Charon's size and an upper limit on its atmosphere from a stellar occultation.

Pluto and its satellite, Charon (discovered in 1978; ref. 1), appear to form a double planet, rather than a hierarchical planet/satellite couple. Charon is about half Pluto's size and about one-eighth its mass. The precise radii of Pluto and Charon have remained uncertain, leading to large uncertainties on their densities. Although stellar occultations by Charon are in principle a powerful way of measuring its size, they are rare, as the satellite subtends less than 0.3 microradians (0.06 arcsec) on the sky. One occultation (in 1980) yielded a lower limit of 600 km for the satellite's radius, which was later refined to 601.5 km (ref. 4). Here we report observations from a multi-station stellar occultation by Charon, which we use to derive a radius, R(C) = 603.6 +/- 1.4 km (1sigma), and a density of rho = 1.71 +/- 0.08 g cm(-3). This occultation also provides upper limits of 110 and 15 (3sigma) nanobar for an atmosphere around Charon, assuming respectively a pure nitrogen or pure methane atmosphere.

Oxytocin and autistic disorder: alterations in peptide forms.

BACKGROUND: Oxytocin (OT) is synthesized as a prohormone that is sequentially processed to peptides. These peptides are the bioactive amidated form (OT) and the C-terminal extended peptides, OT-Gly, OT-Gly-Lys and OT-Gly-Lys-Arg, which are designated together as OT-X. As an extension of our previous study finding decreased plasma OT in autism, studies were conducted to determine whether there were changes in OT peptide forms in autistic children. METHODS: Twenty eight male subjects (97 +/- 20 months; range, 70-139 months), diagnosed with DSM-IV autistic disorder through observation and semi-structured interview, were compared with 31 age-matched nonpsychiatric control subjects (106 +/- 22 months; range, 74-140 months). Using OT antisera with different specificity for the peptide forms, we measured plasma OT and OT-X in each group. RESULTS: T tests showed that there was a decrease in plasma OT (t = 4.4, p <.0001), an increase in OT-X (t = 2.3, p <.03) and an increase in the ratio of OT-X/OT (t = 4.5, p <.0001) in the autistic sample, compared with control subjects. CONCLUSIONS: The results suggest that children with autistic disorder show alterations in the endocrine OT system. Deficits in OT peptide processing in children with autism may be important in the development of this syndrome.

Plasma oxytocin levels in autistic children.

BACKGROUND: Social impairments are central to the syndrome of autism. The neuropeptide oxytocin (OT) has been implicated in the regulation of social behavior in animals but has not yet been examined in autistic subjects. METHODS: To determine whether autistic children have abnormalities in OT, midday plasma samples from 29 autistic and 30 age-matched normal children, all prepubertal, were analyzed by radioimmunoassay for levels of OT. RESULTS: Despite individual variability and overlapping group distributions, the autistic group had significantly lower plasma OT levels than the normal group. OT increased with age in the normal but not the autistic children. Elevated OT was associated with higher scores on social and developmental measures for the normal children, but was associated with lower scores for the autistic children. These relationships were strongest in a subset of autistic children identified as aloof. CONCLUSIONS: Although making inferences to central OT functioning from peripheral measurement is difficult, the data suggest that OT abnormalities may exist in autism, and that more direct investigation of central nervous system OT function is warranted.

Ventricular enlargement in child psychiatric patients: a controlled study with planimetric measurements.

Data from adult schizophrenic patients suggest that patients with enlarged ventricles have a poorer premorbid history and may have an earlier onset of their illness than patients with ventricles of normal size. The authors examined a group of child psychiatric patients to discover whether these children at risk for major psychopathology had enlarged ventricles. Twenty psychiatric patients showed significantly enlarged ventricles compared with 19 control patients. There were no clear relationships between the children's psychiatric diagnosis and ventricular size.

Psychiatric disability associated with the fragile X chromosome.

Fragile X (or Martin-Bell) syndrome, a common, genetic, mental retardation disorder is increasingly being recognized as a major cause of cognitive disability and psychiatric illness in boys. Here, we present a study in which relatives in 4 generations of a large family with the fra(X) chromosome were given comprehensive psychiatric evaluations in order to further describe the psychopathology associated with this condition. Three of 4 males with the fra(X) chromosome were found to have autistic behavior. An adult fra(X) male had a chronic schizoaffective disorder and mental retardation. In female relatives, a relationship was found between the fra(X) carrier status and psychopathology including schizoaffective and major affective disorders.

Subgroups of children with autism by cluster analysis: a longitudinal examination.

OBJECTIVES: A hierarchical cluster analysis was conducted using a sample of 138 school-age children with autism. The objective was to examine (1) the characteristics of resulting subgroups, (2) the relationship of these subgroups to subgroups of the same children determined at preschool age, and (3) preschool variables that best predicted school-age functioning. METHOD: Ninety-five cases were analyzed. RESULTS: Findings support the presence of 2 subgroups marked by different levels of social, language, and nonverbal ability, with the higher group showing essentially normal cognitive and behavioral scores. The relationship of high- and low-functioning subgroup membership to levels of functioning at preschool age was highly significant. CONCLUSIONS: School-age functioning was strongly predicted by preschool cognitive functioning but was not strongly predicted by preschool social abnormality or severity of autistic symptoms. The differential outcome of the 2 groups shows that high IQ is necessary but not sufficient for optimal outcome in the presence of severe language impairment.

Autism and genetic disorders.

The syndrome of autism has been documented as occurring in association with a wide variety of genetic conditions. Autistic patients with a coexistent genetic condition, however, are not behaviorally or developmentally distinct from autistic patients for whom there is no known etiology or associated organic condition. This report reviews the literature linking autistic behavior with genetic conditions. Genetic, neurodevelopmental, and neuropathological findings in three genetic conditions which frequently give rise to autism are presented in detail. On the basis of this review, two hypotheses are supported: autism is a behaviorally defined phenotype which arises from diverse causes of central nervous system (CNS) damage, and the autistic phenotype represents only one point along a continuum of psychological dysfunction resulting from CNS damage. Current theories of genetic influences on brain development are reviewed, with emphasis on the relationships among qualitative, quantitative, and temporal abnormalities of CNS maturation and behavioral dysfunction. A hypothesis of abnormal brain development resulting from dysfunctional myelination is proposed as a potential etiologic factor in autism.

Determination of a reference range for whole blood serotonin in a pediatric population using high pressure liquid chromatography with electrochemical detection.

Whole blood serotonin (5HT) concentrations were measured in a group of children and adolescents to determine a reference range for this population. Blood was collected after at least a 6-hour fast, mixed with ascorbic acid and EDTA, and frozen at -70 degrees C until analysis. 5HT was determined by HPLC with electrochemical detection. Matrix-matched whole blood standards and controls were used to determine 5HT concentrations, and monitor performance of the assay. 5HT concentrations in boys ranged from 0.53 to 3.13 mumol/L (mean = 1.27, SD = 0.47) while the range for girls was 0.63 to 2.46 mumol/L (mean = 1.21, SD = 0.47). There was no significant difference in 5HT concentrations between boys and girls, nor was there any significant change in 5HT concentration with age. The nonparametric central 95 percent reference range for boys and girls was determined to be 0.64-2.45 mumol/L.

Autism: the point of view from fragile X studies.

The relationship between the fragile X syndrome (FXS) and autism is reviewed. Shortly after the FXS was first described, it was noted that certain behaviors commonly found in afflicted individuals resemble certain features of autism. Research concerning a possible relationship between these conditions is summarized. The outcome of this research indicates that FXS is not a common cause of autism, although the number of individuals with FXS who meet diagnostic criteria for autism is higher than can be accounted for by chance. The major focus of this paper highlights that FXS is a well-defined neurogenetic disease that includes a cognitive behavioral phenotype, and has both a known biological cause and an increasing well-delineated pathogenesis. Autism is a behaviorally defined syndrome whose syndromic boundaries and biological causes are not known. These profound differences complicate comparisons and causal discussions. However, the behavioral neurogenetic information available about FXS suggests certain pathways for future research directed at elucidating the syndrome of autism.

Social initiations by autistic children to adults and other children.

Social initiations made by autistic and verbal-matched retarded children were recorded in two naturalistic situations. Frequencies of initiation to adults did not differ between groups, but the retarded children initiated much more frequently to peers. Most interactions for both groups were positive, but the autistic children engaged in more ritualized, and the retarded children more playful, initiations. The autistic children monitored the social environment more when forced into proximity with peers, whereas the retarded children initiated more in the unstructured situation. Autistic initiation to peers was unrelated to severity of autism, but was related to cognitive skills, including vocabulary and comprehension of affect, whereas retarded children's initiations were unrelated to cognitive level. Results are discussed in terms of the differences between adults and children as social stimuli, prerequisite skills for initiation to peers, and the relationship between social cognition and social behavior. It is suggested that autistic and retarded children differ in the quantity of their initiations to peers, and the quality of their initiations to adults, and that initiations to peers may be a particularly useful index of social development in autistic children. Results confirm the need of autistic children for highly structured social environments, and suggest an important role for the remediation of specific cognitive skills such as comprehension of others' affects.

Diagnosis and classification in autism.

This study compared four systems for the diagnosis of autism (DSM-III, DSM-III-R, DSM-IV, and ICD-10) with two empirically derived taxa of autism, and with three social subgroups of autism (Aloof, Passive, and Active-but-Odd) in 194 preschool children with salient social impairment. There were significant behavior and IQ differences between autistic and other-PDD groups for all four diagnostic systems, and a significant association was found (a) for Taxon B, diagnoses of autism, and the Aloof subgroup, and (b) for Taxon A, other-PDD, and the Active-but-Odd subgroup. Findings offer support for two major overlapping continua within idiopathic Pervasive Developmental Disorder.

Effects of fenfluramine on social behavior in autistic children.

Deficit in social interaction is a primary component of infantile autism. However, in the majority of drug studies, social interaction has not been measured consistently over time. Therefore, we examined, in a crossover design, the effect of fenfluramine on the social interactions of seven autistic children. Social interaction was measured one to three times per week, while the children were in open placebo, placebo, or drug phases of the study. The results demonstrated that the effect of fenfluramine on social interaction was inconsistent across children, with two children possibly demonstrating a tolerance to the behavioral effects of the drug. The results are discussed with respect to genetic and pharmacologic factors.

A case report of naltrexone treatment of self-injury and social withdrawal in autism.

The endogenous opiate release theory of self-injurious behavior (SIB) was investigated through double-blind placebo-controlled administration of naltrexone hydrochloride (Trexan) to a 14-year-old autistic and mentally retarded male for treatment of severe SIB. Results yielded a marked decrease in SIB during two phases of active drug treatment, though SIB did not revert to originally observed placebo levels during a second placebo phase. An increase in social relatedness also was observed during phases of active drug treatment. Opiate theories of self-injury and the possible interrelationship of self-injury with pituitary-adrenal arousal and with social relatedness are discussed.

Predictors and correlates of adaptive functioning in children with developmental disorders.

Autism is a developmental disorder marked by impairments in socialization, communication, and perseverative behavior and is associated with cognitive impairment and deficits in adaptive functioning. Research has consistently demonstrated that children with autism have deficits in adaptive functioning more severe than their cognitive deficits. This study investigates the correlates and predictors of adaptive functioning as measured by the Vineland Adaptive Behavior Scales in high- and low-functioning children with autism and their age and nonverbal IQ matched controls. Thirty-five 9-year-old children with high-functioning autism (HAD) were compared with 31 age-matched children with developmental language disorder (DLD), and 40 9-year-old children with low-functioning autism (LAD) were compared with 17 age-matched children with low IQ on adaptive functioning, IQ, autistic symptomology, and tests of language and verbal memory. Results indicate that both groups with autism were significantly impaired compared to their matched controls on Socialization and Daily Living, but not Communication and that these impairments were more pronounced in the HAD group than in the LAD group. Adaptive behavior was strongly correlated with autistic symptomology only in the HAD group. Regression analyses indicated that IQ was strongly predictive of adaptive behavior in both low-functioning groups, but tests of language and verbal memory predicted adaptive behavior in the higher functioning groups. Results suggest that IQ may act as a limiting factor for lower functioning children but higher functioning children are impaired by specific deficits, including autistic symptomology and impaired language and verbal memory.

Effects of naloxone and naltrexone on self-injury: a double-blind, placebo-controlled analysis.

The effects of naloxone hydrochloride (Narcan) and naltrexone hydrochloride (Trexan) on the pervasive self-injury of a 12-year-old autistic and mentally retarded girl were examined. Using separate multiple schedule (A1/B/B') and withdrawal (A-B-A1B-A1) single-subject experimental designs, we investigated the effects of both opiate antagonists in serial fashion under double-blind, placebo-controlled conditions. Results of the two studies showed that self-injury increased during the naloxone trial, whereas a decrease to near zero rates of self-injury was observed following treatment with naltrexone. The differential effect produced by the two drugs was discussed in terms of drug half-life and the operant conditioning theory of extinction. Follow-up data showing near zero rates of self-injury for 22 months following the conclusion of active treatment with naltrexone indicated that the intervention produced a durable result.

The Woodhaven short-term model reconsidered: a study of developmental growth and criteria for discharge.

This article concerns the issues surrounding discharge of mentally retarded clients from a short-term, intensive residential service setting. The Temple University Woodhaven Center is designed as a two-year setting for about 270 clients. They require intensive assistance in acquiring behaviors necessary for independent functioning and in learning appropriate social behavior, so that they can adapt to and thrive in a less restrictive, more integrated setting. Woodhaven, however, serves clients at all levels of retardation. The question arises: How is it decided who is to be discharged and when? Upon entry to Woodhaven, a contract is written with the family and client, specifying what behavioral changes are expected as preconditions for discharge. In this approach, a client should be discharged upon attainment of contract goals. A second approach uses adaptive behavior skills as a criterion of progress, and attempts to determine the level of skills displayed by other, similar clients who are already living in the community. This second, criterion-referenced approach is important not only for discharge decisions from one facility, but for broad service system planning as well. The results of the present study supported the notion of a two-year intensive residential program.

Social relatedness and autism: current research, issues, directions.

Social relatedness has recently become a primary focus of investigators in the field of autism. This shift to regarding disturbances in social relatedness as one of the defining manifestations of the disorder marks the movement of research on autistic disorder back to its origins, when Kanner first noted the "social and affective" symptoms of autism as pathognomonic. Currently, social impairment in autism is viewed as more pervasively characteristic of the disorder than any other single symptom. Further, there has been a recent proliferation of research designed to document the nature of social deficit in autism, and whether it is primarily affective, communicative, or cognitive in nature, or involves some combination of these three variables. This review summarizes recent research focusing on social relatedness in autism and discusses the implications of these findings.

The assessment of mood and affect in developmentally disabled children and adolescents: the Emotional Disorders Rating Scale.

There is an unmet need for a reliable method of evaluating disorders of mood and affect in developmentally disabled children and adolescents. Such a measure is required for both accurate diagnosis and treatment monitoring in this population. An extensive review of existing assessment techniques confirms that: (a) current techniques for the evaluation of emotional disorders in cognitively normal individuals are inappropriate for most children with developmental disabilities; and (b) current instruments designed for the assessment of developmentally disabled children pay inadequate attention to affective symptoms. In this paper, the preliminary version of a new instrument, the "Emotional Disorders Rating Scale for Developmental Disabilities" (EDRS-DD), designed to evaluate mood and affect in children and adolescents with developmental disabilities, is presented. A pilot study indicates that interrater agreement is good.

Is there a need for observationally based assessment of affective symptomatology in child and adolescent psychiatry?

There is growing dissatisfaction with current methods for rating affective symptoms in child and adolescent psychiatry. The need for additional reliable methods of evaluating mood disorders is significant. This annotation reviews the relative limitations of self-report and interview assessment techniques as contrasted with observationally based rating scales which offer additional advantages for assessment.

Screening strategies to inhibit the spread of AIDS.

In this paper we explore the costs and benefits of screening programs for the human immunodeficiency virus (HIV). Because of the low prevalence rate of the virus among the general population, the cost per detected case of a program to screen the population at large is very high. We show how this cost changes with the prevalence rate, and how screening high risk groups reduces the cost per detected case. Screening has little point, however, unless there are follow-up activities to reduce the continued spread of the virus. To this end, we present a modeling framework for determination of optimal policy alternatives after screening.