Edward R. Ritvo

Twenty‐year outcome for individuals with autism and average or near‐average cognitive abilities

Previous studies found substantial variability in adult outcome for people with autism whose cognitive functioning was within the near‐average and average ranges. This study examined adult outcome for 41 such individuals (38 men and 3 women) originally identified through an epidemiological survey of autism in Utah. Mean age at the time of their previous cognitive assessment was 7.2 years (SD=4.1, range=3.1–25.9 years) and at follow‐up was 32.5 years (SD=5.7 years, range=22.3–46.4 years). Outcome measures included standardized assessments of diagnostic status, cognitive ability, and adaptive behavior. Additional information collected concerned demographic variables, indicators of independence, social relationships, medical and psychiatric conditions, and social service use. Outcomes for this sample were better than outcomes described in previous work on individuals with similar cognitive functioning. For example, half of the participants were rated as “Very Good” or “Good” on a global outcome measure. As in previous studies, there was considerable variability in measured cognitive ability over time. Over half of the sample had large gains or losses of cognitive ability of greater than 1 standard deviation. Cognitive gain was associated with better outcome, as was better adaptive functioning. While all participants had baseline IQs in the nonimpaired range, there was limited evidence to support the use of other early childhood variables to predict adult outcome.

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.

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.

Decreased postrotatory nystagmus in early infantile autism

IN 1943 Kanner’ described the syndrome of early infantile autism and defined four features he considered pathognomonic of the disease: [l] inability to relate to people, [2] failure to use language for communication, [3] apparent desire to be alone and to preserve sameness in the environment, and [4] preoccupation with certain objects. During the ensuing twenty-five years other investigators have described similar children, using different theoretical perspectives and with differing notions of etiology. Thus, children with many symptoms in common are diagnosed today as having schizophrenic reaction of childhood,2 atypical ego development,s symbiotic psychosis,4 or “unusual sensitivities.”s We have recently reviewed637 our clinical experience with more than 150 such children, as well as the relevant psychiatric, neurologic, and neurophysiologic literature. From this perspective, it appears that most of the children referred to by the above diagnostic labels are suffering from a unitary disease process. Their symptoms can be grouped into five subclusters involving disturbances of [ 11 perception, [2] motility, [ 31 developmental rate, [4] relating, and [ 5 ] language. We have suggested that the disturbances of perception, motility, and developmental rate are primarily expressive of organic dysfunction and underlie the disturbances of relating and language. For example, such children fail to respond completely to sounds which at other times evoke screaming and panic-like reactions. At an early age, they may be referred for audiologic evaluation because of questioned deafness,8 yet careful examination will reveal that they respond to such sounds as a distant door slamming. A child who is reported to avoid eye contact, look through people, and ignore objects placed in front of him will spend hours staring at tops, record players, or cracks in a wall. These children are usually panicked by riding in elevators and being tossed in the air; yet they will spin themselves uninterruptedly for hours. These apparently paradoxical responses give the clinical impression that normal homeostatic regulation of perception cannot be maintained within the central nervous system of such children and that they experience perceptual inconstancy.6 Based on these clinical observations, experiments have been designed which indicate vestibular dysfunction during certain stages of sleep. It was found that the vestibularly mediated phasic inhibition of auditory-evoked responses seen in normal children during the eye movement bursts of rapid eye movement (REM) sleep was not present in a group of young autistic children.* Instead there was a relative enhancement of the amplitude of the late component of the auditory-evoked response during the eye movement bursts. Furthermore, there was a decreased duration of individual eye movement bursts during REM sleep in the youngest autistic children.10 As the eye movement bursts of REM sleep were mediated by the vestibular nuclei,’lJ‘ these

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 auditory evoked response in normal and autistic children during sleep

Abstract 1. 1. The auditory averaged evoked response (AER) was measured at the vertex in age-matched groups of normal and autistic children during Stage 2 and REM sleep and during the ocular quiescent and eye movement burst phases of REM sleep. Amplitudes and latencies of wave N2 of the auditory AER were compared during these different sleep stages. 2. 2. In a group of sixteen autistic children under 5 years 1 month old, the relative amplitude of wave N2 during REM sleep (relative to Stage 2 sleep) was significantly greater than in a group of sixteen normal children. 3. 3. In a group of seventeen autistic children under 61 months old, the relative amplitude of wave N2 during the eye movement bursts (relative to ocular quiescence) was greater than that measured in a group of eighteen normal children. 4. 4. In a group of ten normal children under 61 months old, there was no appreciable difference between amplitudes of wave N2 obtained during the ocular quiescent phase of REM sleep and Stage 2 sleep. In contrast, amplitudes of wave N2 obtained during the eye movement burst phase of REM sleep were significantly smaller than during Stage 2. 5. 5. A group of eleven autistic children showed significantly larger relative amplitudes of wave N2 during both the ocular quiescent and the eye movement burst phases of REM sleep (relative to Stage 2 sleep) than did the group of ten normal children. The relative reduction of response amplitude during the eye movement bursts in normals was markedly overridden in these autistic subjects. 6. 6. The finding that relative reduction of response amplitude during REM sleep in normals is confined to the eye movement burst phase was related to the concept of phasic inhibition distinct from tonic inhibition during REM sleep. The phasic inhibition has been shown to be mediated by vestibular nuclei. The overriding of phasic inhibition in the autistic children was related to clinical observations suggesting vestibular dysfunction and faulty registration of the significance of sensory input.

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.

Rapid eye movement (REM) activity in normal and autistic children during REM sleep.

Thirty normal children (aged 3–68 months) and 16 autistic children (aged 36–62 months) were recorded during nonmedicated sleep and data pertaining to rapid eye movements (REM) were measured during the first three REM periods of the night. When time of night from which data were gathered was held constant, normal children showed a significant relationship between age and the organization of eye movements into discrete bursts. When autistic children were compared to age-matched normal controls, they showed an immaturity in this phenomena, their results being similar to those found in children less than 18 months of age. Such an immaturity could result from dysfunction at a number of diverse levels and sites in the central nervous system.

Effects of L-dopa in autism

A study was designed to determine if blood serotonin concentrations could be lowered in autistic children by the administration of L-dopa and, if so, to observe possible clinical or physiological changes. Following a 17-day placebo period, four hospitalized autistic boys (3, 4, 9, and 13 years of age) received L-dopa for 6 months. Results indicated a significant decrease of blood serotonin concentrations in the three youngest patients, a significant increase in platelet counts in the youngest patient, and a similar trend in others. Urinary excretion of 5HIAA decreased significantly in the 4-year-old patient and a similar trend was noted in others. No changes were observed in the clinical course of the disorder, the amount of motility disturbances (hand-flapping), percent of REM sleep time, or in measures of endocrine function (FSH and LH). Possible mechanisms by which L-dopa lowered blood serotonin concentrations, increased platelet counts, and yet failed to produce other changes are discussed.