generated three main themes: (1) Hub Team facilitators valued reciprocal exchange with Spoke sites, a theme we name "shared learning," (2) Hub Team facilitators demonstrated high levels of awareness about their facilitation styles, and (3) Hub Team facilitators cultivated an interactional style they described as "all teach, all learn." DISCUSSION: Examining the experiences of ECHO facilitators produces qualitative accounts of continuing professional development that may not be captured in other program evaluation approaches. In the case of ECHO Autism: Center Engagement, facilitators cultivated an environment of shared learning, which acknowledged the expertise of both facilitators and participants. These findings are pertinent for scholars of continuing education in health professions who lead educational programs where participants and facilitators have high levels of overlap in their areas of expertise and years of experience.

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Psychiatric Assessment of Social Impairment Across the Lifespan.

Although autism spectrum disorder (ASD) is the prototypical psychiatric disorder of social impairment, several if not most psychiatric disorders are characterized by prominent impairments in social functioning. A challenge in clinically assessing and describing social impairment is that it has been variably defined and can be difficult to measure. In this article we consider the psychiatric differential diagnosis of social impairment within the DSM-5 framework. We describe the features of social impairment in 13 DSM-5 disorders from a developmental perspective and highlight diagnostic factors that differentiate among the disorders, including the main features of social impairment, verbal communication, nonverbal communication, course of social impairment, social cognition, and key features of accompanying neuropsychiatric symptoms. We conclude by describing an approach for assessing social impairment across the lifespan.

Families' Experiences With Family Navigation Services in the Autism Treatment Network.

BACKGROUND AND OBJECTIVES: Families of children with autism spectrum disorder (ASD) often experience challenges navigating multiple systems to access services. Family navigation (FN) is a model to provide information and support to access appropriate services. Few studies have been used to examine FN's effectiveness for families of children with ASD. This study used mixed methods to (1) characterize FN services received by a sample of families in the Autism Treatment Network; (2) examine change in parent-reported activation, family functioning, and caregiver strain; and (3) explore families' experiences with FN services. METHODS: Family characteristics and parent outcomes including parent activation, family functioning, and caregiver strain were collected from 260 parents in the Autism Treatment Network. Descriptive statistics and linear mixed models were used for aims 1 and 2. A subsample of 27 families were interviewed about their experiences with FN services to address aim 3. RESULTS: Quantitative results for aims 1 and 2 revealed variability in FN services and improvement in parent activation and caregiver strain. Qualitative results revealed variability in family experiences on the basis of FN implementation differences (ie, how families were introduced to FN, service type, intensity, and timing) and whether they perceived improved skills and access to resources. CONCLUSIONS: Findings suggest FN adaptations occur across different health care delivery systems and may result in highly variable initial outcomes and family experiences. Timing of FN services and case management receipt may contribute to this variability for families of children with ASD.

Assessment of speech and fine motor coordination in children with autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by difficulty in communication, which includes a high incidence of speech production errors. We hypothesize that these errors are partly due to underlying deficits in motor coordination and control, which are also manifested in degraded fine motor control of facial expressions and purposeful hand movements. In this pilot study, we computed correlations of acoustic, video, and handwriting time-series derived from five children with ASD and five children with neurotypical development during speech and handwriting tasks. These correlations and eigenvalues derived from the correlations act as a proxy for motor coordination across articulatory, laryngeal, and respiratory speech production systems and for fine motor skills. We utilized features derived from these correlations to discriminate between children with and without ASD. Eigenvalues derived from these correlations highlighted differences in complexity of coordination across speech subsystems and during handwriting, and helped discriminate between the two subject groups. These results suggest differences in coupling within speech production and fine motor skill systems in children with ASD. Our long-term goal is to create a platform assessing motor coordination in children with ASD in order to track progress from speech and motor interventions administered by clinicians.

Considerations for Treating Young People With Comorbid Autism Spectrum Disorder and Substance Use Disorder.

Although substance use disorder (SUD) and autism spectrum disorder (ASD) are highly comorbid with other mental disorders and commonly have onset during childhood,1 little attention has been paid to their overlap. Despite limited data suggesting that up to 4% of patients with ASD also have substance-related problems,2 there are no existing guidelines, protocols, or tailored resources focused on SUD in young people with co-occurring ASD. This is concerning given that the simultaneous presence of these disorders presents unique challenges that complicate clinical care. In particular, many of the symptoms of ASD can interfere with standard SUD treatment. Thus, when treating patients with this comorbidity, practitioners should consider the following: communication difficulties, diminished capacity for motivation and insight, limited social interactions, and obstacles to treatment engagement.

Buspirone for the treatment of anxiety-related symptoms in Angelman syndrome: a case series.

OBJECTIVES: Angelman syndrome (AS) is a neurogenetic disorder associated with impaired expression of the ubiquitin-protein ligase E3A gene on chromosome 15. AS results in intellectual disability with limited expressive language, epilepsy, ataxia, sleep impairment, and problematic behavior which may include anxiety. Buspirone is a serotonin (5-HT)1A receptor partial agonist used in the treatment of anxiety disorders and may, therefore, have a treatment role for patients with AS. METHODS: We describe three patients who were given open-label buspirone for the treatment of behaviors thought to be related to anxiety. RESULTS: We found significant improvement in symptoms of anxiety with buspirone. Patients tolerated long-term usage of the medication. CONCLUSION: The findings of this study suggest that buspirone may be effective for the amelioration of behaviors related to anxiety in patients with AS, and well tolerated. Limitations include the open-label nature of these treatments, the small sample size and the absence of a control group.

Exploring the use of Sidekicks! For children with autism spectrum disorder (ASD).

Clinicians and educators are increasingly using technology within the context of existing therapies and teaching methodologies. The growing use of mobile clinical tools is particularly exciting for individuals with autism spectrum disorder (ASD), as technologically based interventions have been shown to be both efficacious (to target academics, adaptive behavior, disruptive behavior, etc.) and accepted in this population (Odom et al., 2015). In addition, these tools have the potential to address two significant impediments in ASD intervention, the anxiety and/or skill deficits often associated with face-to-face interactions and skill generalization outside of the therapy office (Wieckowski & White, 2017). In other words, the use of technology may serve as an important preliminary or prerequisite step for face-to-face therapeutic progress. The purpose of this paper is to present a new, interactive clinical app that explicitly utilizes an individual's restricted interests to teach skills and improve communication. The paper will briefly review the ways in which individuals with ASD may be good candidates for technological-based interventions, explore the current role of technology in existing evidence-based therapies, and discuss the use of a new technology, Sidekicks!, that has been developed for this population. A case example will then illustrate the use of Sidekicks! and its anticipated functionality across several public service settings, including hospitals, outpatient clinics, and school systems, thereby coordinating the intervention efforts of various professionals involved in the treatment of children with ASD. Finally, limitations of the app (and of technology more generally) and the need for future research will be discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Low rates of depressed mood and depression diagnoses in a clinic review of children and adolescents with autistic disorder.

OBJECTIVES: The purpose of this study was to investigate the prevalence of depression diagnoses and related clinical data in an outpatient sample of youth with autistic disorder. METHODS: Records of 123 psychiatrically referred children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of autistic disorder were examined. Mood disorder diagnoses and chief complaints along with family mood disorder history were the primary variables analyzed. RESULTS: Four subjects (3%) presented with depressed mood. Irritability complaints were frequent (n=78, 63%). Six subjects (5%) received a mood disorder diagnosis; all with mood disorder, not otherwise specified. No subjects received a depressive disorder diagnosis. Family history of mood disorders was common. CONCLUSIONS: Findings raise questions about the appropriate characterization and potential misdiagnoses of depression in youth with autistic disorder.

Age at first autism spectrum disorder diagnosis: the role of birth cohort, demographic factors, and clinical features.

OBJECTIVE: This study sought to identify factors that may be associated with delays in autism spectrum disorder (ASD) diagnosis, including birth cohort, sociodemographic characteristics, and clinical features. METHODS: Participants included 1716 children and adolescents with ASD enrolled in the Autism Speaks Autism Treatment Network (AS-ATN) between the years 2008 and 2011. Data were collected at enrollment using AS-ATN parent- and clinician-report forms and standardized measures of I.Q., ASD symptoms, adaptive function, and psychiatric symptoms. RESULTS: Age at first ASD diagnosis was positively correlated with current age, suggesting a birth cohort effect. Sociodemographic and clinical features were also associated with age at diagnosis, even after controlling for current age. Hierarchical linear regression results showed that older current age, lower socioeconomic status (SES), higher I.Q. score, and lower levels of autism symptoms were associated with later age at initial diagnosis. There was also a significant interaction between current age and I.Q., with higher functioning children being diagnosed at younger ages than in previous years. CONCLUSIONS: Early diagnosis of ASD is critically important for improving access to interventions; however, many children experience diagnostic delays. In this sample, children from the most recent birth cohorts were diagnosed earlier, suggesting that early signs of ASD are being increasingly recognized. However, socioeconomic barriers to diagnosis still seem to exist. Children with less severe ASD symptoms and with higher I.Q. are also diagnosed at later ages. Efforts are still needed to reduce diagnostic disparities for families of low SES and to improve early recognition of more subtle symptoms.

Initial validity of the Logical Rorschach in the assessment of trauma.

Wagner's (2001) Logical Rorschach (LR) was designed to be a simple but reliable and valid system for assessing psychological distress and cognitive slippage using the Rorschach Inkblot Method (Exner, 2003). In this investigation, we administered the Rorschach to 50 adults with and without trauma histories. Scoring of the test followed both the Comprehensive System (CS; Exner, 2003) and the LR guidelines. Results indicate that the Perceptual Thinking Index (Exner, 2000, 2003), the CS-derived Trauma Content Index (Armstrong & Loewenstein, 1990) and Aggressive Past (Gacono & Meloy, 1994), and the LR Perceptual Accuracy Score (Wagner, 2001) scores were able to differentiate the 2 groups. Despite largely equivocal findings, it appears that some aspects of the LR may have some validity in the assessment of trauma-related phenomena.

Exploring the validity of the comprehensive trail making test.

The present study is the first independent investigation of the Comprehensive Trail Making Test (CTMT; Reynolds, 2002) with both clinical and non-clinical samples. We examined convergent and divergent validity by exploring relationships between the CTMT and other measures. Discriminant validity was examined by comparing CTMT scores of non-clinical and clinical groups. Results indicate that the CTMT was largely unrelated to measures of processing speed and nonverbal reasoning, verbal processing, and psychiatric symptoms. The CTMT Composite score was able to differentiate between clinical and non-clinical groups with a large effect size. Overall, although further research is needed, results tentatively suggest that the CTMT may be a useful addition to a multifaceted neuropsychological test battery.