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Regional brain chemical alterations in young children with autism spectrum disorder.

OBJECTIVE: The authors evaluated regional brain chemistry for evidence of increased neuronal packing density in autism. METHODS: Forty-five 3- to 4-year-old children with autism spectrum disorder (ASD), 13 children with typical development (TD), and 15 children with delayed development (DD) were studied using dual-echo proton echoplanar spectroscopic imaging (32 x 32 matrix-1 cm(3) voxels) to measure brain chemical concentrations and relaxation times. Chemical quantification was corrected for tissue partial volume and relative measures of chemical relaxation (T(2r)) were calculated from the paired echoes. Measures from averaged and individual regions were compared using analysis of variance corrected for multiple comparisons. RESULTS: ASD subjects demonstrated reduced N-acetylaspartate (NAA) (-10%), creatine (Cre) (-8%), and myo-inositol (-13%) concentrations compared to TD controls and prolonged NAA T(2r) relative to TD (7%) and DD (9%) groups. Compared to DD subjects, children with ASD also demonstrated prolonged T(2r) for choline (10%) and Cre (9%). Regional analyses demonstrated subtle patterns of chemical alterations in ASD compared to the TD and DD groups. CONCLUSIONS: Brain chemical abnormalities are present in ASD at 3 to 4 years of age. However, the direction and widespread distribution of these abnormalities do not support hypothesis of diffuse increased neuronal packing density in ASD.

Age Distribution↗

Early indicators of autism spectrum disorders in the second year of life.

Three groups of 18 children were selected for this study, one group with autism spectrum disorders (ASD), one group with developmental delays in which ASD was ruled out (DD), and one group with typical development (TD), from a pool of 3026 children who were screened with the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP, Wetherby & Prizant. 2002) Infant-Toddler Checklist under 24 months of age. The CSBS DP Behavior Sample was videotaped on selected children as a second-level evaluation during the second year of life. The Infant-Toddler Checklist had a sensitivity and specificity of 88.9% for this sample of children. Significant group differences were found on the Infant-Toddler Checklist and the Behavior Sample, however, these differences did not distinguish children with ASD and DD with high accuracy. The videotapes of the Behavior Sample were reanalyzed to identify red flags of ASD. Nine red flags differentiated children in the ASD group from both the DD and TD groups and four red flags differentiated children in the ASD Group from the TD group but not the DD group. These 13 red flags were found to discriminate the three groups with a correct classification rate of 94.4%.

Age Factors↗

A comparison of motor delays in young children: autism spectrum disorder, developmental delay, and developmental concerns.

This study assessed motor delay in young children 21-41 months of age with autism spectrum disorder (ASD), and compared motor scores in children with ASD to those of children without ASD. Fifty-six children (42 boys, 14 girls) were in three groups: children with ASD, children with developmental delay (DD), and children with developmental concerns without motor delay. Descriptive analysis showed all children with ASD had delays in gross motor skills, fine motor skills, or both. Children with ASD and children with DD showed significant impairments in motor development compared to children who had developmental concerns without motor delay. Motor scores of young children with ASD did not differ significantly on motor skill measures when compared to young children with DD.

Autistic Disorder↗

The validity of using self-reports to assess emotion regulation abilities in adults with autism spectrum disorder.

PURPOSE: The current paper focused on the validity of using self-reports to assess emotion regulation abilities in autism spectrum disorders (ASD). To assess this we sought responses to two alexithymia self-reports and a depression self-report at two time points from adults with and without ASD. MATERIALS AND METHODS: An initial sample of 27 adults with ASD and 35 normal adults completed the 20-item Toronto alexithymia scale (TAS-20), the Bermond and Vorst alexithymia questionnaire-form B (BVAQ-B), and the Beck depression inventory (BDI), at test time 1. Of these individuals, 19 ASD and 29 controls participated again after a period ranging from 4 to 12 months. RESULTS: ASD participants were able to report about their own emotions using self-reports. BVAQ-B showed reasonable convergent validity and test-retest reliability in both groups. Scores on both alexithymia scales were stable across the two participant groups. However, results revealed that although the TAS-20 total score discriminated between the two groups at both time points, the BVAQ-B total score did not. Moreover, the TAS-20 showed stronger test-retest reliability than the BVAQ-B. CONCLUSION: ASD participants appeared more depressed and more alexithymic than the controls. The use of the BVAQ-B, as an additional assessment of alexithymia, indicated that ASD patients have a specific type of alexithymia characterised by increased difficulties in the cognitive domain rather than the affective aspects of alexithymia.

Adult↗

Congenital anomalies associated with autism spectrum disorders.

This study examined whether major congenital structural anomalies identified in infancy occurred more frequently in children later diagnosed with autism spectrum disorders (ASD; n=417; 341 males, 76 females) than in comparison children (n=2,067; 1,681 males, 386 females). Participants were sampled from infants born at Kaiser Permanente Northern California facilities between 1995 and 1999 who remained health plan members for at least 2 years (n=88,163). Comparison children were frequency-matched to children with ASD according to sex, birth year, and birth hospital. Congenital anomalies were diagnosed in 10.8% of children with ASD and 6.2% of comparison children (crude odds ratio [ORc] 1.8, 95% confidence interval [CI] 1.3-2.6). This association remained significant after adjustment for key maternal and infant covariates (adjusted OR [ORa] 1.7, 95% CI 1.1-2.4). Almost all organ-system anomaly categories were more prevalent in children with ASD, however only gastrointestinal anomalies were significantly associated with ASD in adjusted analyses (1.9 vs 0.4%, ORa 5.1, 95% CI 1.8-14.1).

Abnormalities, Multiple↗

Association between restricted and repetitive behaviors and nonverbal IQ in children with autism spectrum disorders.

The present study explored the relationship between nonverbal IQ and restricted and repetitive behaviors (RRBs) in 830 children with Autism Spectrum Disorders. The role of chronological age as a moderator of this relationship was also investigated. For many behaviors, there was a significant interaction between nonverbal IQ and chronological age, such that nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children. For the majority of such behaviors (e.g. repetitive use of objects, hand and finger mannerisms), RRB prevalence was negatively associated with NVIQ. However, the prevalence of certain behaviors (e.g. circumscribed interests) showed positive relationships with NVIQ, which provides some support for the idea of different classes of RRBs. For the severity of different RRBs, there were several significant effects for age and NVIQ, but few interactions.

Age Factors↗

Evidence for allelic association on chromosome 3q25-27 in families with autism spectrum disorders originating from a subisolate of Finland.

Recent molecular studies on autism and related disorders have supported a multilocus etiology for the disease spectrum. To maximize genetic and cultural homogeneity, we have focused our molecular studies to families originating from a subisolate of Central Finland. Genealogical studies enabled the identification of a megapedigree comprising of 12 core families with autism and Asperger syndrome (AS). We analyzed two chromosomal regions on Iq and 3q showing highest lod scores in our genome-wide scan, as well as the AUTS1 locus on chromosome 7q. For markers on 3q25-27, more significant association was observed in families from subisolate compared to families from the rest of Finland. In contrast, no clear evidence for association on AUTS1 locus was obtained. The wide interval showing association, in particular, on chromosome 3q suggests a locus for autism spectrum of disorders on this chromosomal region.

Asperger Syndrome↗

Is there a 'regressive phenotype' of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA Study.

A multi-site study of 351 children with Autism Spectrum Disorders (ASD) and 31 typically developing children used caregiver interviews to describe the children's early acquisition and loss of social-communication milestones. For the majority of children with ASD who had experienced a regression, pre-loss development was clearly atypical. Children who had lost skills also showed slightly poorer outcomes in verbal IQ and social reciprocity, a later mean age of onset of autistic symptoms, and more gastrointestinal symptoms than children with ASD and no regression. There was no evidence that onset of autistic symptoms or of regression was related to measles-mumps-rubella vaccination. The implications of these findings for the existence of a 'regressive phenotype' of ASD are discussed.

Autistic Disorder↗

Factor analysis of the aberrant behavior checklist in individuals with autism spectrum disorders.

Exploratory factor analysis (varimax and promax rotations) of the aberrant behavior checklist-community version (ABC) in 275 individuals with Autism spectrum disorder (ASD) identified four- and five-factor solutions which accounted for >70% of the variance. Confirmatory factor analysis (Lisrel 8.7) revealed indices of moderate fit for the five-factor solution. Our results suggest that the factor structure of the ABC is robust within an ASD sample. Both solutions yielded a three items self-injury factor. Stratifying on this factor, we identified significant differences between the high- and low-self injury groups on ABC subscales. The emergence of a self-injury factor, while not suggestive of a new subscale, warrants further exploration as a tool that could help dissect relevant neurobiobehavioral groups in ASD.

Adolescent↗

A variant Cri du Chat phenotype and autism spectrum disorder in a subject with de novo cryptic microdeletions involving 5p15.2 and 3p24.3-25 detected using whole genomic array CGH.

Cri du Chat syndrome (CdCs) is a well-defined clinical entity, with an incidence of 1/15,000 to 1/50,000. The critical region for CdCs has been mapped to 5p15, with the hallmark cat-like cry sublocalized to 5p15.3 and the remaining clinical features to 5p15.2. We report findings in a subject with a de novo t(5;7)(p15.2;p12.2) and an inv(3)(p24q24), who was found to have a cryptic microdeletion in the critical region for CdCs detected using a 1-Mb genomic microarray. In addition to 5p deletion, the proband had a de novo single clone loss at the 3p breakpoint of inv(3)(p24q24) and a familial single clone deletion at 18q12. Deletions were confirmed using microsatellite analysis and fluorescence in situ hybridization. The 5p deletion encompasses approximately 3 Mb, mapping to the border between bands 5p15.2 and 5p15.31. The single clone deletion on chromosome 3 maps to 3p24.3-3p25, for which there is no known phenotype. The clinical features of our proband differ from the characteristic CdC phenotype, which may reflect the combined effect of the two de novo microdeletions and/or may further refine the critical region for CdCs. Typical features of CdCs that are present in the proband include moderate intellectual disability, speech, and motor delay as well as dysmorphic features (e.g. broad and high nasal root, hypertelorism, and coarse facies). Expected CdCs features that are not present are growth delay, microcephaly, round facies, micrognathia, epicanthal folds, and the signature high-pitched cry. Behavioral traits in this subject included autism spectrum disorder, attention-deficit hyperactivity disorder, and unmanageable behavior including aggression, tantrums, irritability, and self-destructive behavior. Several of these behaviors have been previously reported in patients with 5p deletion syndrome. Although most agree on the cat-cry critical region (5p15.3), there is discrepancy in the precise location and size of the region associated with the more severe manifestations of CdCs. The clinical description of this proband and the characterization of his 5p deletion may help to further refine the phenotype-genotype associations in CdCs and autism spectrum disorder.

Adolescent↗

Repetitive behaviour and play in typically developing children and children with autism spectrum disorders.

The view of a triad of impairments [(Wing and Gould (1979). Journal of Autism and Developmental Disorders, 9, 11-30] in which impaired imagination is linked with repetitive behaviour is widely accepted. However this categorisation differs from the international classification systems, which link imagination to communication impairments rather than to repetitive behaviours. To investigate this relationship, the Activities and Play Questionnaire-Revised was completed by 196 parents of 2-8-year-old children with autism spectrum disorders (ASD) and typical development. Results showed that repetitive behaviours were associated with play in ASD but not in typical development, supporting Wing and Gould's triad. However there was also an association between play, repetitive behaviour and language, confirming the international classification systems description of imagination as a component of language and communication difficulties.

Autistic Disorder↗

Autism spectrum disorder screening and management practices among general pediatric providers.

It is unclear to what extent general developmental/behavioral assessments are performed, if screening for autism spectrum disorders (ASDs) is being conducted, and what the barriers to providing such assessments are in routine pediatric practice. Therefore, this study examines (1) the factors influencing the use of general developmental and autism-specific screening tools in primary care pediatric practice, (2) the barriers to providing these assessments, and (3) pediatricians' beliefs regarding ASD prevalence. A cross-sectional survey was mailed in June 2004 to a 60% (n = 1119) random sample of Maryland and Delaware licensed pediatricians. In August 2004, a second mailing was sent to non-respondents. A total of 471 (42%) of the surveys were returned, and of those, 255 (54%) who practiced in general primary care were eligible. The sample was 47% male, 69% had more than 14 years' experience, 71% were in private practices, and 56% had fewer than 10 ASD patients. Most (82%) routinely screened for general developmental delays, but only 8% screened for ASD. The main reasons reported for not screening for ASD were lack of familiarity with tools (62%), referred to a specialist (47%), or not enough time (32%). Most specialist referrals (77%) were to a developmental pediatrician. Most pediatricians (71%) believed that ASD prevalence has increased, and nearly all attributed this to changes in diagnostic criteria and treatment. Service system limitations must be overcome to increase awareness and familiarity with screening tools, provide sufficient time and resources, improve screening, and enhance provider education.

Adult↗

Developing an information pack for the Asian carers of people with autism spectrum disorders.

An investigation is described which forms the basis for the development of an information package for the Asian carers of people with autism spectrum disorders (ASD) and learning disabilities. The results of semi-structured interviews and planning for questionnaires with three different linguistic Asian groups (Urdu, Gujarati and Bengali) are presented. The views, attitudes and awareness of autism, knowledge of support services and perceived priority of needs are analysed for the three different communities. The investigation concludes with recommendations as to whether separate information is needed by each culture or whether a single information pack can be used and presented in each language format. The possible presentation format in which the information can be produced is also discussed.

Asia↗

Educational placements and service use patterns of individuals with autism spectrum disorders.

This project was undertaken to identify child characteristics associated with educational placement and service use in high-functioning children with autism spectrum disorders. The sample of 101 (nine females) had a mean age of 12 +/- 3 years (mean IQ = 101.77 +/- 19.50). Results indicate that lower-cognitive ability and communication skill were associated with placement in special education. Based on parent-report, most students stayed in the same placement (regular or special education) in which they began first grade and the majority of students received special services in their schools (most often speech/language intervention). Findings highlight the emphasis placed on certain child characteristics (e.g., cognitive ability), with far less emphasis on other areas (e.g., degree of social deficit), in educational placement and service provision.

Adolescent↗

Determining treatment outcome in early intervention programs for autism spectrum disorders: a critical analysis of measurement issues in learning based interventions.

One of the areas receiving the greatest attention from researchers studying autism spectrum disorders in recent years involves psychologically based early intervention programs. Various claims of cure, marked improvement in social and communication skills, and improved I.Q. are among the conclusions that have been drawn by various researchers. However, little has been done to analyze the dependent variables used in these studies and their impact on the conclusions reached regarding treatment effectiveness. Obviously, this set of measures is crucial since these methods define which behaviors "improved" and to what extent. The present review analyzes the current status, strengths, and weaknesses of these measurements.

Autistic Disorder↗

Language play in children with autism spectrum disorders: implications for practice.

The purpose of this article is to present evidence for the use of language play by children with autism spectrum disorders (ASD) within the context of play with peers. A conceptual framework for the development of language play is described. This framework, which is supported by the literature on language play in typically developing children, is used to assess patterns of language play in children with ASD. The findings of a descriptive study are used to provide evidence for language play in the speech of children with ASD during interactions with typical peers and show that children with ASD use language play in a similar way as their typically developing peers with the exception of age of occurrence. Implications for clinicians in their work with children with ASD are discussed as they relate to the existence of language play in children with ASD and the function of language play as a tool for language learning.

Autistic Disorder↗

Practitioner review: Diagnosis of autism spectrum disorder in 2- and 3-year-old children.

BACKGROUND: Progress has recently been made in the earlier identification of children with autism spectrum disorder (ASD). Whilst being welcome, this progress to earlier referral and diagnosis presents new challenges to clinical practice, including the accuracy and stability of early diagnosis, the utility of standardised assessment instruments with young pre-schoolers and the ability to indicate prognosis. METHOD: A selective review of recent research literature on the characteristic features of ASD in preschool children. RESULTS: Multidisciplinary diagnostic assessment should include detailed information on developmental history, parents' descriptions of the everyday behaviour and activities of the child, direct assessment of the child's social interaction style, including where possible with age peers, and formal assessment of communicative, intellectual and adaptive function. Clinical assessments need to concentrate on the identification of impairments in early non-verbal social communication behaviours that characterise children with ASD from the second year of life, including social orienting, joint attention, imitation, play and reciprocal affective behaviour. The particular pattern of symptoms that presents in a 2-year-old with ASD may differ from that seen at the more prototypic age of 4 or 5 years. In particular, overt repetitive and stereotyped behaviours may be less notable, although where these are seen alongside the social and communicative impairments they are highly indicative of ASD. The use of standardised assessment instruments and the strict application of the DSM and ICD diagnostic criteria need to be employed with caution, as an expert clinical view has been shown to be more accurate. An important aspect of early diagnostic consultation is an open and straightforward approach to the negotiation of the diagnostic view with parents over time. CONCLUSIONS: Earlier diagnosis and rising recognition of ASD have significant implications for primary healthcare and specialist diagnostic and therapeutic services.

Autistic Disorder↗