Challenges in assessing change in autistic adults: scale limitations and discrepancies in reporting in clinical trials.

Autism Spectrum Disorder (ASD) is a developmental disorder marked by deficits in social communication and social interaction, together with restricted and/or repetitive patterns of behaviours, activities or interests. As more adults are being diagnosed with ASD, and more diagnosed children are aging into adulthood, the need for effective treatments and support services for autistic adults is quickly growing. As such, clinical research targeting autistic adults has emerged in recent years. Currently, caregiver ratings are commonly used as outcome measures in child treatment studies, but these scales present challenges when utilised to assess the autistic adult population. In this commentary, we seek to unveil the difficulties and obstacles in assessing change in clinical treatment trials for autistic adults. Specifically, this article uses case examples to explore the limitations of rating scales. Steps for improving the accuracy of ratings, and for developing novel self-rating scales for autistic adults are discussed. It is hoped that in exploring these difficulties in more depth, clinical research with adult ASD populations will continue to improve and that reliable, valid and sensitive outcome measures will be developed to ensure the highest quality treatments emerge.

Intranasal oxytocin versus placebo for hyperphagia and repetitive behaviors in children with Prader-Willi Syndrome: A randomized controlled pilot trial.

OBJECTIVE: The effects of intranasal oxytocin and placebo on hyperphagia and repetitive behaviors were compared in children and adolescents with Prader Willi Syndrome (PWS). METHODS: Children and adolescents with PWS were enrolled in an 8-week double-blind placebo-controlled intranasal oxytocin randomized trial. Twenty-three (23) subjects were assigned to oxytocin (N = 11) or placebo (N = 12). Hyperphagia was measured with the Hyperphagia Questionnaire (HQ), and repetitive behavior was measured with Repetitive Behavior Scale- Revised (RBS-R). RESULTS: There were modest significant treatment by-time interactions indicating reduction in hyperphagia and repetitive behaviors across time for placebo but no reduction for oxytocin. Total HQ score showed a greater average reduction of 1.81 points/week for the placebo group vs. oxytocin, with maximum reduction at week 4. There were also greater reductions on HQ-Drive and HQ-Behavior subscales on placebo vs. oxytocin. RBS-R subscales followed similar patterns to the HQ, with a significantly greater reduction in sameness subscale behaviors (average 0.825 points/week) in the placebo group compared to the oxytocin group. Oxytocin was well tolerated, and the only adverse event that was both more common and possibly related to oxytocin vs. placebo was nocturia (n = 1 vs 0). CONCLUSION: Placebo was associated with modest improvement in hyperphagia and repetitive behaviors in childhood PWS whereas intranasal oxytocin was not associated with improvement in these domains. More work is needed to understand the meaning and mechanism of these findings on hyperphagia and repetitive behaviors in PWS.

Oxytocin and Prader-Willi Syndrome.

In the chapter, we explore the relationship between the peptide hormone, oxytocin (OT), and behavioral and metabolic disturbances observed in the genetic disorder Prader-Willi Syndrome (PWS). Phenotypic and genotypic characteristics of PWS are described, as are the potential implications of an abnormal OT system with respect to neural development including the possible effects of OT dysfunction on interactions with other regulatory mediators, including neurotransmitters, neuromodulators, and hormones. The major behavioral characteristics are explored in the context of OT dysfunction, including hyperphagia, impulsivity, anxiety and emotion dysregulation, sensory processing and interoception, repetitive and restrictive behaviors, and dysfunctional social cognition. Behavioral overlaps with autistic spectrum disorders are discussed. The implications of OT dysfunction on the mechanisms of reward and satiety and their possible role in informing behavioral characteristics are also discussed. Treatment implications and future directions for investigation are considered.

The Study to Explore Early Development (SEED): a multisite epidemiologic study of autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) network.

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes.

A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders.

OBJECTIVE: The effects of fluoxetine and placebo on repetitive behaviors and global severity were compared in adults with autism spectrum disorders (ASDs). METHOD: Adults with ASDs were enrolled in a 12-week double-blind placebo-controlled fluoxetine trial. Thirty-seven were randomly assigned to fluoxetine (N=22) or placebo (N=15). Dosage followed a fixed schedule, starting at 10 mg/day and increasing as tolerated up to 80 mg/day. Repetitive behaviors were measured with the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale; the Clinical Global Impression (CGI) improvement scale was used to rate improvement in obsessive-compulsive symptoms and overall severity. RESULTS: There was a significant treatment-by-time interaction indicating a significantly greater reduction in repetitive behaviors across time for fluoxetine than for placebo. With overall response defined as a CGI global improvement score of 2 or less, there were significantly more responders at week 12 in the fluoxetine group than in the placebo group. The risk ratio was 1.5 for CGI global improvement (responders: fluoxetine, 35%; placebo, 0%) and 1.8 for CGI-rated improvement in obsessive-compulsive symptoms (responders: fluoxetine, 50%; placebo, 8%). Only mild and moderate side effects were observed. CONCLUSIONS: Fluoxetine treatment, compared to placebo, resulted in significantly greater improvement in repetitive behaviors, according to both the Yale-Brown compulsion subscale and CGI rating of obsessive-compulsive symptoms, as well as on the CGI overall improvement rating. Fluoxetine appeared to be well tolerated. These findings stand in contrast to findings in a trial of citalopram for childhood autism.