B. J. Freeman

Preliminary Observations on the Effect of Fenfluramine on Blood Serotonin and Symptoms in Three Autistic Boys

THE syndrome of autism is a pervasive developmental disorder. It is diagnosed by the presence before 30 months of age of disturbances in the rate of development and coordination of physical, social...

A scale for rating symptoms of patients with the syndrome of autism in real life settings.

A scale was developed to assess effects of treatment on 47 pathognomic behaviors in patients with the syndrome of autism. It is applicable in natural settings by nonprofessional raters who can be rapidly trained to achieve significant interobserver agreement, is rapidly scored by hand, and can be repeated frequently without affecting interobserver agreement. The scale has been used successfully in over a dozen medical centers throughout the country and in several schools.

Vineland Adaptive Behavior Scale Scores as a Function of Age and Initial IQ in 210 Autistic Children

Human growth modeling statistics were utilized to examine how Vineland Adaptive Behavior Scale (VABS) scores changed in individuals with autistic disorder as a function of both age and initial IQ. Results revealed that subjects improved with age in all domains. The rate of growth in Communication and Daily Living Skills was related to initial IQ while rate of growth in Social Skills was not. Results should provide hope for parents and further support for the importance of functional social-communication skills in the treatment of autism.

Assessment in Multisite Randomized Clinical Trials of Patients with Autistic Disorder: The Autism RUPP Network

Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.

Effects of Fenfluramine on 14 Outpatients with the Syndrome of Autism

Fenfluramine was administered to 14 outpatients with the syndrome of autism in a double blind crossover study (ABA design) to determine its effects on blood serotonin concentrations, platelet counts, and symptomatic behaviors. Blood serotonin concentrations decreased an average of 51% after 1 month on medication and returned to baseline levels within 1 month after return to placebo. Platelet counts were unaffected. Serial observation scales, developmental profiles, intelligence scales, and parental interviews and diaries were obtained. They revealed that certain symptoms improved significantly while patients were on medication and worsened when placebo was reinstituted. Patients with both normal and elevated baseline serotonin had symptomatic improvements. No adverse reactions to medication nor clinically significant side effects were noted. Definitive conclusions regarding relationships among initial serotonin levels, clinical features, and symptom responses cannot yet be drawn since data are available on only 14 patients. The encouraging findings in these 14 patients are being studied further at 18 medical centers throughout the United States on approximately 150 patients.

Gene mapping studies with the syndrome of autism

The UCLA Registry for Genetic Studies of Autism had collected data on 308 families by February 1, 1983. A subsample of 46 families withat least two affected children was analyzed for evidence of a Mendelian mode of inheritance. The data were consistent with an autosomal recessive mode of inheritance (Ritvo, E. R., Spence, M. A., Freeman, B. J. Mason-Brothers, A., Mo. A., and Marazita, M. L., 1985, American Journal of Psychiatry, in press). Thirty-four of these families were subjected to gene linkage analyses with 30 standard phenotypic gene markers. There is no evidence of linkage between the purported autism locus and HLA, either from analysis of HLA haplotype sharing or fromlod scores. In addition, close linkage with autism, i.e., ≤5% recombination, could be excluded for 19 of the other autosomal genetic markers. The largest positivelod score, 1.04, was with haptoglobin (HP), at recombination frequencies of 10% in males and 50% in females. Normal C-and Q-banded chromosome polymorphisms were evaluated for association with autism and as additional linkage markers.

The stability of cognitive and behavioral parameters in autism: a twelve-year prospective study.

Sixty-two autistic patients enrolled in a prospective study an average of 12 years ago. Current retesting results are now available on 53 of the original 62 patients (85.5%). Results indicate that 36 (67.9%) achieved scores within their original IQ group. Twelve (22.6%) moved up IQ groups and five (9.4%) moved down. Of particular clinical importance is the observation that Vineland Adaptive Behavior Scores were consistently lower than cognitive scores, and maladaptive behaviors occurred with equal frequency in the high, medium, and low IQ groups. The implications of this new data for understanding the natural history of autism, educational and vocational planning, and future research are discussed.

Guidelines for evaluating intervention programs for children with autism.

It is now well recognized that early diagnosis and intervention improves the prognosis for children with autism. It is crucial that professionals be aware and sensitive to the needs of autistic persons and their families. We must never lose sight of the long-term goal of treatment and must not become so infatuated with any one treatment that we fail to provide the education parents need. It is incumbent upon us, as professionals, to educate parents and help them evaluate the myriad of information with which they are bombarded. In this article a framework for thinking about autism and principles of evaluation are reviewed. Components of appropriate early intervention programs are then described and guidelines for evaluating alternative treatments are provided.

The stability of cognitive and linguistic parameters in autism: a five-year prospective study.

Sixty-two patients with the syndrome of autism were selected for 5-year prospective annual administrations of cognitive and linguistic scales. Results revealed that (1) the majority of subjects (77%) initially scored in the retarded ranges on cognitive tests, (2) cognitive test scores remained stable at yearly intervals for 5 years (only 8 of 62 subjects (12.9%) changed IQ groups), (3) initial scores were predictive of future educational placement (only 7 of 62 subjects (11.3%) changed classrooms after initial placement), and (4) language scores paralleled in stability and predictability cognitive scores. Implications for educational goals for autistics are discussed.

Comparison between diagnostic instruments for identifying high-functioning children with autism

Two instruments for identifying autism in children and adolescents with intellectual abilities in the normal range were compared. Diagnostic tools consisted of the Autism Behavior Checklist (ABC) and the Autism Diagnostic Interview (ADI). The sample was composed of 18 children who were all diagnosed as having either infantile autism or infantile autism, residual state based on DSM-III criteria by a clinical team using observations, parental interviews, and interactions with the children. Only 4 of the children met diagnostic cutoffs for autism on the current ABC but all met criteria for diagnosis on the ABC using parental recall of the childs behavior at 3–5 years of age. The ADI had somewhat greater specificity in that 3 children did not meet criteria for diagnosis although 2 of these children also received ABC scores based on parental recollection that were in the borderline range.