Ann T. Phillips

Oxytocin increases retention of social cognition in autism.

BACKGROUND Oxytocin dysfunction might contribute to the development of social deficits in autism, a core symptom domain and potential target for intervention. This study explored the effect of intravenous oxytocin administration on the retention of social information in autism. METHODS Oxytocin and placebo challenges were administered to 15 adult subjects diagnosed with autism or Aspergers disorder, and comprehension of affective speech (happy, indifferent, angry, and sad) in neutral content sentences was tested. RESULTS All subjects showed improvements in affective speech comprehension from pre- to post-infusion; however, whereas those who received placebo first tended to revert to baseline after a delay, those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task. CONCLUSIONS These results are consistent with studies linking oxytocin to social recognition in rodents as well as studies linking oxytocin to prosocial behavior in humans and suggest that oxytocin might facilitate social information processing in those with autism. These findings also provide preliminary support for the use of oxytocin in the treatment of autism.

A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism

Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.9±4.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

Infants' Ability To Connect Gaze and Emotional Expression to Intentional Action.

Four studies investigated whether and when infants connect information about an actors affect and perception to their action. Arguably, this may be a crucial way in which infants come to recognize the intentional behaviors of others. In Study 1 an actor grasped one of two objects in a situation where cues from the actors gaze and expression could serve to determine which object would be grasped, specifically the actor first looked at and emoted positively about one object but not the other. Twelve-month-olds, but not 8-month-olds, recognized that the actor was likely to grasp the object which she had visually regarded with positive affect. Studies 2, 3, and 4 replicated the main finding from Study 1 with 12- and 14-month-olds and included several contrasting conditions and controls. These studies provide evidence that the ability to use information about an adults direction of gaze and emotional expression to predict action is both present, and developing at the end of the first year of life.

Targeted treatments for symptom domains in child and adolescent autism

CONTEXT The number of people with autism spectrum disorders has dramatically increased over the past decade, and problem behaviours in autism are an increasing challenge to families, schools, physicians, and other health-care professionals. Pharmacological treatments can effectively target problem behaviours associated with autism. STARTING POINT Recently, L Namerow and colleagues (J Dev Behav Pediatr 2003; 24: 104-08) presented preliminary data in children and adolescents with autism treated with citalopram, which suggested that selective serotonin-reuptake inhibitors are useful in the reduction of symptom domains such as repetitive behaviours and mood disorders. J McCracken and colleagues (N Engl J Med 2000; 347: 314-21) showed that the atypical antipsychotic risperidone reduced serious behavioural problems, such as tantrums, aggression, or self-injury in children with autism and in children with below-average intelligence quotients. These and other studies show how developments in study design, selection of patients, and outcome measures have allowed treatment trials in autism to progress beyond anecdotal reports and case observations, and show reduction in the severity of specific symptom domains within these disorders. WHERE NEXT? In therapeutic intervention the risk of treatment toxicity must be balanced against the benefits of improved symptom severity. The newer methods enable informed decisions about which patients will benefit from which treatments. Other symptom domains within autism and effects on development need to be evaluated in adequately designed clinical trials. Future strategies include extending treatment to children as young as the preschool years.

Impact of Recent Findings on Study Design of Future Autism Clinical Trials

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.

Children's reasoning about physics within and across ontological kinds

Reasoning about seven physics principles within and across ontological kinds was examined among 188 5- and 7-year-olds and 59 adults. Individuals in all age groups tended to appropriately generalize what they learned across ontological kinds. However, children also showed sensitivity to ontological kind in their projections: when learning principles with reference to people they were more likely to assume that the principles apply to another person than to an inanimate object, and when learning with reference to an inanimate object they were more likely to assume that the principles apply to another inanimate object than to a person. Five-year-olds, but not 7-year-olds, projected concepts learned about people to a greater extent than principles learned about inanimate objects, closely paralleling the findings of Carey for the biological domain (Carey, S. (1985). Conceptual change in childhood. Cambridge, MA: MIT Press). Results from a separate sample of 22 5-year-olds suggest that the primary findings cannot be explained by response perseveration. The present findings indicate that children understand physics principles that apply to both animate and inanimate objects, but distinguish between these ontological kinds.

Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders

Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains: repetitive behaviours, social deficits, and language abnormalities. There is evidence that abnormalities exist in the serotonin (5-HT) system in autism spectrum patients. Furthermore, 5-HT is known to play a role in repetitive and social behaviours. This study examined the effect of m-chlorophenylpiperazine (m-CPP) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind, m-CPP and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviours: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo. Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls, with neither group responding to placebo. This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders, as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system.