Agreement Among Four Diagnostic Instruments for Autism Spectrum Disorders in Toddlers

Autistic spectrum disorders (ASD) can be difficult to diagnose in toddlers. This study compared diagnostic measures (ADOS-G, ADI-R, CARS, and clinical judgment using DSM-IV criteria) applied to toddlers. Results indicated that the ADOS-G, CARS, and clinical judgment agreed with each other but not with the ADI-R. Many of the children classified with ASD by the other measures were not classified with autism by the ADI-R because they did not display enough repetitive behaviors and stereotyped interests. These results indicate that young children with ASD may not display repetitive behaviors and stereotyped interests, and for toddlers, the ADI-R would have a higher sensitivity if revised to include a diagnosis of PDD-NOS, for which the requirement of repetitive behaviors is less stringent.     

The First Year Inventory: Retrospective Parent Responses to a Questionnaire Designed to Identify One-Year-Olds at Risk for Autism

The First Year Inventory (FYI) is a parent questionnaire designed to assess behaviors in 12-month-olds that suggest risk for an eventual diagnosis of autism. We examined the construct validity of the FYI by comparing retrospective responses of parents of preschool children with autism spectrum disorders (ASD; n = 38), other developmental disabilities (DD; n = 15), and typical development (TD; n = 40). Children with ASD were rated at significantly higher risk on the FYI than children with DD or TD. The DD group was at intermediate risk, also significantly higher than the TD group. These retrospective data strengthen the validity of the FYI and have implications for refining the FYI to improve its utility for prospective screening of 12-month-olds.     

Stability of the Autism Diagnostic Interview—Revised from Pre-School to Elementary School Age in Children with Autism Spectrum Disorders

This study examined the stability of scores on the ADI-R from pre-school to elementary school age in children with autism spectrum disorders (ASD). Participants were 35 children who, at T1, all had a clinical diagnosis of ASD. On initial assessment (mean age 3.5 years; SD 0.6 years), all met ADI-R algorithm criteria for autism. ADI-R assessments were repeated at follow up (FU; mean age 10.5 years; SD 0.8 years). Changes in ADI-R total, domain and ADI-R algorithm item scores were assessed. Twenty-eight children continued to score above the ADI-R cut-off for autism at FU, although significant decreases in ADI-R domain and item scores were also found. In conclusion while classification of children according to ADI-R criteria generally remained stable between pre-school and elementary school age, many children demonstrated significant improvements in symptom severity.     

Performance of the Social Communication Questionnaire in children receiving preschool special education services

To assess the performance of the Social Communication Questionnaire (SCQ) in identifying children with autism spectrum disorders (ASD), this study screened 268 children identified as receiving preschool special education services. Parent-reported ASD diagnosis, education department recorded autism special education classification, ADI-R autism, and ADOS autism and ASD were considered as alternative criterion measures of ASD diagnosis. The validity of the SCQ in this population was examined, with a special focus on examining alternative cut-points for indicating ASD. The predictive ability of the SCQ in this population was comparable to that reported for other samples. In addition, findings suggested that a cut-point below the recommended threshold would likely be useful for research studies seeking to identify ASD cases from the population of children receiving special education services. The cut-point selected for use in clinical settings may, however, differ.     

Chromosome 22q11 deletion syndrome and its relevance for child and adolescent psychiatry. An overview of etiology, physical symptoms, aspects of child development and psychiatric disorders

22q11.2 deletion syndrome is the most common interstitial deletion syndrome in humans. Patients with this syndrome can show a variety of somatic symptoms, especially characteristic facial abnormalities, heart defects, thymic hypo- or aplasia and velopharyngeal dysfunction with or without cleft palate. Disturbancies in motor, language, cognitive and social development are typical, as well as psychiatric disorders. Psychiatric disorders in children and adolescents are mostly attention-deficit/hyperactivity disorder, affective disorders, and autism spectrum problems. Schizophrenia in adults seems to be caused by 22q11.2 deletion in about 2% of all patients. We review current knowledge about etiology, physical features, developmental aspects and psychiatric comorbidity in 22q11.2 deletion syndrome as well as possible therapeutic interventions. Clinical criteria for genetic examinations on 22q11.2 deletion in children and adolescents with psychiatric disorders are defined. Until now 22q11.2 deletion is underdiagnosed in this population--despite of its clinical relevance.     

Brief Report: Excluding the ADI-R Behavioral Domain Improves Diagnostic Agreement in Toddlers

Past research shows poor agreement between the Autism Diagnostic Interview-Revised (ADI-R) and other diagnostic measures in toddlers. Our goal was to examine whether exclusion of the ADI-R behavioral domain results in improved diagnostic agreement. Toddlers aged 16–37 months (M = 26 months) received an evaluation because they failed the Modified Checklist for Autism in Toddlers (n = 142). Evaluations included the ADI-R, Autism Diagnostic Observation Schedule, Childhood Autism Rating Scale, and clinical judgment. Results found poor to fair agreement between the ADI-R and other measures; agreement improved when the ADI-R behavioral domain was excluded. These findings suggest that stereotyped interests and behaviors are not as relevant to the ADI-R as other diagnostic criteria when evaluating toddlers for autism spectrum disorders.     

Sex Differences in Diagnosis and Clinical Phenotypes of Chinese Children with Autism Spectrum Disorder

The aim of this study was to explore the differences between boys and girls in the diagnosis and clinical phenotypes of autism spectrum disorder (ASD) in China's mainland. Children diagnosed with ASD (n = 1064, 228 females) were retrospectively included in the analysis. All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). The results showed that girls scored significantly higher in ADI-R socio-emotional reciprocity than boys, and also scored lower in ADI-R and ADOS restricted and repetitive behaviors (RRBs). Meanwhile, the proportions of girls who satisfied the diagnostic cut-off scores in the ADI-R RRBs domain were lower than in boys (P < 0.05). Our results indicated that girls with ASD show greater socio-emotional reciprocity than boys. Girls also tended to show fewer RRBs than boys, and the type of RRBs in girls differ from those in boys. The ADI-R was found to be less sensitive in girls, particularly for assessment in the RRBs domain.     

Are special abilities in autism spectrum disorder associated with a distinct clinical presentation?

Special abilities may be common in autism spectrum disorders (ASD). The aim of this study was to investigate the clinical presentation of ASD with special abilities. Special abilities were defined based on the Autism Diagnostic Interview-Revised (ADI-R). Based on a sample of 398 children, ages 2–7 years old with ASD, 112 with special skills were compared to an age- and gender-matched group without special abilities (n = 79). The examined measures included autism symptoms severity, adaptive behaviors and head circumference percentile. Children with ASD and special abilities seemed to exhibit significantly less impaired ASD symptoms in the social, communication and stereotyped behaviors and significantly better adaptive skills than individuals with ASD without special skills. Children with ASD and special abilities had a larger head circumference percentile than children without special abilities. Special abilities occurred in 28% of the study participants. Memory skills were the most frequently reported special ability, followed by musical, visuospatial and reading skills. The authors conclude that individuals with ASD and special abilities might represent a distinct ASD subgroup with milder clinical ASD presentation. Larger head circumference in ASD was previously associated with enhanced “local” connectivity which provides detailed information processing and therefore might be related to the appearance of special abilities.     

Adolescents and Adults with Autism with and without Co-morbid Psychiatric Disorders: Differences in Maternal Well-Being

This study investigated the associations between the characteristics of adolescents and adults with autism spectrum disorders (ASD) and maternal well-being. Two groups were compared: mothers of adolescents and adults with ASD and co-morbid psychiatric disorders (n = 142) and mothers whose sons or daughters had a single diagnosis of ASD (n = 130). Individuals with co-morbid psychiatric disorders had higher levels of repetitive behaviors, asocial behavior, and unpredictability of behavior than their counterparts with ASD only. They also had poorer rated health as well as more frequent gastrointestinal problems and sleep problems. Mothers of sons and daughters with ASD and co-morbid psychiatric disorders reported higher levels of burden and a poorer quality parent-child relationship than mothers of sons and daughters with ASD only. Higher levels of asocial behavior, unpredictability of behavior, and poorer health in sons and daughters with ASD were predictive of greater burden in mothers and a poorer quality parent-child relationship.     

Effects of Child Characteristics on the Autism Diagnostic Interview-Revised: Implications for Use of Scores as a Measure of ASD Severity

The Autism Diagnostic Interview-Revised (ADI-R) is commonly used to inform diagnoses of autism spectrum disorders (ASD). Considering the time dedicated to using the ADI-R, it is of interest to expand the ways in which information obtained from this interview is used. The current study examines how algorithm totals reflecting past (ADI-Diagnostic) and current (ADI-Current) behaviors are influenced by child characteristics, such as demographics, behavioral problems and developmental level. Children with less language at the time of the interview had higher ADI-Diagnostic and ADI-Current. ADI-Diagnostic totals were also associated with age; parents of older children reported more severe past behaviors. Recommendations are provided regarding the use of the ADI-R as a measure of ASD severity, taking language and age into account.     

Response to Joint Attention in Toddlers at Risk for Autism Spectrum Disorder: A Prospective Study

Response to joint attention (RJA) is impaired in preschoolers with autism spectrum disorder (ASD) and is pivotal to social and communication development. Response to joint attention was examined at 14 and 24 months in 51 children at high risk for autism (siblings of children with autism). Outcome groups at age 3 years included ASD (n = 16), broader autism phenotype (n = 8), and non-broader autism phenotype (n = 27). The ASD group made minimal improvement in RJA between 14 and 24 months, but stability of RJA across tasks increased for all three groups. Significantly, lower RJA was observed for the ASD group at 24 months. Response to joint attention performance at 14 months predicted ASD outcome. Response to joint attention is an important screening and early intervention target.     

Parental report on socio-communicative behaviours in children with 22q11.2 deletion syndrome

Background Children with 22q11.2 deletion syndrome (22q11.2DS) are reported to have socio-communicative impairments. Although many of these children are diagnosed with intellectual disability (ID) and/or autism spectrum disorder (ASD), these populations are seldom used as control groups. Hence, information regarding syndrome-specific socio-communicative challenges is lacking.

Method Parental concerns regarding everyday communication were investigated by means of the Children’s Communication Checklist-2-NL (Geurts, 2007). Twenty children with 22q11.2DS (chronological age: 6 years–13 years 3 months) were compared to 21 children with idiopathic ID and 23 children with idiopathic ID and comorbid ASD. All groups were matched for fluid intelligence (Gf), chronological age, and core language scores.

Results Neglect or inadequate use of context information was more prevalent in children with 22q11.2DS than in children with idiopathic ID. Nonverbal communication seemed less impaired than in children with idiopathic ID + ASD.

Conclusion Pragmatic language skills and developmental trajectories in children with 22q11.2DS merit further investigation.     

The Relationship of Challenging Behaviors to Severity and Symptoms of Autism Spectrum Disorders

Challenging behaviors were assessed in 313 children, and it was demonstrated that children with autism spectrum disorders (ASD) exhibited greater levels of challenging behavior than both normally developing controls and children with psychopathology or atypical development. Next, we examined the relation between challenging behaviors and symptoms of autism in children with ASD. Severity of ASD was positively related to the number and intensity of challenging behaviors, and those with severe ASD exhibited significantly higher levels of problem behaviors than children with mild or moderate ASD. In addition, clusters of ASD symptoms were able to accurately predict endorsements of 8 of the 18 challenging behaviors assessed. Implications for the assessment and intervention of ASD and challenging behaviors are discussed.     

Adenosine A2A receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder

Autism spectrum disorders (ASDs) are heterogeneous disorders presenting with increased rates of anxiety. The adenosine A_2A receptor gene (ADORA2A) is associated with panic disorder and is located on chromosome 22q11.23. Its gene product, the adenosine A_2A receptor, is strongly expressed in the caudate nucleus, which also is involved in ASD. As autistic symptoms are increased in individuals with 22q11.2 deletion syndrome, and large 22q11.2 deletions and duplications have been observed in ASD individuals, in this study, 98 individuals with ASD and 234 control individuals were genotyped for eight single-nucleotide polymorphisms in ADORA2A. Nominal association with the disorder was observed for rs2236624-CC, and phenotypic variability in ASD symptoms was influenced by rs3761422, rs5751876 and rs35320474. In addition, association of ADORA2A variants with anxiety was replicated for individuals with ASD. Findings point toward a possible mediating role of ADORA2A variants on phenotypic expression in ASD that need to be replicated in a larger sample.     

Diagnostic Differentiation of Autism Spectrum Disorders and Pragmatic Language Impairment

The present study examined diagnostic differentiation between school-aged children with autism spectrum disorders (ASD) and children with pragmatic language impairment (PLI). Standardized diagnostic instruments were used to investigate the relationship between severity of ‘autism triad’ impairments and group membership. The Autism Diagnostic Observation Schedule was administered to 19 children with PLI and 22 children with ASD. Parents completed the Social Communication Questionnaire. There was a significant difference between diagnostic groups in the level of the severity of behaviors represented by the Communication and Reciprocal Social Interaction sub-domains on both diagnostic measures. Currently displayed Repetitive and Restricted Behaviors and Interests were not found to be useful for differentiating between groups. The similarities found between groups have important implications for intervention.     

Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome

Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. A potential role for immune dysfunction has been suggested in ASD. To test this hypothesis, we investigated evidence of differential cytokine release in plasma samples obtained from 2 to 5 year-old children with ASD compared with age-matched typically developing (TD) children and children with developmental disabilities other than autism (DD). Participants were recruited as part of the population based case-control CHARGE (Childhood Autism Risks from Genetics and Environment) study and included: 97 participants with a confirmed diagnosis of ASD using standard assessments (DSM IV criteria and ADOS, ADI-R), 87 confirmed TD controls, and 39 confirmed DD controls. Plasma was isolated and cytokine production was assessed by multiplex Luminex™ analysis. Observations indicate significant increases in plasma levels of a number of cytokines, including IL-1β, IL-6, IL-8 and IL-12p40 in the ASD group compared with TD controls (p < 0.04). Moreover, when the ASD group was separated based on the onset of symptoms, it was noted that the increased cytokine levels were predominantly in children who had a regressive form of ASD. In addition, increasing cytokine levels were associated with more impaired communication and aberrant behaviors. In conclusion, using larger number of participants than previous studies, we report significantly shifted cytokine profiles in ASD. These findings suggest that ongoing inflammatory responses may be linked to disturbances in behavior and require confirmation in larger replication studies. The characterization of immunological parameters in ASD has important implications for diagnosis, and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of ASD.     

Expression of autism spectrum and schizophrenia in patients with a 22q11.2 deletion

BackgroundCopy number variants (CNVs) associated with neuropsychiatric disorders are increasingly being identified. While the initial reports were relatively specific, i.e. implicating vulnerability for a particular neuropsychiatric disorder, subsequent studies suggested that most of these CNVs can increase the risk for more than one neuropsychiatric disorder. Possibly, the different neuropsychiatric phenotypes associated with a single genetic variant are really distinct phenomena, indicating pleiotropy. Alternatively, seemingly different disorders could represent the same phenotype observed at different developmental stages or the same underlying pathogenesis with different phenotypic expressions.AimsTo examine the relation between autism and schizophrenia in patients sharing the same CNV.MethodWe interviewed parents of 78 adult patients with the 22q11.2 deletion (22q11.2DS) to examine if autistic symptoms during childhood were associated with psychosis in adulthood. We used Chi-square, T-tests and logistic regression while entering cognitive level, gender and age as covariates.ResultsThe subgroup of 22q11.2DS patients with probable ASD during childhood did not show an increased risk for psychosis in adulthood. The average SRS scores were highly similar between those with and those without schizophrenia.ConclusionsASD and schizophrenia associated with 22q11.2DS should be regarded as two unrelated, distinct phenotypic manifestations, consistent with true neuropsychiatric pleiotropy. 22q11.2DS can serve as a model to examine the mechanisms associated with neuropsychiatric pleiotropy associated with other CNVs.     

Children with autism spectrum disorders and intellectual disability

PURPOSE OF REVIEW: The present article reviews the increasing literature on comorbidity, treatment and use of health service resources for children and adolescents with autism spectrum disorders and intellectual disability from January 2006 to January 2007. RECENT FINDINGS: Children and adolescents with autism spectrum disorders and intellectual disability have a high prevalence of attention-deficit/hyperactive disorder, mood disorders, catatonia and repetitive behaviours compared with children without autism. Psychopharmacology is effective in reducing symptoms of behavioural problems and attention-deficit/hyperactive disorder, although further studies are required. Autism spectrum disorders are recognized to occur with Smith-Lemli-Optiz syndrome and 22q11.2 deletion syndrome. Children and adolescents with autism spectrum disorders have a high use of mental health services. SUMMARY: There is increasing evidence of the comorbidity of psychiatric and behavioural disorders in young people with autism spectrum disorders and intellectual disability responding to established treatments. This high morbidity results in increased healthcare expenditure compared with children without autism and intellectual disability.     

L’ADI-R et l’ADOS face au diagnostic différentiel des troubles du spectre autistique : intérêts,limites et ouvertures

IntroductionCurrent developments in international public health are leading qualified authorities to release clinical practice guidelines for Autism Spectrum Disorders (ASD) assessment and diagnosis. Such documents incorporate procedures that rely on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) which are considered to be the “gold standard” assessment measures in the evaluation of ASD. Although these tools do prove their effectiveness in the evaluation of autistic symptomatology, they nevertheless stumble whenever the situation becomes more complex and reveal differential diagnostic issues in infantile and adult autism cases. This differential diagnostic issue remains significant in the clinical practice of daily life and has strong implications for the course of therapeutic treatment.ObjectivesOur objective is to underline and nuance the metrological qualities of the ADI-R and the ADOS in the differential diagnosis of autistic disorders by presenting a synthesis of recent studies, thus supporting the interest of maintaining an open debate on diagnostic practices.MethodsOur selective review of the recent literature focuses on studies that confront the ADI-R and the ADOS — used either independently or in a combination — with various differential issues in adulthood and childhood autism in order to highlight their qualities and limits.ResultsThe ADI-R is a semi-structured interview applied by trained examiners and applied to relatives and/or caregivers who collect developmental information about the patient's first years of life on a variety of behaviors and skills. It is therefore relatively dependent on the availability and personal bias of the interviewed third parties. Metric features highlighted by the reviewed studies straightforwardly reveal a certain effectiveness of the tool and a good discrimination of childhood disorders. At the same time, the tool's discriminatory capacity seems insufficient when applied to toddlers, very young children, and adults alike. The latter seems particularly true when it comes to differentiating between autistic and schizophrenic spectrum disorders. The ADOS is a semi-structured standardized observation assessment tool that has experienced several successive developments, such as optimizations concerning the sensitivity of its cutoffs. Many works have contributed to building such a tool with reliable and solid metric qualities which nevertheless retain important biases such as the subjectivity of the caregiver or the evaluator during the scoring process. For assessments of autistic children the tool still has a good diagnostic validity but seems to retain cases of incorrect diagnosis of ASD (false positives). In other words, disorders or developmental disabilities of some children and adolescents could not be distinguished from ASD when relying on this test alone. The ADOS Module 4, designed for the diagnosis of adolescents and adults with fluent speech, has undergone less updating. This revisited algorithm has metrological qualities useful for clinicians and remains one of the few available tools for this population. Unfortunately, its diagnostic accuracy is lower when applied to women, the elderly, people with personality disorders or higher intellectual abilities, or for the discrimination between ASD and schizophrenia. Overall, scores from these two instruments bring strong evidence of their usefulness in the diagnostic process of ASD, provided that they are used with caution and a critical clinical perspective, and only as a secondary technical support. Their use in combination is effective since they are complementary and compensate for each other's limitations. However, their globalized hegemony as “gold-standard” tools constitutes a setback insofar as it constrains the diagnosis of ASD to a set of stereotyped items. The latter in turn sets a normative model of autism that excludes other phenotypic forms, especially in the case of women and the elderly. Finally, the discrimination between autism and psychosis for children seems to remain an insoluble task even for the ADI-R/ADOS combination.ConclusionsThe problematics of differential diagnosis remain critical for clinical approaches to autism. Therefore, formalizations of the diagnostic procedures must be able to remain open-minded and accompanied by a creative clinical approach, especially in the case of complex situations that are not soluble by means of conventional diagnostic tools. One possibility may lie in the deepening of the phenomenological approach to autism as an attempt to model the subjective phenomena of autistic subjects and thus operationalize elements that serve the diagnostic process. In the same way, a psychodynamic epistemology could help clinicians to go beyond the consideration of observable behaviors and scores, introducing a psychoanalytic point of view that interfaces objective behaviors with the individual's dynamic intrapsychic functioning. This project could be articulated with projective methodologies — notably the Rorschach test — which respects the needs for standardization and quantification of conventionally used diagnostic tools.     

The identification and measurement of autistic features in children with septo-optic dysplasia,optic nerve hypoplasia and isolated hypopituitarism

This study aimed to highlight the occurrence of autism spectrum disorders (ASDs) in children with septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH). A cross-sectional study was designed, including 28 children with SOD and 14 children with ONH. Clinician diagnosis of ASD was reported in 14 children. The Social Communication Questionnaire (SCQ) reported that 23 children met the cut-off point for ASD, and 9 children met the cut-off point for autism. Greater levels of intellectual disability and visual loss were reported in children with ASD in comparison to those without ASD, but, of the two, intellectual disability was a better predictor for ASD. The SCQ lost its sensitivity and specificity in children who had greater visual loss which highlights a requirement for a measure that is sensitive to visual loss. It is also recommended that children with SOD/ONH would benefit from routine screening for ASDs.