Does Parent Report of Behavior Differ Across ADOS-G Classifications: Analysis of Scores from the CBCL and GARS

Behavior checklists are often utilized to screen for Autism Spectrum Disorders (ASDs) when comprehensive evaluations are unfeasible. The usefulness of two behavioral checklists, the Gilliam Autism Rating Scale (GARS) and Child Behavior Checklist (CBCL), in identifying ASDs was investigated among 109 children with Autism, 32 children with ASD, and 51 Non-Spectrum children based on Autism Diagnostic Observation Schedule-Generic classifications. The GARS did not distinguish children with ASDs from those without. The Withdrawn and Pervasive Developmental Problems subscales of the CBCL were higher among children with Autism than among Non-Spectrum children. These CBCL subscales also had better sensitivity and specificity in identifying children with Autism than the GARS. Results suggest that the CBCL is a useful behavioral checklist for screening ASDs.     

The screen for social interaction (SSI): a screening measure for autism spectrum disorders in preschoolers

We report on the preliminary validity and utility of the Ghuman-Folstein Screen for Social Interaction (SSI), a measure of social interaction that can serve to screen for autism spectrum disorders (ASDs) in clinical samples of young high-risk children. Caregivers of 350 children (176 younger participants, ages 24-42 months, mean age = 34.1 months; and 174 older participants, ages 43 to 61 months, mean age = 52.4 months) with ASDs, non-ASD developmental and/or psychiatric disorders, or without developmental concerns completed the SSI. A series of analyses resulted in shortened versions of the SSI: a 26-item SSI-Younger (SSI-Y) and a 21-item SSI-Older (SSI-O) version. The SSI-Y and SSI-O showed moderate convergence with ASD diagnostic measures and significantly differentiated ASD and non-ASD clinical groups. Sensitivity and specificity values for discriminating ASD and non-ASD clinical participants were 0.87 and 0.71, respectively for the SSI-Y and 0.81 and 0.70, respectively for the SSI-O. Scoring recommendations were made based on the ROC results.     

Disparity in autism spectrum disorder prevalence among Taiwan National Health Insurance enrollees: Age, gender and urbanization effects

The present study aims to characterize the prevalence of autism spectrum disorders (ASDs) in Taiwan while examining the effects of age, gender, and urbanization on ASD occurrence. A cross-sectional study was conducted to analyze data from 895,639 random health insurance claimants who claimed medical services in the year 2007. Autism was defined using the ICD-9-CM Diagnosis Code 299.0 (autism, current or active). The prevalence of autistic cases was found to be 12.3‰ (10,868/884,771) in the general population, with the prevalence among males (19.2‰) significantly higher than that among females (6‰). With regards to age distribution, we found that the autistic group (mean age = 16.0 years) was significantly younger than the general population (mean age = 37.2 years). A logistic regression analysis found that age, gender, residence urbanization level and Bureau of National Health Insurance regional division all constituted influence factors for autistic occurrence. The results demonstrate the importance of taking into account age, gender, and geographical disparities in autistic prevalence in order to implement appropriate public health policies for the ASD population.     

Autoantibodies to cerebellum in children with autism associate with behavior

Autism is a heterogeneous disorder with a poorly understood biological basis. Some children with autism harbor plasma autoantibodies that target brain proteins. Similarly, some mothers of children with autism produce antibodies specific to autism that target pairs of fetal brain proteins at 37/73 and 39/73 kDa. We explored the relationship between the presence of brain-specific autoantibodies and several behavioral characteristics of autism in 277 children with an autism spectrum disorder and 189 typically developing age-matched controls. Further, we used maternal autoantibody data to investigate potential familial relationships for the production of brain-directed autoantibodies. We demonstrated by Western blot that autoantibodies specific for a 45 kDa cerebellar protein in children were associated with a diagnosis of autism (p = 0.017) while autoantibodies directed towards a 62 kDa protein were associated with the broader diagnosis of autism spectrum disorder (ASD) (p = 0.043). Children with such autoantibodies had lower adaptive (p = 0.0008) and cognitive function (p = 0.005), as well as increased aberrant behaviors (p < 0.05) compared to children without these antibodies. No correlation was noted for those mothers with the most specific pattern of anti-fetal brain autoantibodies and children with the autoantibodies to either the 45 or 62 kDa bands. Collectively, these data suggest that antibodies towards brain proteins in children are associated with lower adaptive and cognitive function as well as core behaviors associated with autism. It is unclear whether these antibodies have direct pathologic significance, or if they are merely a response to previous injury. Future studies are needed to determine the identities of the protein targets and explore their significance in autism.     

Relationship between the social functioning of children with autism spectrum disorders and their siblings’ competencies/problem behaviors

There is very little known about how sibling characteristics may influence the social functioning of a child with an autism spectrum disorder (ASD). The current study utilized data from the Simons Simplex Collection (SSC; n = 1355 children with ASD and 1351 siblings) to investigate this relationship. Phenotypic measures included (a) the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS), and the Vineland Adaptive Behavior Scales-II (VABS-II) for the probands with ASD and (b) the Social Communication Questionnaire (SCQ), the Social Responsiveness Scale (SRS), the Child Behavior Checklist (CBCL), and the VABS-II for siblings. Sibling data were first analyzed collectively, then analyzed by “older” and “younger” groups, relative to the age of the proband with ASD. Significant correlations were observed between probands’ and siblings’ VABS-II socialization domain scores; additional associations were noted between (a) probands’ VABS-II socialization domain scores and siblings’ CBCL internalizing subscale scores when only younger siblings were analyzed, and (b) probands’ ADOS Reciprocal Social Interaction (RSI) domain scores and the sibling SCQ scores when only older siblings were analyzed. These findings suggest that typically developing children may have a small yet meaningful influence on the prosocial development of their siblings with ASD. Limitations and future directions are discussed.     

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.     

Depression and Anxiety Symptoms in Children and Adolescents with Autism Spectrum Disorders without Intellectual Disability

Recent studies have shown that rates of depression and anxiety symptoms are elevated among individuals with autism spectrum disorders (ASDs) of various ages and IQs and that depression/anxiety symptoms are associated with higher IQ and fewer ASD symptoms. In this study which examined correlates of depression and anxiety symptoms in the full school-age range of children and adolescents (age 6-18) with ASDs and IQs ≥ 70 (n = 95), we also observed elevated rates of depression/anxiety symptoms, but we did not find higher IQ or fewer ASD symptoms among individuals with ASDs and depression or anxiety symptoms. These findings indicate an increased risk for depression/anxiety symptoms in children and adolescents with ASDs without intellectual disability, regardless of age, IQ, or ASD symptoms.     

Autoantibodies against neuronal progenitors in sera from children with autism

The pathological role of autoantibodies in development of CNS disorders is a new idea with growing interest among neuroscientists. The involvement of autoimmune response in the pathogenesis of autism spectrum disorders (ASD) has been suggested by the presence of multiple brain-specific autoantibodies in children with ASD and in their mothers. The possibility of the effect of autoimmunity on neurogenesis and postnatal brain plasticity has not been determined. The presence of autoantibodies against human neuronal progenitor cells (NPCs) stimulated for neuronal differentiation in culture was tested in sera from children with autism (n = 20) and age-matched controls (n = 18) by immunoblotting and immunocytochemistry. Immunoreactivity against multiple NPCs proteins of molecular sizes of approximately 55 kDa, 105 kDa, 150 kDa, and 210 kDa in sera from individuals with autism had a higher incidence and was stronger than in control sera which immunoreacted mainly with a 150 kDa protein. The sera from children with autism immunoreacted the strongest with NPCs expressing neuronal markers Tuj1 and doublecortin, but not astrocyte marker GFAP. The epitopes recognized by antibodies from sera were not human-specific because they detected also NPCs in situ in murine hippocampus. The autoimmune reactions against NPCs suggest an impaired tolerance to neural antigens in autism. These autoantibodies may be symptomatic for autism and furthermore, their presence suggests that autoimmunity may affect postnatal neuronal plasticity particularly after impairment of blood–brain barrier. Future studies will determine the diagnostic value of the presence of autoantibodies in autism and the therapeutic value of prevention of autoimmunity in autism.     

Autism-specific maternal autoantibodies recognize critical proteins in developing brain

Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45–405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.     

Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders

Autism spectrum disorders (ASD) are a group of heterogeneous, behaviorally defined disorders characterized by disturbances in social interaction and communication, often with repetitive and stereotyped behavior. Previous studies have described the presence of antibodies to various neural proteins in autistic individuals as well as post-mortem evidence of neuropathology in the cerebellum. We examined plasma from children with ASD, as well as age-matched typically developing controls, for antibodies directed against human cerebellar protein extracts using Western blot analysis. In addition, the presence of cerebellar specific antibodies was assessed by immunohistochemical staining of sections from Macaca fascicularis monkey cerebellum. Western blot analysis revealed that 13/63 (21%) of subjects with ASD possessed antibodies that demonstrated specific reactivity to a cerebellar protein with an apparent molecular weight of approximately 52 kDa compared with only 1/63 (2%) of the typically developing controls (p=0.0010). Intense immunoreactivity, to what was determined morphologically to be the Golgi cell of the cerebellum, was noted for 7/34 (21%) of subjects with ASD, compared with 0/23 of the typically developing controls. Furthermore, there was a strong association between the presence of antibodies reactive to the 52 kDa protein by Western blot with positive immunohistochemical staining of cerebellar Golgi cells in the ASD group (r=0.76; p=0.001) but not controls. These studies suggest that when compared with age-matched typically developing controls, children with ASD exhibit a differential antibody response to specific cells located in the cerebellum and this response may be associated with a protein of approximately 52 kDa.     

Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73 kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73 kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement.     

An Initial Psychometric Evaluation of the CBCL 6-18 in a Sample of Youth with Autism Spectrum Disorders

Individuals with an autism spectrum disorder (ASD) often present with co-occurring emotional and behavioral disorders (EBD). The Child Behavior Checklist 6-18 (CBCL; Achenbach & Rescorla, 2001) is an EBD measure that contains several norm-referenced scales derived through factor analysis of data from the general pediatric population. The psychometric properties of this widely used and well-researched measure have not been evaluated in samples of youth with ASD. This study evaluated the CBCL's internal structure, scale reliability, criterion-related validity, and diagnostic accuracy using archival data from a well-characterized sample of youth with ASD (N = 122). Confirmatory factor analyses supported the unidimensionality of the CBCL's syndrome scales and its internalizing-externalizing factor structure. Significance tests indicated that many scales discriminated between two subgroups: a group of individuals with ASD + EBD and a group with ASD alone. Diagnostic accuracy analyses indicated that the CBCL had good sensitivity but low specificity for detecting co-occurring disorders. Results supported the use of the CBCL in conjunction with other clinical data when assessing for EBD in youth with ASD.     

Rôle de la flexibilité cognitive dans la reconnaissance d’expressions émotionnelles chez les personnes atteintes de Troubles du Spectre Autistique

The present research tested whether young children with Autism Spectrum Disorders (ASDs) shows impaired recognition of basic-emotion expressions (anger, fear, happiness, sadness, disgust) and the same emotions embedded in a social background (i.e. simple versus complex facial emotion recognition), compared with typically developing (TD) children. Moreover, we investigated whether cognitive flexibility could be linked with these faces processing skills. Our results showed that performance in ASD children was similar to the group of TD children for simple emotion recognition whereas TD children outperformed ASDs children in the complex task. In the second part, our study tends to confirm a link between cognitive flexibility and faces processing skills in children with ASD, especially when different contextual cues are present to extract facial emotion. We confirm previous findings demonstrating that individuals with ASDs use an effortful “systematizing” process to recognize emotion expressions, whereas TD individuals use a more holistic process. These results are discussed within the context of current neuropsychological studies on “weak central coherence”, hyper-systemizing theory, and lack of cognitive flexibility in ASD.     

Identification of Autism Spectrum Disorders Using the Child Behavior Checklist in Singapore

We tested the ability of the 2001 CBCL syndromes to discriminate among 86 children with Autism Spectrum Disorder (ASD), 117 children with Attention Deficit Hyperactivity Disorder—Inattentive type, 426 children with Attention Deficit Hyperactivity Disorder—Hyperactive-Impulsive or Combined type, 200 clinically referred children who did not receive a diagnosis, and 436 typically-developing children in a community sample. The Withdrawn/Depressed, Social Problems, and Thought Problems syndromes significantly discriminated the ASD group from the four other groups. An ASD scale, constructed from nine CBCL items, demonstrated moderate to high sensitivity (68 to 78%) and specificity (73 to 92%). Consistent with previous research, findings from this study provide strong support for the CBCL as a screening tool for ASD.     

Psycholinguistic abilities of children with Williams syndrome

The objective of this study was to investigate the psycholinguistic abilities of children with Williams syndrome (WS) and typically developing children using the Illinois Test of Psycholinguistic Abilities (ITPA). Performance on the ITPA was analysed in a group with WS (N = 20, mean age = 8.5 years, SD = 1.62) and two typically developing groups, matched in mental (MA, N = 20, mean age = 4.92 years, SD = 1.14) and chronological age (CA, N = 19, mean age = 8.35 years, SD = 3.07). Overall, within-group analyses showed that individuals with WS displayed higher scalar scores on the visual reception and visual association subtests. When groups were compared, we observed inferior performance of the WS group on all ITPA subtests when compared with typically developing groups. Moreover, an interaction between reception and group was found, only the WS group demonstrated superior performance on the visual reception subtest when compared to the auditory reception subtest. Evidence from this study offers relevant contributions to the development of educational intervention programs for children with WS.     

Abnormalities of joint mobility and gait in children with autism spectrum disorders

Aims: Abnormalities of gross motor function in children with autism are well known to clinicians but have not received much empirical documentation and, with the exception of stereotypies, are not among its diagnostic criteria. We recorded the characteristics of gait and prevalence of toe walking, the range of passive joint mobility, and age at walking in children with DSM IV autism spectrum disorders (ASDs) and in age- and gender-matched typically developing peers (mean age 4 years 6 months, range 22 months–10 years 9 months). Methods: We evaluated maximum range of mobility at the elbow, wrist, metacarpo–phalangeal, and ankle joints and videoed children walking and running. Two neurologists blind to diagnosis independently scored features of gait clinically. Results: Children with ASDs had significantly greater joint mobility (p < .002), more gait abnormalities (p < .0001), and on average walked 1.6 months later than their non-autistic peers. Interpretation: This study indicates that attention should be directed to motor abnormalities as well as sociability, communication, and restricted and repetitive behaviors in individuals with ASDs. Motor deficits add to children’s other handicaps. They indicate that ASDs affect a broader range of central nervous system circuitry than often appreciated.     

Child Behavior Check List 1½–5 as a tool to identify toddlers with Autism Spectrum Disorders: A case-control study

Tools to identify toddlers with autism in clinical settings have been recently developed. This study evaluated the sensitivity and specificity of the Child Behavior Check List 1½–5 (CBCL 1½–5) in the detection of toddlers subsequently diagnosed with an Autism Spectrum Disorder (ASD), ages 18–36 months. The CBCL of 47 children with ASD were compared to the CBCL of 47 toddlers with Other Psychiatric Disorders (OPD) as well as the CBCL of 47 toddlers with Typical Development (TD) in a case control study. One-way analysis of variance (ANOVA) and logistic regression with odds ratio (OR) analyses were performed. In order to establish the optimal threshold able to discriminate children with ASD from children with OPD and TD, Receiver Operating Characteristic (ROC) analyses were performed. One-way ANOVA revealed significant differences between the three groups. Logistic regression analysis showed that the Withdrawn and the Pervasive Developmental Problems (PDP) subscales can recognize toddlers subsequently identified as ASD from both children with TD (p < 0.001) and OPD (p < 0.001). ROC analyses showed very high sensitivity and specificity for the PDP (0.98 and 0.91) and Withdrawn (0.92 and 0.97) subscales when ASD was compared to TD. Sensitivity and specificity of Withdrawn (0.90 and 0.83) and PDP (0.85 and 0.83) remained high when comparing ASD versus OPD. In conclusion, the CBCL 1½–5 seemed to be able to identify toddlers subsequently diagnosed with ASD from children with TD and OPD. Its high sensitivity and specificity, coupled with its efficiency in terms of time and cost, suggest this broadband tool should be tested in a pilot screening survey of toddlers in the general population.     

Autism spectrum disorders in children and adolescents with Moebius sequence

Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups. The primary caregivers of all children and adolescents with Moebius sequence aged 6–17 years known to the German Moebius foundation were anonymously asked to complete two screening measures of ASD [Behavior and Communication Questionnaire (VSK); Marburger Asperger’s Syndrome Rating Scale (MBAS)]. For those who reached the cut-off for ASD, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, WISC-III, and Kinder-DIPS) should be administered. Minimal diagnostic criteria for Moebius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Familiar cases should be excluded. The primary caregivers of 35/46 children and adolescents (18 males, 17 females, mean age 11.5 years) sent back completed questionnaires, but only 27 subjects met inclusion criteria. According to the primary caregivers, none of these subjects showed mental retardation. Two probands (both males 9 and 16 years old) reached the cut-off of the MBAS whereas the results of the VSK did not indicate ASDs in any of the patients. The 9 year old boy could be examined personally and did not meet diagnostic criteria of ASD. ASDs might be not as frequent as reported in previous studies on patients with Moebius sequence, at least not in patients without mental retardation.     

Face memory and object recognition in children with high-functioning autism or Asperger syndrome and in their parents

Children with Autism Spectrum Disorders (ASDs) have reported to have impairments in face, recognition and face memory, but intact object recognition and object memory. Potential abnormalities, in these fields at the family level of high-functioning children with ASD remains understudied despite, the ever-mounting evidence that ASDs are genetic and highly heritable disorders. Recent studies indicate also that face perception is heritability ability, thus impairments in facial memory may be, inherited from parents with or without ASD symptoms. We studied 45 high-functioning children with, ASD (M = 11.5 years) and 26 of their parents as well as 70 control community children (M = 12.4 years), and 73 of their parents. Three subtests of the Developmental Neuropsychological Evaluation (NEPSY), were administered. Results indicate that younger children with ASD (<11.9 years old) had poorer, facial memory than their control counterparts and that the facial memory improves with age in, children with ASD. Adolescents with ASD (>11.9 years) performed better than their community, counterparts in visual object recognition. Parents of children with ASD share weakness in facial, memory ability and strength in visual object recognition with their children. Thus, families with, HFA/AS may benefit interventions of social cognition and attentional strategy.