1. Atladottir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET. {{Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders}}. {Pediatrics};2009 (Jul 5)
Objectives: Recent studies suggest that familial autoimmunity plays a part in the pathogenesis of ASDs. In this study we investigated the association between family history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform confirmatory analyses based on results from previous studies, as well as various explorative analyses. Methods: The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689196 children). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression. Results: A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased risk of infantile autism was observed for children with a family history of type 1 diabetes. Conclusions: Associations regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous studies. A significant association between maternal history of celiac disease and ASDs was observed for the first time. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.
2. Cheng L, Ge Q, Xiao P, Sun B, Ke X, Bai Y, Lu Z. {{Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray}}. {Int J Mol Sci};2009 (Jun);10(6):2487-2500.
Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (chi(2) = 7.809, p = 0.005) and genotype (chi(2) = 7.800, p = 0.020). In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (chi(2) = 28.19, p = 3.44e-005). We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.
3. Gadow KD, Roohi J, Devincent CJ, Kirsch S, Hatchwell E. {{Association of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety, ADHD and Tics in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2009 (Jul 7)
The aim of the study is to examine rs4680 (COMT) and rs6265 (BDNF) as genetic markers of anxiety, ADHD, and tics. Parents and teachers completed a DSM-IV-referenced rating scale for a total sample of 67 children with autism spectrum disorder (ASD). Both COMT (p = 0.06) and BDNF (p = 0.07) genotypes were marginally significant for teacher ratings of social phobia (etap (2) = 0.06). Analyses also indicated associations of BDNF genotype with parent-rated ADHD (p = 0.01, etap (2) = 0.10) and teacher-rated tics (p = 0.04; etap (2) = 0.07). There was also evidence of a possible interaction (p = 0.02, etap (2) = 0.09) of BDNF genotype with DAT1 3′ VNTR with tic severity. BDNF and COMT may be biomarkers for phenotypic variation in ASD, but these preliminary findings remain tentative pending replication with larger, independent samples.
4. Hartley SL, Sikora DM. {{Sex Differences in Autism Spectrum Disorder: An Examination of Developmental Functioning, Autistic Symptoms, and Coexisting Behavior Problems in Toddlers}}.{ J Autism Dev Disord};2009 (Jul 7)
Little is known about the female presentation of autism spectrum disorder (ASD) during early childhood. We investigated sex differences in developmental profiles using the Mullen Scales of Early Learning, autistic symptoms on the ADOS-G, and coexisting behavior problems on the CBCL in 157 boys and 42 girls with ASD aged 1.5-3.9 years. Overall, boys and girls evidenced a markedly similar pattern of developmental profiles, autism symptoms, and coexisting behavior problems, although subtle differences exist. Boys and girls evidenced a similar pattern of developmental strengths and weaknesses. Girls with ASD evidenced greater communication deficits than boys and boys evidenced more restricted, repetitive, and stereotyped behavior than girls. Girls exhibited more sleep problems and anxious or depressed affect than boys.
5. Minio-Paluello I, Lombardo MV, Chakrabarti B, Wheelwright S, Baron-Cohen S. {{Response to Smith’s Letter to the Editor ‘Emotional Empathy in Autism Spectrum Conditions: Weak, Intact, or Heightened?’}} {J Autism Dev Disord};2009 (Jul 8)
6. Poot M, Beyer V, Schwaab I, Damatova N, Van’t Slot R, Prothero J, Holder SE, Haaf T. {{Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder}}. {Neurogenetics};2009 (Jul 7)
Patients with autism spectrum disorder (ASD) frequently harbour chromosome rearrangements and segmental aneuploidies, which allow us to identify candidate genes. In a boy with mild facial dysmorphisms, speech delay and ASD, we reconstructed by karyotyping, FISH and SNP array-based segmental aneuploidy profiling a highly complex chromosomal rearrangement involving at least three breaks in chromosome 1 and seven breaks in chromosome 7. Chromosome banding revealed an inversion of region 7q32.1-7q35 on the derivative chromosome 7. FISH with region-specific BACs mapped both inversion breakpoints and revealed additional breaks and structural changes in the CNTNAP2 gene. Two gene segments were transposed and inserted into the 1q31.2 region, while the CNTNAP2 segment between the two transposed parts as well as intron 13 to the 5-UTR were retained on the der(7). SNP array analysis revealed an additional de novo deletion encompassing the distal part of intron1 and exon 2 of CNTNAP2, which contains FOXP2 binding sites. Second, we found another de novo deletion on chromosome 1q41, containing 15 annotated genes, including KCTD3 and USH2A. Disruptions of the CNTNAP2 gene have been associated with ASD and with Gilles de la Tourette syndrome (GTS). Comparison of disruptions of CNTNAP2 in patients with GTS and ASD suggests that large proximal disruptions result in either GTS or ASD, while relatively small distal disruptions may be phenotypically neutral. For full-blown ASD to develop, a proximal disruption of CNTNAP2 may have to occur concomitantly with additional genome mutations such as hemizygous deletions of the KCTD3 and USH2A genes.
7. Rogers SJ. {{What are infant siblings teaching us about autism in infancy?}} {Autism Res};2009 (Jul 6)
International research to understand infant patterns of development in autism spectrum disorders (ASDs) has recently focused on a research paradigm involving prospective longitudinal studies of infant siblings of children with autism. Such designs use a comparison group of infant siblings without any familial risks (the low-risk group) to gather longitudinal information about developmental skills across the first 3 years of life, followed by clinical diagnosis of ASD at 36 months. This review focuses on five topics: presence of ASD in the infant sibling groups, patterns and characteristics of motor development, patterns and characteristics of social and emotional development, patterns and characteristics of intentional communication, both verbal and nonverbal, and patterns that mark the onset of behaviors pathognomonic for ASD. Symptoms in all these areas typically begin to be detected during the age period of 12-24 months in infants who will develop autism. Onset of the symptoms occurs at varying ages and in varying patterns, but the pattern of frank loss of skills and marked regression reported from previous retrospective studies in 20-30% of children is seldom reported in these infant sibling prospective studies. Two surprises involve the very early onset of repetitive and unusual sensory behaviors, and the lack of predictive symptoms at the age of 6 months. Contrary to current views that autism is a disorder that profoundly affects social development from the earliest months of life, the data from these studies presents a picture of autism as a disorder involving symptoms across multiple domains with a gradual onset that changes both ongoing developmental rate and established behavioral patterns across the first 2-3 years of life.
8. Towgood KJ, Meuwese JD, Gilbert SJ, Turner MS, Burgess PW. {{Advantages of the Multiple Case Series Approach to the Study of Cognitive Deficits in Autism Spectrum Disorder}}. {Neuropsychologia};2009 (Jul 3)
In the neuropsychological case series approach, tasks are administered that tap different cognitive domains, and differences within rather than across individuals are the basis for theorising; each individual is effectively their own control. This approach is a mainstay of cognitive neuropsychology, and is particularly suited to the study of populations with heterogeneous deficits. However it has very rarely been applied to the study of cognitive differences in Autism Spectrum Disorder (ASD). Here, we investigate whether this approach can yield information beyond that given by the typical group study method, when applied to an ASD population. Twenty-one high functioning adult ASD participants and twenty-two IQ, age, and gender-matched control participants were administered a large battery of neuropsychological tests that would represent a typical neuropsychological assessment for neurological patients in the United Kingdom. The data were analysed using both group and single case study methods. The group analysis revealed a limited number of deficits, principally on tests with a large executive function component, with no impairment in more routine abilities such as basic attending, language and perception. Single case study analysis proved more fruitful revealing evidence of considerable variation in abilities both between and within ASD participants. Both sub-normal and supra-normal performance was observed, with the most defining feature of the ASD group being this variability. We conclude that the use of group-level analysis alone in the study of cognitive deficits in ASD risks missing cognitive characteristics that may be vitally important both theoretically and clinically, and even may be misleading because of averaging artifact.
