Variation in early developmental course in autism and its relation with behavioral outcome at 3-4 years of age.

The aims of the present study were to describe variations in the early course of development in autism by utilizing an in-depth parent interview that incorporated techniques to improve accuracy of parent recall, and to examine the relation between variations in early developmental course in autism and behavioral outcome at 3-4 years of age. The Early Development Interview, which consisted of questions about child's behavior in several domains from birth through 2 years of age, was created and administered to parents of 72 3-4-year-old children with autism spectrum disorder and 34 3-4-year-old children with developmental delay, who were matched on mental and chronological age, and 39 1-4-year-old typically developing children, who were matched to the clinical groups on mental age. At 3-4 years of age, children were administered standardized measures (some clinician administered and some parent report); these included verbal and nonverbal IQ, autism symptom severity, and adaptive and aberrant behavior. Based on the Early Development Interview, children with autism spectrum disorder (ASD) were reported to have elevated symptoms in the social and regulatory domains by 3-6 months. By 12-15 months, parents of children with ASD reported significantly higher levels of social symptoms than parents of children with developmental delay. At 3-4 years of age, children with autism with early vs. late onset of symptoms, and with vs. without a history of loss of skills (regression) were not found to differ on standardized tests of verbal and nonverbal IQ and observational measures of autism symptom severity.

A randomized, double-blind, placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism.

OBJECTIVE: To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms. METHOD: Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated (ages between 3 and 12 years, mean IQ = 55). Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups: biologic secretin (2 CU/kg), synthetic secretin (0.4 microg/kg), and placebo. Measures collected 1 week before and 4 weeks after infusion included autism symptoms, language skills, and problem behaviors, gathered from parents, teachers, and investigators, who were all blind to treatment. Two-factor, repeated-measures analyses of variance (3 treatment levels by 2 repeated measures, pre- and postinfusion) were used to examine efficacy. RESULTS: Direct observation measures did not show change over time related to secretin. Parent reports showed an overall reduction of symptom severity for all treatment groups, including the placebo group. One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups. CONCLUSIONS: No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately.

Early social attention impairments in autism: social orienting, joint attention, and attention to distress.

This study investigated social attention impairments in autism (social orienting, joint attention, and attention to another's distress) and their relations to language ability. Three- to four-year-old children with autism spectrum disorder (ASD; n = 72), 3- to 4-year-old developmentally delayed children (n = 34), and 12- to 46-month-old typically developing children (n = 39), matched on mental age, were compared on measures of social orienting, joint attention, and attention to another's distress. Children with autism performed significantly worse than the comparison groups in all of these domains. Combined impairments in joint attention and social orienting were found to best distinguish young children with ASD from those without ASD. Structural equation modeling indicated that joint attention was the best predictor of concurrent language ability. Social orienting and attention to distress were indirectly related to language through their relations with joint attention. These results help to clarify the nature of social attention impairments in autism, offer clues to developmental mechanisms, and suggest targets for early intervention.

Case Study of the Development of an Infant with Autism from Birth to Two Years of Age.

This report describes a case study of the development of an infant with autism who was observed closely by professionals from birth and to whom a comprehensive psychological evaluation was administered at approximately 1 and 2 years of age. During the first 6 months of life, this infant displayed difficulties in oral motor coordination and muscle tone that fluctuated between hypotonia and hypertonia. He startled easily, had poor state regulation, and was hypersensitive to touch. Notably, however, during the first 6 months, this infant vocalized and responded socially to others by smiling and cooing. During the second half of the first year, he continued to demonstrate diffuse sensorimotor difficulties and diminished oral motor control. Hypersensitivity now extended to a wider range of stimuli. He had problems in sleep regulation. Motor stereotypies, including rocking, head banging, and toe walking, were observed. Difficulties in the domain of social interaction began to emerge during the second 6 months, including poor eye contact, failure to engage in imitative games, and lack of imitative vocal responses. By a little over 1 year of age, this infant met diagnostic criteria for autism based on the Autism Diagnostic Interview. There were several domains in which this toddler with autism did not show impairments. In the areas of immediate memory for actions, working memory, response inhibition, and speech perception, this 1-year old with autism displayed no evidence of significant impairment on the tests administered. This case study offers clues regarding the nature of autism at its earliest stages. Understanding early development in autism will be important for developing early screening and diagnostic tools.

Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation.

Previous work based on observations of home videotapes indicates that differences can be detected between infants with autism spectrum disorder and infants with typical development at 1 year of age. The present study addresses the question of whether autism can be distinguished from mental retardation by 1 year of age. Home videotapes of first birthday parties from 20 infants later diagnosed with autism spectrum disorder, 14 infants later diagnosed with mental retardation (without autism), and 20 typically developing infants were coded by blind raters with respect to the frequencies of specific social and communicative behaviors and repetitive motor actions. Results indicated that 1-year-olds with autism spectrum disorder can be distinguished from 1-year-olds with typical development and those with mental retardation. The infants with autism spectrum disorder looked at others and oriented to their names less frequently than infants with mental retardation. The infants with autism spectrum disorder and those with mental retardation used gestures and looked to objects held by others less frequently and engaged in repetitive motor actions more frequently than typically developing infants. These results indicate that autism can be distinguished from mental retardation and typical development by 1 year of age.

Neurocognitive function and joint attention ability in young children with autism spectrum disorder versus developmental delay.

Studies have shown that young children with autism are not impaired on prefrontal tasks relative to what would be expected for their mental age, raising questions about the executive dysfunction hypothesis of autism. These studies did not include ventromedial prefrontal tasks, however. The present study examined whether young children with autism spectrum disorder (ASD) are impaired on ventromedial prefrontal tasks, and whether performance on such tasks is correlated with a core autism symptom, joint attention ability. Seventy-two 3- to 4-year-old children with ASD, 34 3- to 4-year-old developmentally delayed children, and 39 12- to 46-month-old typically developing children, matched on mental age, were administered ventromedial and dorsolateral prefrontal tasks and joint attention tasks. Children with ASD performed similarly to comparison groups on all executive function tasks, indicating that at this early age, there is no autism-specific pattern of executive dysfunction. Ventromedial, but not dorsolateral, prefrontal task performance was strongly correlated with joint attention ability, however. The ventromedial prefrontal cortex is hypothesized to play a role in the development of joint attention and possibly some aspects of the autistic syndrome.

Presence of large deletions in kindreds with autism.

Autism is caused, in part, by inheritance of multiple interacting susceptibility alleles. To identify these inherited factors, linkage analysis of multiplex families is being performed on a sample of 105 families with two or more affected sibs. Segregation patterns of short tandem repeat polymorphic markers from four chromosomes revealed null alleles at four marker sites in 12 families that were the result of deletions ranging in size from 5 to >260 kb. In one family, a deletion at marker D7S630 was complex, with two segments deleted (37 kb and 18 kb) and two retained (2,836 bp and 38 bp). Three families had deletions at D7S517, with each family having a different deletion (96 kb, 183 kb, and >69 kb). Another three families had deletions at D8S264, again with each family having a different deletion, ranging in size from <5.9 kb to >260 kb. At a fourth marker, D8S272, a 192-kb deletion was found in five families. Unrelated subjects and additional families without autism were screened for deletions at these four sites. Families screened included 40 families from Centre d'Etude du Polymorphisme Humaine and 28 families affected with learning disabilities. Unrelated samples were 299 elderly control subjects, 121 younger control subjects, and 248 subjects with Alzheimer disease. The deletion allele at D8S272 was found in all populations screened. For the other three sites, no additional deletions were identified in any of the groups without autism. Thus, these deletions appear to be specific to autism kindreds and are potential autism-susceptibility alleles. An alternative hypothesis is that autism-susceptibility alleles elsewhere cause the deletions detected here, possibly by inducing errors during meiosis.