Autism Research and Treatment最新文献

Although the DSM-5 has recently created a single category of autism spectrum disorder (ASD), delineation of its putative subtypes remains clinically useful. For this process, screening instruments should ideally be brief, simple, and easily available. The aim of this study is to describe the validity of one such instrument. We administered the Michigan Autism Spectrum Questionnaire (MASQ), a 10-item questionnaire, to 42 patients with ASD (age range 6-13 years, mean 9.7 years, SD 2.5, one female) and 18 patients with other psychiatric disorders (age range 6-17 years, mean 11.7 years, SD 3.8, 6 females). Responses to each item were scored from 0 to 4 yielding a total score of 30. Patients with intellectual disability were excluded. As a group, patients with ASD scored higher than those with other psychiatric disorders (Chi-square test with 1 df = 16.019, P < 0.0001). Within the ASD group, a linear discriminant analysis found that the best cut-off points were 22 or above for Asperger syndrome, 14 to 21 for autism/PDDNOS, and less than 14 for those with other psychiatric disorders. We propose that the MASQ can be used as a brief measure to screen high-functioning ASD from other psychiatric disorders and to identify its possible subtypes.

This study examined (1) the prevalence of psychotropic medication use for a sample of children with high-functioning autism spectrum disorders (HFASDs), (2) the extent to which psychotropic agents were linked to targeted symptoms, and (3) predictors of psychotropic use. A total of 115 children, ages 6-13, with HFASDs who were enrolled in psychosocial treatment trials were included in this study. Parents completed extensive background and rating forms prior to treatment that included data on demographic characteristics, child health, child medication use, and child ASD-related symptoms. Results indicated that 33% (n = 38) of the sample was taking psychotropic medication with the most common being stimulants (25%; n = 29), antidepressants (10%; n = 12), and neuroleptics (6%; n = 7). All children taking stimulants had target symptoms that were appropriate for stimulant medication, whereas 57% of those taking neuroleptics and 42% of those taking antidepressants did not have targeted symptoms consistent with the medication. Logistic regression for the major psychotropic drug categories indicated that lower IQ was a significant predictor of increased antidepressant and neuroleptic use. A higher level of ASD-related symptoms was related to the likelihood of stimulant use.

Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.

Abnormalities in folate-dependent one-carbon metabolism have been reported in many children with autism. Because inadequate choline and betaine can negatively affect folate metabolism and in turn downstream methylation and antioxidant capacity, we sought to determine whether dietary intake of choline and betaine in children with autism was adequate to meet nutritional needs based on national recommendations. Three-day food records were analyzed for 288 children with autism (ASDs) who participated in the national Autism Intervention Research Network for Physical Health (AIR-P) Study on Diet and Nutrition in children with autism. Plasma concentrations of choline and betaine were measured in a subgroup of 35 children with ASDs and 32 age-matched control children. The results indicated that 60-93% of children with ASDs were consuming less than the recommended Adequate Intake (AI) for choline. Strong positive correlations were found between dietary intake and plasma concentrations of choline and betaine in autistic children as well as lower plasma concentrations compared to the control group. We conclude that choline and betaine intake is inadequate in a significant subgroup of children with ASDs and is reflected in lower plasma levels. Inadequate intake of choline and betaine may contribute to the metabolic abnormalities observed in many children with autism and warrants attention in nutritional counseling.

Eye-tracking studies on exploration of faces and objects in autism provided important knowledge but only in a constraint condition (chin rest, total time looking at screen not reported), without studying potential differences between subjects with autism spectrum disorder (ASD) and controls in spontaneous visual attention toward a screen presenting these stimuli. This study used eye tracking to compare spontaneous visual attention to a screen displaying a face or an object between children with autism and controls in a nonconstraint condition and to investigate the relationship with clinical characteristics in autism group. Time exploring screen was measured during passive viewing of static images of faces or objects. Autistic behaviors were assessed by the CARS and the BSE-R in autism group. In autism group, time exploring face screen and time exploring object screen were lower than in controls and were not correlated with degree of distractibility. There was no interaction between group and type of image on time spent exploring screen. Only time exploring face screen was correlated with autism severity and gaze impairment. Results highlight particularities of spontaneous visual attention toward a screen displaying faces or objects in autism, which should be taken into account in future eye-tracking studies on face exploration.

Recent studies suggest that many children with milder autism spectrum disorder (ASD) are undiagnosed, untreated, and being educated in mainstream classes without support and that school teachers might be the best persons to identify a child's social deviance. At present, only a few screening measures using teacher ratings of ASD have been validated. The aim of this study was to examine the utility of teacher ratings on the Social Responsiveness Scale (SRS), a quantitative measure of ASD. We recruited 130 participants aged 4 to 17 years from local schools or local pediatric outpatient clinics specializing in neurodevelopmental disorders that included 70 children with ASD. We found that the teacher-report SRS can be reliably and validly applied to children as a screening tool or for other research purposes, and it also has cross-cultural comparability. Although parent-teacher agreement was satisfactory overall, a discrepancy existed for children with ASD, especially for girls with ASD. To improve sensitivity in children at higher risk, especially girls, we cannot overstate the importance of using standardized norms specific to gender, informant, and culture.

Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology.

Adaptive behavior rating scales are frequently used to gather information on the adaptive functioning of children with high-functioning autism spectrum disorders (HFASDs), yet little is known about the extent to which these measures yield comparable results. This study was conducted to (a) document the parent-rated VABS-II, BASC-2, and ABAS-II adaptive behavior profiles of 6- to 11-year-olds with HFASDs (including relative strengths and weaknesses); (b) examine the extent to which these measures yielded similar scores on comparable scales; and (c) assess potential discrepancies between cognitive ability and adaptive behavior across the measures. All three adaptive measures revealed significant deficits overall for the sample, with the VABS-II and ABAS-II indicating relative weaknesses in social skills and strengths in academic-related skills. Cross-measure comparisons indicated significant differences in the absolute magnitude of scores. In general, the VABS-II yielded significantly higher scores than the BASC-2 and ABAS-II. However, the VABS-II and ABAS-II yielded scores that did not significantly differ for adaptive social skills which is a critical area to assess for children with HFASDs. Results also indicated significant discrepancies between the children's average IQ score and their scores on the adaptive domains and composites of the three adaptive measures.

The modulation of the redox microenvironment is an important regulator of immune cell activation and proliferation. To investigate immune cell redox status in autism we quantified the intracellular glutathione redox couple (GSH/GSSG) in resting peripheral blood mononuclear cells (PBMCs), activated monocytes and CD4 T cells and the extracellular cysteine/cystine redox couple in the plasma from 43 children with autism and 41 age-matched control children. Resting PBMCs and activated monocytes from children with autism exhibited significantly higher oxidized glutathione (GSSG) and percent oxidized glutathione equivalents and decreased glutathione redox status (GSH/GSSG). In activated CD4 T cells from children with autism, the percent oxidized glutathione equivalents were similarly increased, and GSH and GSH/GSSG were decreased. In the plasma, both glutathione and cysteine redox ratios were decreased in autistic compared to control children. Consistent with decreased intracellular and extracellular redox status, generation of free radicals was significantly elevated in lymphocytes from the autistic children. These data indicate primary immune cells from autistic children have a more oxidized intracellular and extracellular microenvironment and a deficit in glutathione-mediated redox/antioxidant capacity compared to control children. These results suggest that the loss of glutathione redox homeostasis and chronic oxidative stress may contribute to immune dysregulation in autism.

Autism affects 1 : 88 children in the United States. Familial history of autoimmune disease, autoantibodies in the serum of mothers when there is more than one autistic offspring, and neuroglial response in CSF and brain tissue in autistic patients suggest an immunological variable may be associated with this condition. Lenalidomide has the potential to invoke changes in TNF-α with less toxicity than thalidomide. This pilot study evaluated lenalidomide at reduction of TNF-α and improvement of behavior and language in children with autism with elevated TNF-α. Subjects with elevated TNF-α were given 2.5 mgs lenalidomide daily for 12-weeks. Pharmacodynamics and safety was evaluated. Changes in language and autistic behaviors after six and twelve weeks were measured. Although statistical significance was not achieved for most measures, there were trends toward improvement. After 6-weeks, mean receptive language increased: 60.67 ± 12.06 to 65.00 ± 15.10 (P = 0.11) and symptoms of autism decreased (40.75 ± 5.96 versus 38.67 ± 7.90, P = 0.068). After 12-weeks, CSF-TNF-α declined 57% ± 25% from 80.5 ± 41.03 to 38.0 ± 31.27 (P = 0.068). Serum TNF-α declined 57% (92.50 ± 68.92 to 40.25 ± 44.53 (P = 0.048). This study suggests that lenalidomide is tolerated as a treatment by children with autism and should be further studied as a potential agent for cytockine inflammation.