1. Palmer E, Ketteridge C, Parr JR, Baird G, Le Couteur A. {{Autism spectrum disorder diagnostic assessments: improvements since publication of the National Autism Plan for Children}}. {Arch Dis Child} (Jun 3)
Objectives To assess in the context of a publically funded healthcare system, change in UK autism spectrum disorder (ASD) clinical diagnostic practice following the recommendations of the National Autism Plan for Children (NAP-C 2003). Methods In 2007, a questionnaire based on standards from the NAP-C was sent to UK child development teams (CDTs); results were compared with 2001 data from the National Initiative for Autism Screening and Assessment. Main findings Responses were received from 149 of 243 UK CDTs (61%). Most teams used standardised autism diagnostic assessments. There was greater access to members of the multidisciplinary team than in 2001. Only one-third of teams had a defined timescale for completion of assessment; of those teams, about half met the recommended NAP-C target. Conclusions Since 2001, there has been an improvement in diagnostic services for children with ASD, however, inequalities remain. Providers should continue to improve services in order to deliver timely and comprehensive assessments for children with ASD.
2. Sokhadze E, Baruth J, El-Baz A, Horrell T, Sokhadze G, Carroll T, Tasman A, Sears L, Casanova MF. {{Impaired Error Monitoring and Correction Function in Autism}}. {J Neurother} (Apr 1);14(2):79-95.
INTRODUCTION: Error monitoring and correction is one of the executive functions and is important for effective goal directed behavior. Deficient executive functioning, including reduced error monitoring ability, is one of the typical features of such neurodevelopmental disorders as autism, probably related to perseverative responding, stereotyped repetitive behaviors, and an inability to accurately monitor ongoing behavior. Our prior studies of behavioral and event-related potential (ERP) measures during performance on visual oddball tasks in high-functioning autistic (HFA) children showed that despite only minor differences in reaction times HFA children committed significantly more errors. METHODS: This study investigated error monitoring in children with autism spectrum disorder (ASD) with response-locked event-related potentials – the Error-related Negativity (ERN) and Error-related Positivity (Pe) recorded at fronto-central sites. The ERN reflects early error detection processes, while the Pe has been associated with later conscious error evaluation and attention re-allocation. Reaction times (RT) in correct trials and post-error slowing in reaction times were measured. In this study fourteen subjects with ASD and 14 age- and IQ- matched controls received a three-category visual oddball task with novel distracters. RESULTS: ERN had a lower amplitude and longer latency in the ASD group but was localized in the caudal part of anterior cingulate cortex (ACC) in both groups. The Pe component was significantly prolonged in the ASD group but did not reach significance in amplitude differences compared to controls. We found significant post-error slowing in RTs in controls, and post-error acceleration in RTs in the ASD group. CONCLUSIONS: The reduced ERN and altered Pe along with a lack of post-error RT slowing in autism might be interpreted as insensitivity in the detection and monitoring of response errors and a reduced ability of execute corrective actions. This might result in reduced error awareness and failure in adjustment when dealing with situations where erroneous responses may occur. This deficit might be manifested in the perseverative behaviors often seen in individuals with ASD. The results are discussed in terms of a general impairment in self-monitoring and other executive functions underlying behavioral and social disturbances in ASD.
3. van der Zwaag B, Staal WG, Hochstenbach R, Poot M, Spierenburg HA, de Jonge MV, Verbeek NE, van ‘t Slot R, van Es MA, Staal FJ, Freitag CM, Buizer-Voskamp JE, Nelen MR, van den Berg LH, van Amstel HK, van Engeland H, Burbach JP. {{A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder}}. {Am J Med Genet B Neuropsychiatr Genet} (Jun 5);153B(4):960-966.
High resolution genomic copy-number analysis has shown that inherited and de novo copy-number variations contribute significantly to autism pathology, and that identification of small chromosomal aberrations related to autism will expedite the discovery of risk genes involved. Here, we report a microduplication of chromosome 15q11.2, spanning only four genes, co-segregating with autism in a Dutch pedigree, identified by SNP microarray analysis, and independently confirmed by FISH and MLPA analysis. Quantitative RT-PCR analysis revealed over 70% increase in peripheral blood mRNA levels for the four genes present in the duplicated region in patients, and RNA in situ hybridization on mouse embryonic and adult brain sections revealed that two of the four genes, CYFIP1 and NIPA1, were highly expressed in the developing mouse brain. These findings point towards a contribution of microduplications at chromosome 15q11.2 to autism, and highlight CYFIP1 and NIPA1 as autism risk genes functioning in axonogenesis and synaptogenesis. Thereby, these findings further implicate defects in dosage-sensitive molecular control of neuronal connectivity in autism. However, the prevalence of this microduplication in patient samples was statistically not significantly different from control samples (0.94% in patients vs. 0.42% controls, P = 0.247), which suggests that our findings should be interpreted with caution and indicates the need for studies that include large numbers of control subjects to ascertain the impact of these changes on a population scale.
4. Yang P, Shu BC, Hallmayer JF, Lung FW. {{Intronic Single Nucleotide Polymorphisms of Engrailed Homeobox 2 Modulate the Disease Vulnerability of Autism in a Han Chinese Population}}. {Neuropsychobiology} (Jun 3);62(2):104-115.
Background: Autism is a neurodevelopmental disorder with a strong genetic background that has been suggested to be associated with a susceptibility gene, engrailed homeobox 2(EN2), which maps to chromosome 7q36. Our study was aimed to explore the association between EN2 intronic single nucleotide polymorphisms (SNPs) with autism in an ethnic Han Chinese population. Methods: A total of 193 autism cases and 309 controls were recruited. Five SNPs including rs3824068, rs3824067, rs1861972, rs1861973 and rs3830031 in the intron 1 region were genotyped by using the TaqMan SNP assay. Results: Both the allelic frequencies and genotype distribution of the EN2 intronic SNPs were found to have statistically significant differences between cases and controls, except rs1861972, rs3024067 and rs3824068. According to the constructed linkage disequilibrium plot using genotype data, it was suggested that further haplotypic analyses can be performed on rs3824068, rs1861972 and rs1861973. After completed analyses by the Unphased and Phase programs and logistic regression analysis, one 2-marker haplotype A-C (beta = -2.897; p = 0.013; OR = 0.055) and one 3-marker haplotype G-A-C (beta = -0.491; p = 0.015; OR = 0.612) were identified that were plausibly associated with autism in the ethnic Chinese population. Conclusions: The haplotype A-C of rs1861972 and rs1861973 is the core element of the observed haplotype association in this study, which plays a role as a protective factor against autism; in addition, the haplotype G-A-C is less frequent in male cases compared to controls (38.64 vs. 52.51%), which plausibly modulate disease vulnerability to autism. However, further evidence of the haplotype association of EN2 intronic SNPs and uncertain transcription factor interaction is warranted for further clarification.
