Sally Ozonoff

Practice parameter: Screening and diagnosis of autism Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society

Article abstract Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.

Teaching Theory of Mind: A New Approach to Social Skills Training for Individuals with Autism.

This study examined the effectiveness of a social skills training program for normal-IQ adolescents with autism. Five boys participated in the 4 1/2-month treatment condition; four boys matched on age, IQ, and severity of autism constituted the no-treatment control group. In addition to teaching specific interactional and conversational skills, the training program provided expliciand systematic instruction in the underlying social-cognitive principles necessary to infer the mental states of others (i.e., theory of mind). Pre- and post-intervention assessment demonstrated meaningful change in the treatment groups performance on several false belief tasks, but no improvement in the control sample. No changes, however, were demonstrated on general parent and teacher ratings of social competence for either group.

Effectiveness of a Home Program Intervention for Young Children with Autism.

This project evaluated the effectiveness of a TEACCH-based home program intervention for young children with autism. Parents were taught how to work with their preschool autistic child in the home setting, focusing on cognitive, academic, and prevocational skills essential to later school success. To evaluate the efficacy of the program, two matched groups of children were compared, a treatment group and a no-treatment control group, each consisting of 11 subjects. The treatment group was provided with approximately 4 months of home programming and was tested before and after the intervention with the Psychoeducational Profile-Revised (PEP-R). The control group did not receive the treatment but was tested at the same 4-month interval. The groups were matched on age, pretest PEP-R scores, severity of autism, and time to follow-up. Results demonstrated that children in the treatment group improved significantly more than those in the control group on the PEP-R subtests of imitation, fine motor, gross motor, and nonverbal conceptual skills, as well as in overall PEP-R scores. Progress in the treatment group was three to four times greater than that in the control group on all outcome tests. This suggests that the home program intervention was effective in enhancing development in young children with autism.

A longitudinal study of executive function and theory of mind development in autism

Both executive function and theory of mind impairment have been suggested as primary deficits of autism. One test of the primacy of a deficit is its persistence and stability throughout development. This longitudinal study examined development of executive function and theory of mind abilities over a 3-year time period, comparing nonretarded autistic adolescents with learning-disabled controls matched on age, IQ, gender, and socioeconomic status (SES). Results indicate that both executive function and theory of mind abilities are seriously deficient in autistic individuals, improve little with development, may never reach normal functioning levels, and appear to eventually hit a developmental ceiling. Developmental variables showed little relationship to overall task performance or improvement in either cognitive domain. The similar developmental trajectories of executive function and theory of mind performance found in this investigation suggest that these skills may be related and interdependent, rather than independent modules of cognitive function. Implications for the neurological basis of autism and intervention are also discussed.

DSM-IV-Defined Asperger Syndrome: Cognitive, Behavioral and Early History Differentiation from High-Functioning Autism.

This study compared 2 3 children with high-functioning autism with 12 children with Asperger syndrome, both defined according to strict DSM-IV diagnostic criteria. The groups were well matched on chronological age, gender and intellectual ability. Three possible sources of difference between Asperger syndrome and highfunctioning autism were examined: cognitive function, current symptomatology and early history. We found few group differences in current presentation and cognitive function, but many early history differences. The Asperger syndrome group generally demonstrated less severe early symptoms, a milder developmental course and better out-come than the high-functioning autism group. Many of the group dif-ferences appeared secondary to the initial group definition process, however. Overall, the results suggest that Asperger syndrome and high-functioning autism involve the same fundamental symptomatology, differing only in degree or severity.

Further Evidence of Intact Working Memory in Autism

Earlier investigations have found mixed evidence of working memory impairment in autism. The present study examined working memory in a high-functioning autistic sample, relative to both a clinical control group diagnosed with Tourette Syndrome and a typically developing control group. No group differences were found across three tasks and five dependent measures of working memory. Performance was significantly correlated with both age and IQ. It is concluded that working memory is not one of the executive functions that is seriously impaired in autism. We also suggest that the format of administration of working memory tasks may be important in determining whether or not performance falls in the impaired range.

Inhibitory function in nonretarded children with autism

This study examined inhibitory function in nonretarded children with autism (n = 13) and normally developing controls (n = 13) matched on age and IQ. Tasks measuring motor and cognitive components of inhibition were administered to both groups. On the Stop-Signal paradigm, children with autism were able to inhibit motor responses to neutral and prepotent stimuli as well as control subjects. On the Negative Priming task, the groups were equally capable of inhibiting processing of irrelevant distractor stimuli in a visual display. Results suggest that at least two components of inhibition are spared in individuals with autism, standing in contrast to flexibility and other executive deficits that have been found in previous studies. These findings may help distinguish children with autism from those with other neurodevelopmental conditions that involve executive dysfunction.

An Exploration of Right-Hemisphere Contributions to the Pragmatic Impairments of Autism

This study examined the potential contribution of the right hemisphere to the communicative impairments of autism. Pragmatic language measures sensitive to right-hemisphere damage were administered to nonretarded adults with autism and to controls matched on age and intellectual ability. The experimental battery included measures of humor, inference, and indirect request comprehension. Autistic subjects performed significantly less well than controls on all measures, replicating results of an earlier investigation by Rumsey and Hanahan (Journal of Clinical and Experimental Neuropsychology, 12, 81, 1990). The performance of the autistic group on the three tasks was also similar to that of right-hemisphere stroke patients reported previously (Molloy, Brownell, & Gardner, in Y. Joanette and H. M. Brownell (Eds.), Discourse ability and brain damage: Theoretical and empirical perspectives, New York: Springer-Verlag, 1990,pp. 113-130). Generalizability of these results and implications for the neuropathology of autism are discussed.

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder

OBJECTIVE To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Executive Functions in Autism

Although autism has been relatively well described at the symptom level (American Psychiatric Association, 1987; Rapin, 1991; Rutter, 1978a; Rutter & Schopler, 1987), the nature of the underlying processes responsible for the behavioral manifestations of the disorder is not yet clear. As Rutter (1988) emphasized, a thorough understanding of any developmental psychopathology requires a shift from descriptive accounts and statistical approaches to a focus on causal processes and underlying psychobiologic mechanisms. Unfortunately, in the field of autism, there remains a large gap between our ability to recognize and diagnose the disorder and our understanding of the impairments underlying it. Identification of so-called “primary deficits” is critical for the eventual understanding of the neural substrate of the disorder. It will also likely have implications for early diagnosis, treatment, and educational remediation (Frith, 1988).