1. {{Correction for Schumann et al., Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption}}. {Proc Natl Acad Sci U S A};2011 (May 13)
2. Ashwood P, Corbett BA, Kantor A, Schulman H, Van de Water J, Amaral DG. {{In search of cellular immunophenotypes in the blood of children with autism}}. {PLoS One};2011;6(5):e19299.
BACKGROUND: Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism. METHODS: We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (n = 70) compared with age-matched controls (n = 35). Children with a confirmed diagnosis of autism (4-6 years of age) were further subdivided into low (IQ<68, n = 35) or high functioning (IQ>/=68, n = 35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry. RESULTS: There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls. CONCLUSIONS: These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed.
3. Boyd BA, McDonough SG, Bodfish JW. {{Evidence-Based Behavioral Interventions for Repetitive Behaviors in Autism}}. {J Autism Dev Disord};2011 (May 17)
Restricted and repetitive behaviors (RRBs) are a core symptom of autism spectrum disorders (ASD). There has been an increased research emphasis on repetitive behaviors; however, this research primarily has focused on phenomenology and mechanisms. Thus, the knowledge base on interventions is lagging behind other areas of research. The literature suggests there are evidence-based practices to treat « lower order » RRBs in ASD (e.g., stereotypies); yet, there is a lack of a focused program of intervention research for « higher order » behaviors (e.g., insistence on sameness). This paper will (a) discuss barriers to intervention development for RRBs; (b) review evidence-based interventions to treat RRBs in ASD, with a focus on higher order behaviors; and (c) conclude with recommendations for practice and research.
4. Hess CR, Landa RJ. {{Predictive and Concurrent Validity of Parent Concern About Young Children at Risk for Autism}}. {J Autism Dev Disord};2011 (May 17)
Parents’ concerns about their children’s development were examined prospectively at 14, 24, and 36 months for 89 younger siblings of a child with autism. Parent reported concern was high at all ages (40-75%) and was higher at 24 and 36 months in children with ASD than non-ASD outcomes (p < .05). Communication concerns were reported most frequently. Parent concern compared to impairment classification based on concurrent standardized tests provided better specificity than sensitivity, and was better for communication than social functioning. Parent communication concern (but not social concern) at 24 months and 36 months predicted ASD versus non-ASD outcome; however, children’s impairment on standardized tests yielded greater predictive value at all ages (p < .001). Close monitoring of this at risk group is warranted.
5. Hollway JA, Aman MG. {{Sleep correlates of pervasive developmental disorders: A review of the literature}}. {Res Dev Disabil};2011 (May 12)
Sleep disturbance is a significant problem in the general pediatric population, and it occurs even more frequently in children with pervasive developmental disorders (PDDs). Much time and energy have been spent examining the characteristics that predispose children to insomnia and it is likely that equivalent factors influence sleep in PDDs. Though similarly affected, it is the unique set of characteristics incumbent in a diagnosis of PDD that has additive effects and increases the likelihood for developing other predisposing factors and subsequent sleep loss. This review summarized research that has explored the behavioral, cognitive, and emotional correlates of sleep disturbance in children with PDDs. The literature provided 38 sleep studies that used either subjective or objective sleep measures. Of these, 17 met criteria for inclusion. Studies were evaluated for their attempts at matching their study samples and adjusting for possible confounding variables. The results revealed that the combined effects of autism symptom severity, internalizing behavior, and externalizing behavior, were the main predisposing factors for the development of insomnia. Other factors included medical conditions, epilepsy, and medication use (likely a proxy for behavior difficulty and even sleep disorder). A bidirectional theoretical framework for sleep disturbance in children with PDDs has been posited as a conceptual guide for future study. Recommendations for future study designs are included.
6. Kovshoff H, Hastings RP, Remington B. {{Two-Year Outcomes for Children With Autism After the Cessation of Early Intensive Behavioral Intervention}}. {Behav Modif};2011 (May 17)
Evidence from recent meta-analytic and narrative review suggests that early intensive behavioral intervention (EIBI) may improve life chances of preschool children with autism. Unfortunately, there are few data indicating whether early gains are maintained after intervention ceases. The purpose of the present study was to establish the 2-year follow-up outcome for children with autism (N = 41) who had participated in an earlier 2-year controlled comparison of EIBI. Twenty-three children in the intervention group (100% of original sample) and 18 in the treatment-as-usual comparison group (86% of original sample) were located and retested. Group differences favoring intervention substantially diluted in this period but varied significantly between subgroups who had received university-supervised and parent-commissioned interventions, favoring the latter. These groups differed in terms of their baseline characteristics and intensity ofintervention. Results strongly suggesta need for better characterization of those children who would benefit from more active maintenance programs.
7. M DEJ, Punt M, E DEG, Minderaa RB, Hadders-Algra M. {{Minor neurological dysfunction in children with autism spectrum disorder}}. {Dev Med Child Neurol};2011 (May 13)
Aim The aim of this study was to improve the understanding of brain function in children with autism spectrum disorder (ASD) in relation to minor neurological dysfunctions (MNDs). Method We studied MNDs in 122 children (93 males, 29 females; mean age 8y 1mo, SD 2y 6mo) who, among a total cohort of 705 children (513 males, 192 females; mean age 9y, SD 2y 0.5mo) referred to a regional outpatient non-academic psychiatric centre in the Netherlands, were diagnosed with ASD after an extensive multidisciplinary psychiatric assessment. Children with clear neurological abnormalities (e.g. cerebral palsy or spina bifida) were excluded from the study. MNDs were assessed in all 705 children using the Touwen examination method. Special attention was paid to the severity and type of MND. Data of the children with ASD were compared with neurological morbidity data of children with other psychiatric disorders and with children in the general population, who were born at Groningen University Hospital between 1975 and 1978. Results Seventy-four percent of the children with ASD showed complex MNDs compared with 52% of the children with other psychiatric disorders and 6% of the reference group (chi(2) =18.0, p<0.001; chi(2) =937.5, p<0.001 respectively). Specific dysfunctions frequently encountered in ASD were dysfunctional posture and muscle tone, fine manipulative disability, dyscoordination, and excessive associated movements. Conclusion These findings suggest a contribution of dysfunctional supraspinal networks involving multiple parts of the brain in the pathogenesis of ASD. This is consistent with findings from neuroimaging studies, and highlights the importance of neurological examinations in paediatric psychiatric assessments.
8. Mahdhaoui A, Chetouani M, Cassel RS, Saint-Georges C, Parlato E, Laznik MC, Apicella F, Muratori F, Maestro S, Cohen D. {{Computerized home video detection for motherese may help to study impaired interaction between infants who become autistic and their parents}}. {Int J Methods Psychiatr Res};2011 (Mar);20(1):e6-e18.
Autism is a well-defined clinical syndrome after the second year of life, but information on autism in the first two years of life is still lacking. The study of home videos has described children with autism during the first year of life as not displaying the rigid pattern typical of later symptoms. Therefore, developmental/environmental factors are claimed in addition to genetic/biological ones to explain the onset of autism during maturation. Here we describe (1) a developmental hypothesis focusing on the possible implication of motherese impoverishment during the course of parent-infant interactions as a possible co-factor; (2) the methodological approach we used to develop a computerized algorithm to detect motherese in home videos; (3) the best configuration performance of the detector in extracting motherese from home video sequences (accuracy = 82% on speaker-independent versus 87.5% on speaker-dependent) that we should use to test this hypothesis. Copyright (c) 2011 John Wiley & Sons, Ltd.
9. Ming X, Hashim A, Fleishman S, West T, Kang N, Chen X, Zimmerman-Bier B. {{Access to specialty care in autism spectrum disorders-a pilot study of referral source}}. {BMC Health Serv Res};2011 (May 14);11(1):99.
ABSTRACT: BACKGROUND: In the United States, a medical home model has been shown to improve the outcomes for children with special health care needs. As part of this model, primary care physicians provide comprehensive medical care that includes identification of delayed and/or atypical development in children and coordination of care with specialists. However, it is not clear if families of children with ASD rely on the medical home model for care of their child to the same extent as families of children with other special health care needs. This study aims to add to the understanding of medical care for children with ASD by examining the referral source for specialty care. METHOD: This retrospective study was accomplished by comparing who initiated the specialist evaluation (source) at intake for children with ASD compared to those with other neurological disorders. All children were evaluated at a major medical center in Northern New Jersey. To account for referral bias, a comparison was made also between who initiated the specialty evaluation to the pediatric neurologist vs those to other specialists of a multispecialty ASD practice. The source that prompted a specialty referral as well as the reason for the specialty referral of 189 ASD children and 108 non-ASD neurological disordered children were analyzed. RESULTS: The specialty evaluations of ASD were predominantly parent initiated. There were significantly less referrals received from primary care physicians for children with ASD than those for other neurodevelopmental disorders. This pattern of non-physician generated referral was similar amongst all specialty groups. Requirement of an insurance referral was not associated with a physician prompted specialty visit., We identified different patterns of referral to our specialty clinics for children with ASD vs. children with other neurolodevelopmental disorders. CONCLUSION: The majority of the families of children with ASD evaluated at our autism center did not indicate that a primary care physician initiated the specialty referral. This study suggests that families of children with ASD interface differently with the primary care provider than families of children with other neurological disorders.
10. Mouridsen SE, Rich B, Isager T. {{Fractures in Individuals With and Without a History of Infantile Autism. A Danish Register Study Based on Hospital Discharge Diagnoses}}. {J Autism Dev Disord};2011 (May 17)
We compared the prevalence and types of fractures in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with 336 matched controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time was 30.3 years (range 27.3-30.4 years), and mean age at follow-up was 42.7 years (range 27.3-57.3 years). Of the 118 individuals with IA, 14 (11.9%) were registered with at least one fracture diagnosis against 83 (24.7%) in the comparison group (p = 0.004; OR = 0.41; 95%CI 0.22-0.76), but the nature of their fractures seems somewhat different. Epilepsy was a risk factor, but only in the comparison group. Our results lend no support to the notion that fracture is a common comorbid condition in a population of people diagnosed with IA as children.
11. Naidu S, Johnston MV. {{Neurodevelopmental disorders: Clinical criteria for Rett syndrome}}. {Nat Rev Neurol};2011 (May 17)
12. Naik US, Gangadharan C, Abbagani K, Nagalla B, Dasari N, Manna SK. {{A study of nuclear transcription factor-kappa B in childhood autism}}. {PLoS One};2011;6(5):e19488.
BACKGROUND: Several children with autism show regression in language and social development while maintaining normal motor milestones. A clear period of normal development followed by regression and subsequent improvement with treatment, suggests a multifactorial etiology. The role of inflammation in autism is now a major area of study. Viral and bacterial infections, hypoxia, or medication could affect both foetus and infant. These stressors could upregulate transcription factors like nuclear factor kappa B (NF-kappaB), a master switch for many genes including some implicated in autism like tumor necrosis factor (TNF). On this hypothesis, it was proposed to determine NF-kappaB in children with autism. METHODS: Peripheral blood samples of 67 children with autism and 29 control children were evaluated for NF-kappaB using electrophoretic mobility shift assay (EMSA). A phosphor imaging technique was used to quantify values. The fold increase over the control sample was calculated and statistical analysis was carried out using SPSS 15. RESULTS: We have noted significant increase in NF-kappaB DNA binding activity in peripheral blood samples of children with autism. When the fold increase of NF-kappaB in cases (n = 67) was compared with that of controls (n = 29), there was a significant difference (3.14 vs. 1.40, respectively; p<0.02). CONCLUSION: This finding has immense value in understanding many of the known biochemical changes reported in autism. As NF-kappaB is a response to stressors of several kinds and a master switch for many genes, autism may then arise at least in part from an NF-kappaB pathway gone awry.
13. O’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE. {{Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations}}. {Nat Genet};2011 (May 15)
Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs.
14. Ozsivadjian A, Knott F. {{Anxiety problems in young people with autism spectrum disorder: A case series}}. {Clin Child Psychol Psychiatry};2011 (Apr);16(2):203-214.
It is now well established that the prevalence of mental health difficulties in individuals with autism spectrum disorders (ASD) is considerably higher than in the general population. With recent estimates of the prevalence of autism spectrum disorders being as high as one percent, increasing numbers of children and young people are presenting to local and specialist services with mental health problems in addition to a diagnosis of ASD. Many families report that the impact of the mental health problems can be as or more impairing than the autism spectrum difficulties themselves. Clinical services are frequently called upon to treat these difficulties; however, there is limited evidence for the effectiveness of treatments in this population. This paper reports a case series of children and adolescents with ASD and an anxiety disorder who were treated with a standard cognitive behaviour therapy (CBT) rationale adapted to take account of the neuropsychological features of ASD. Common features of the presentation of the disorders and also treatment processes are discussed.
15. Pardini M, Elia M, Garaci FG, Guida S, Coniglione F, Krueger F, Benassi F, Emberti Gialloreti L. {{Long-term Cognitive and Behavioral Therapies, Combined with Augmentative Communication, are Related to Uncinate Fasciculus Integrity in Autism}}. {J Autism Dev Disord};2011 (May 14)
Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate fasciculus structural properties correlated significantly with therapy length and early onset, as well as to clinical outcome, independently from IQ, age or symptoms severity at therapy onset. Moreover, adherence to therapy was linked with better clinical outcome and uncinate fasciculus structural integrity. The results point to the capability of a long-term rehabilitation of subjects with low-functioning autism to produce white-matter structural modifications, which could thus play a role in the rehabilitative outcome.
16. Paul R, Loomis R, Chawarska K. {{Adaptive Behavior in Toddlers Under Two with Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (May 15)
The Vineland Adaptive Behavior Scale was administered to 54 children diagnosed with autism spectrum disorder (ASD) before age 2, and a matching group of 18 toddlers with developmental delay (DD). The group with ASD was more impaired on all scales of the Vineland than DD peers. When 18 ASD/DD pairs very closely matched on age, verbal and nonverbal development were selected, differences were found only on Vineland Receptive Communication and Daily Living. Correlation analyses to explore connection of these areas of difference with cognition and autistic symptoms suggested that Vineland Daily Living scores were significantly correlated with nonverbal ability and with ADOS total algorithm scores. Vineland Receptive Communication scores correlated significantly only with ADOS total algorithms. The clinical implications of these findings are discussed.
17. Soke GN, Philofsky A, Diguiseppi C, Lezotte D, Rogers S, Hepburn S. {{Longitudinal changes in Scores on the Autism Diagnostic Interview-Revised (ADI-R) in pre-school children with autism: Implications for diagnostic classification and symptom stability}}. {Autism};2011 (May 17)
We prospectively examined mean changes in Autism Diagnostic Interview-Revised (ADI-R) Total and Domains scores and stability of the ADI-R diagnostic classification in 28 children with autism initially assessed at age 2-4 years and reassessed 2 years later. Mean Total, Social Interaction, and Communication scores decreased significantly from Time 1 to Time 2 Restricted/repetitive Domain mean scores did not change over time. The ADI-R diagnostic classification was stable in 67% of children using the current published criteria. The stability increased to 78% when a modified criterion was used in the Restricted/repetitive Domain and to 88% when the broader ASD criteria were used. Among pre-schoolers with autism, parent-reported symptoms decreased significantly at two-year follow-up in Social and Communication Domains but not in the Restricted/repetitive Domain. However, ADI-R diagnostic classification remained relatively stable over time. Revising ADI-R diagnostic criteria in the Restricted/repetitive Domain or including the broader ASD criteria may improve its sensitivity and diagnostic stability in younger children.
18. Yu J, He X, Yao D, Li Z, Li H, Zhao Z. {{A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort}}. {Behav Brain Funct};2011 (May 14);7(1):13.
ABSTRACT: BACKGROUND: Synaptic genes, NLGN3 and NLGN4X, two homologous members of the neuroligin family, have been supposed as predisposition loci for autism spectrum disorders (ASDs), and defects of these two genes have been identified in a small fraction of individuals with ASDs. But no such rare variant in these two genes has as yet been adequately replicated in Chinese population and no common variant has been further investigated to be associated with ASDs. METHODS: 7 known ASDs-related rare variants in NLGN3 and NLGN4X genes were screened for replication of the initial findings and 12 intronic tagging single nucleotide polymorphisms (SNPs) were genotyped for case-control association analysis in a total of 229 ASDs cases and 184 control individuals in a Chinese Han cohort, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS: We found that a common intronic variant, SNP rs4844285 in NLGN3 gene, and a specific 3-marker haplotype XA-XG-XT (rs11795613-rs4844285-rs4844286) containing this individual SNP were associated with ASDs and showed a male bias, even after correction for multiple testing (SNP allele: P=0.048, haplotype:P=0.032). Simultaneously, none of these 7 known rare mutations of NLGN3 and NLGN4X gene was identified either in our patients with ASDs or controls, giving further evidence that these known rare variants might be not enriched in Chinese Han cohort. CONCLUSION: The present study provides initial evidence that a common variant in NLGN3 gene may play a role in the etiology of ASDs among affected males in Chinese Han population, and further supports the hypothesis that defect of synapse might involvement in the pathophysiology of ASDs.
19. Zheng F, Wang L, Jia M, Yue W, Ruan Y, Lu T, Liu J, Li J, Zhang D. {{Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study}}. {Behav Brain Funct};2011 (May 15);7(1):14.
ABSTRACT: BACKGROUND: Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. METHODS: We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software. RESULTS: We found three SNPs showed significant associations with autism (rs4366301: G>C, Z=2.872, p=0.004; rs11585959: T>C, Z=2.199, p=0.028; rs6668845: A>G, Z=2.326, p=0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still signicant after using the permutation method to obtain empirical p values. CONCLUSIONS: Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.
