Adaptive Functioning in Autism Spectrum Disorder During the Transition to Adulthood.

There is a dearth of research regarding adaptive functioning during the transition to adulthood in autism spectrum disorder (ASD). Profiles on the Vineland Adaptive Behavior Scales, Second Edition were examined by age and intellectual ability in 75 participants with ASD (16-58 years). Results extend previous reports of a cognitive advantage over adaptive functioning in children by demonstrating a similar pattern in an older sample. Daily living skills were a relative strength compared to communication and socialization in adults, but not adolescents. In general, highest subdomain scores were observed in writing skills and lowest scores were observed in interpersonal skills. Regardless of cognitive ability, all standard scores were well below average, indicating a need for lifelong intervention that targets adaptive functioning.

Revisiting cognitive and adaptive functioning in children and adolescents with autism spectrum disorder.

Profiles of performance on the Stanford Binet Intelligence Scales (SB5) and Vineland Adaptive Behavior Scales (VABS) were examined in 73 children and adolescents with autism spectrum disorder. SB5 cognitive profiles were observed to be similar between participants with and without early language delay, but different between participants with and without intellectual disability. With few exceptions, the distribution and cognitive profiles of participants with specific nonverbal IQ-verbal IQ and abbreviated IQ-full scale IQ discrepancy patterns paralleled previous reports. A cognitive functioning advantage over adaptive functioning was observed to be strongest in participants without intellectual disability and older participants. The previously reported VABS "autism profile" was not observed. Current findings clarify previous research and will inform the diagnostic process and treatment planning.

Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder.

OBJECTIVE: Converging lines of evidence point to the existence of immune dysfunction in autism spectrum disorder (ASD), which could directly affect several key neurodevelopmental processes. Previous studies have shown higher cytokine levels in patients with autism compared with matched controls or subjects with other developmental disorders. In the current study, we used plasma-cytokine profiling for 25 discordant sibling pairs to evaluate whether these alterations occur within families with ASD. METHODS: Plasma-cytokine profiling was conducted using an array-based multiplex sandwich ELISA for simultaneous quantitative measurement of 40 unique targets. We also analyzed the correlations between cytokine levels and clinically relevant quantitative traits (Vineland Adaptive Behavior Scale in Autism (VABS) composite score, Social Responsiveness Scale (SRS) total T score, head circumference, and full intelligence quotient (IQ)). In addition, because of the high phenotypic heterogeneity of ASD, we defined four subgroups of subjects (those who were non-verbal, those with gastrointestinal issues, those with regressive autism, and those with a history of allergies), which encompass common and/or recurrent endophenotypes in ASD, and tested the cytokine levels in each group. RESULTS: None of the measured parameters showed significant differences between children with ASD and their related typically developing siblings. However, specific target levels did correlate with quantitative clinical traits, and these were significantly different when the ASD subgroups were analyzed. It is notable that these differences seem to be attributable to a predisposing immunogenetic background, as no other significant differences were noticed between discordant sibling pairs. Interleukin-1ß appears to be the cytokine most involved in quantitative traits and clinical subgroups of ASD. CONCLUSIONS: In the present study, we found a lack of significant differences in plasma-cytokine levels between children with ASD and in their related non-autistic siblings. Thus, our results support the evidence that the immune profiles of children with autism do not differ from their typically developing siblings. However, the significant association of cytokine levels with the quantitative traits and the clinical subgroups analyzed suggests that altered immune responses may affect core feature of ASD.

Emotion regulation in the context of frustration in children with high functioning autism and their typical peers.

BACKGROUND: It is well accepted that emotion regulation difficulties are a serious concern for children with ASD, yet empirical studies of this construct are limited for this population. The present study describes group differences between high functioning children with autism and their typical peers in frustration and discrete coping strategies for emotion regulation. We also use sequential analyses to test differences in the efficacy of individual coping strategies at regulating children's frustration. METHODS: Subjects were 20 children with autism (M = 59 months) and 20 developmentally matched typically developing children (M = 50 months). Measures of children's frustration (negative facial expressions and behaviors, negative vocalizations, resignation) and emotion regulation coping strategies were observationally coded from structured video recordings. RESULTS: Children with autism displayed a higher intensity and duration of resignation, and the group difference became most pronounced when children worked alone during the parent-absent segment of the locked box task. Children with autism used significantly more avoidance and venting strategies, and fewer constructive strategies than typical children. Sequential analyses revealed that social support strategies (orienting and verbalizing to the experimenter) were ineffective for children with autism, while these behaviors, vocal venting, and distraction strategies were all effective for typically developing children. CONCLUSIONS: The results go beyond the recent literature by offering a rich description of children's efforts to regulate their frustration when faced with challenge, and point to important contextual differences in the efficacy of children's coping strategies.

Autism and increased paternal age related changes in global levels of gene expression regulation.

A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL) of children with autism (n = 82) and controls (n = 64). Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.

Decreased serum arylesterase activity in autism spectrum disorders.

The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65×10⁻¹6). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P=2.84×10⁻¹6). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels.