1. Berkel S, Marshall CR, Weiss B, Howe J, Roeth R, Moog U, Endris V, Roberts W, Szatmari P, Pinto D, Bonin M, Riess A, Engels H, Sprengel R, Scherer SW, Rappold GA. {{Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation}}. {Nat Genet} (May 16)
Using microarrays, we identified de novo copy number variations in the SHANK2 synaptic scaffolding gene in two unrelated individuals with autism-spectrum disorder (ASD) and mental retardation. DNA sequencing of SHANK2 in 396 individuals with ASD, 184 individuals with mental retardation and 659 unaffected individuals (controls) revealed additional variants that were specific to ASD and mental retardation cases, including a de novo nonsense mutation and seven rare inherited changes. Our findings further link common genes between ASD and intellectual disability.
2. Daniels AM, Rosenberg RE, Law JK, Lord C, Kaufmann WE, Law PA. {{Stability of Initial Autism Spectrum Disorder Diagnoses in Community Settings}}. {J Autism Dev Disord} (May 15)
The study’s objectives were to assess diagnostic stability of initial autism spectrum disorder (ASD) diagnoses in community settings and identify factors associated with diagnostic instability using data from a national Web-based autism registry. A Cox proportional hazards model was used to assess the relative risk of change in initial ASD diagnosis as a function of demographic characteristics, diagnostic subtype, environmental factors and natural history. Autistic disorder was the most stable initial diagnosis; pervasive developmental disorder-not otherwise specified was the least stable. Additional factors such as diagnosing clinician, region, when in time a child was initially diagnosed, and history of autistic regression also were significantly associated with diagnostic stability in community settings. Findings suggest that the present classification system and other secular factors may be contributing to increasing instability of community-assigned labels of ASD.
3. Dinstein I, Thomas C, Humphreys K, Minshew N, Behrmann M, Heeger DJ. {{Normal Movement Selectivity in Autism}}. {Neuron} (May 13);66(3):461-469.
It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Movement selectivity is a defining characteristic of neurons involved in movement perception, including mirror neurons, and, as such, these findings argue against a mirror system dysfunction in autism. VIDEO ABSTRACT:
4. Hranilovic D, Blazevic S, Babic M, Smurinic M, Bujas-Petkovic Z, Jernej B. {{5-HT(2A) receptor gene polymorphisms in Croatian subjects with autistic disorder}}. {Psychiatry Res} (May 12)
Disturbances in the expression/function of 5-HT(2A) receptor are implicated in autism. Association of 5-HT(2A) receptor gene with autism was studied in the Croatian population. Distribution frequencies for alleles, genotypes and haplotypes of -1438 A/G and His452Tyr polymorphisms were compared in samples of 103 autistic and 214 control subjects. Significant overrepresentation of G allele and GG genotype of -1438 A/G polymorphism was observed in group of autistic subjects, supporting possible involvement of 5-HT(2A) receptor in the development of autism.
5. Lasalle JM, Yasui DH. {{Evolving role of MeCP2 in Rett syndrome and autism}}. {Epigenomics};2009 (Oct 1);1(1):119-130.
Rett syndrome is an X-linked autism-spectrum disorder caused by mutations in MECP2, encoding methyl CpG-binding protein 2. Since the discovery of MECP2 mutations as the genetic cause of Rett syndrome, the understanding of MeCP2 function has evolved. Although MeCP2 was predicted to be a global transcriptional repressor of methylated promoters, large-scale combined epigenomic approaches of MeCP2 binding, methylation and gene expression have demonstrated that MeCP2 binds preferentially to intergenic and intronic regions, and sparsely methylated promoters of active genes. This review compares the evolution of thought within two ‘classic’ epigenetic mechanisms of parental imprinting and X chromosome inactivation to that of the MeCP2 field, and considers the future relevance of integrated epigenomic databases to understanding autism and Rett syndrome.
6. Ozgen H, Hellemann GS, Stellato RK, Lahuis B, van Daalen E, Staal WG, Rozendal M, Hennekam RC, Beemer FA, van Engeland H. {{Morphological Features in Children with Autism Spectrum Disorders: A Matched Case-Control Study}}. {J Autism Dev Disord} (May 15)
This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs. Morphological abnormalities were significantly more prevalent in patients with autism than in the normal control group and 48 morphological features distinguished patients from controls. Our findings show that morphological features are associated with autism. Exploring potential underlying genetic mechanisms of this association might lead to a better understanding of autism.
7. Sevlever M, Gillis JM. {{An examination of the state of imitation research in children with autism: Issues of definition and methodology}}. {Res Dev Disabil} (May 12)
Several authors have suggested that children with autism are impaired in their ability to imitate others. However, diverse methodologies, contradictory findings, and varying theoretical explanations continue to exist in the literature despite decades of research. A comprehensive account of imitation in children with autism is hampered by the lack of a consistent and operational definition of imitation and other more simplistic forms of copying behavior. Failure to adopt specific definitions of imitative behavior and tasks capable of distinguishing between various types of copying behavior may be at the root of contradictions across studies of imitation and the lack of a unified theoretical account of the « imitation deficit » in autism. The current state of imitation research in children with autism is discussed, and specific recommendations are suggested regarding the adoption of a comparative taxonomy of imitation, a standardized methodology across researchers, and a standardized imitation battery for children with autism.
8. Wink LK, Plawecki MH, Erickson CA, Stigler KA, McDougle CJ. {{Emerging drugs for the treatment of symptoms associated with autism spectrum disorders}}. {Expert Opin Emerg Drugs} (May 15)
Importance of the field: Autism spectrum disorders, or pervasive developmental disorders (PDDs), are neurodevelopmental disorders defined by qualitative impairment in social interaction, impaired communication and stereotyped patterns of behavior. The most common forms of PDD are autistic disorder (autism), Asperger’s disorder and PDD not otherwise specified. Recent surveillance studies reveal an increase in the prevalence of autism and related PDDs. The use of pharmacologic agents in the treatment of these disorders can reduce the impact of interfering symptoms, providing relief for affected individuals and their families. Areas covered in this review: This review examines results from neurobiologic research in an attempt to both elucidate the pathophysiology of autism and guide the development of pharmacologic agents for the treatment of associated symptoms. The safety and efficacy data of drugs currently in clinical use for the treatment of these symptoms, as well as pharmaceuticals currently under development, are discussed. What the reader will gain: This comprehensive review will deepen the reader’s current understanding of the research guiding the pharmacologic treatment of symptoms associated with autism and related PDDs. Areas of focus for future research are also discussed. The need for large-scale investigation of some commonly used pharmacologic agents, in addition to the development of drugs with improved efficacy and safety profiles, is made evident. Take home message: Despite progress in the development of pharmacologic treatments for a number of interfering symptom domains associated with autism and other PDDs, a great deal of work remains.
