1. Angelidou A, Alysandratos KD, Asadi S, Zhang B, Francis K, Vasiadi M, et al. {{Brief Report: « Allergic Symptoms » in Children with Autism Spectrum Disorders. More than Meets the Eye?}}. {J Autism Dev Disord}. 2011 Jan 6.
Many children with Autism Spectrum Disorders (ASD) have either family and/or personal history of « allergic symptomatology », often in the absence of positive skin or RAST tests. These symptoms may suggest mast cell activation by non-allergic triggers. Moreover, children with mastocytosis or mast cell activation syndrome (MCAS), a spectrum of rare diseases characterized by increased number of activated mast cells in many organs, appear to have ASD at a rate tenfold higher (1/10 children) than that of the general population (1/100 children). Mast cell activation by allergic, infectious, environmental and stress-related triggers, especially perinatally, would release pro-inflammatory and neurotoxic molecules. We speculate these could disrupt the gut-blood-brain barriers, thus contributing to brain inflammation and ASD pathogenesis. Increased mast cell responsiveness may define at least a subgroup of ASD subjects, who could benefit from inhibition of mast cell activation.
2. Belger A, Carpenter KL, Yucel GH, Cleary KM, Donkers FC. {{The Neural Circuitry of Autism}}. {Neurotox Res}. 2011 Jan 7.
Autism is a complex neurodevelopmental disorder, characterized by deficits in social emotional, and language domains, as well as repetitive restrictive behaviors. The vast heterogeneity of the clinical and behavioral symptoms has made it rather difficult to delineate the neural circuitry affiliated with these domains of dysfunction. The current review aims at broadly outlining the latest research into the neurobiology and neural circuitry underlying the core domains of deficits in autism. We further discuss new avenues of research that can further our understanding of the dimensions of this complex disorder.
3. Burstyn I, Wang X, Yasui Y, Sithole F, Zwaigenbaum L. {{Autism spectrum disorders and fetal hypoxia in a population-based cohort: Accounting for missing exposures via Estimation-Maximization algorithm}}. {BMC Med Res Methodol}. 2011 Jan 5;11(1):2.
ABSTRACT: BACKGROUND: Autism spectrum disorders (ASD) are associated with complications of pregnancy that implicate fetal hypoxia (FH); the excess of ASD in male gender is poorly understood. We tested the hypothesis that risk of ASD is related to fetal hypoxia and investigated whether this effect is greater among males. METHODS: Provincial delivery records (PDR) identified the cohort of all 218,890 singleton live births in the province of Alberta, Canada, between 01-01-98 and 12-31-04. These were followed-up for ASD via ICD-9 diagnostic codes assigned by physician billing until 03-31-08. Maternal and obstetric risk factors, including FH determined from blood tests of acidity (pH), were extracted from PDR. The binary FH status was missing in approximately half of subjects. Assuming that characteristics of mothers and pregnancies would be correlated with FH, we used an Estimation-Maximization (E-M) algorithm to estimate HF-ASD association, allowing for both missing-at-random (MAR) and specific not-missing-at-random (NMAR) mechanisms. RESULTS: Data indicated that there was excess risk of ASD among males who were hypoxic at birth, not materially affected by adjustment for potential confounding due to birth year and socio-economic status: OR 1.13, 95%CI: 0.96, 1.33 (MAR assumption). Limiting analysis to full-term males, the adjusted OR under specific NMAR assumptions spanned 95%CI of 1.0 to 1.6. CONCLUSION: Our results are consistent with a weak effect of fetal hypoxia on risk of ASD among males. E-M algorithm is an efficient and flexible tool for modeling missing data in the studied setting.
4. Ey E, Leblond CS, Bourgeron T. {{Behavioral profiles of mouse models for autism spectrum disorders}}. {Autism Res}. 2011 Jan 5.
Autism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and stereotyped verbal and nonverbal behaviors. In approximately 10-25% of the affected individuals, a genetic mutation associated with the condition can be identified. Recently, mutations altering synapse formation, cellular/synaptic growth rate and regulation of excitatory and inhibitory currents were identified in patients with intellectual disability, typical autism, Asperger syndrome or neurological syndromes associated with autistic traits. Following these genetic findings, mouse models carrying mutations similar to those identified in patients have been generated. These models offer the opportunity to investigate in vivo the physiological and behavioral consequences of the mutations. Here, we review the existing data on the phenotypes of mice carrying mutations in genes associated with ASD including neuroligin, neurexin and Shank mutant mice as well as the Fmr1, Mecp2, Ube3a, Nf1, Pten and Tsc1/Tsc2 mutant mice. The diversity and complexity of the phenotype of these mouse models reflect the broad range of phenotypes observed in patients with ASD. Remarkably, results from therapeutic approaches (e.g., modulation of gene expression, administration of pharmacological and nonpharmacological substances, enriched environment) are encouraging since some behavioral alterations could be reversed even when treatment was performed on adult mice. These ongoing studies should therefore increase our understanding of the biological alterations associated with ASD as well as the development of knowledge-based treatments.
5. Ghanizadeh A. {{Targeting of Glycine Site on NMDA Receptor as a Possible New Strategy for Autism Treatment}}. {Neurochem Res}. 2011 Jan 6.
The exact pathophysiology of the neurodevelopment disorder of autism is not clear and there is not any curative approach for it. There is only one FDA-approved medication for its management. Therefore, providing of novel treatments is highly required. The hypofunction of GABAergic system and glutamate toxicity are generally believed to have a causal role for autism. The antagonist of the N-methyl-D: -aspartic acid (NMDA) glutamate receptor improves autism. Glycine is required for the activation of NMDA receptor. The antagonist of glycine site decreases NMDA receptor conductance. It is hypothesis that glycine site antagonists can be tested as a new strategy for the management of autism.
6. Godlee F, Smith J, Marcovitch H. {{Wakefield’s article linking MMR vaccine and autism was fraudulent}}. {BMJ}. 2011;342:c7452.
7. Kulesza RJ, Jr., Lukose R, Stevens LV. {{Malformation of the human superior olive in autistic spectrum disorders}}. {Brain Res}. 2011 Jan 7;1367:360-71.
Autistic spectrum disorders (ASD) comprise a continuum of psychosocial disorders clinically characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Despite the prevalence of ASD, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Further, there is ample evidence that auditory dysfunction is a common feature of autism. Our preliminary investigation of neuronal morphology in the auditory brainstem of individuals with ASD focused on the medial superior olive (MSO) and revealed that neurons in this region were significantly smaller and rounder than in controls. In this report, we expand our investigation to examine all nuclei within the human superior olivary complex (SOC), an important auditory brainstem center. We examine neuronal morphology and neuronal number in four control (average age=15 years) and 9 autistic brains (average age=15 years). This detailed investigation supports our previous descriptions of the MSO, and also reveals significant dysmorphology in five other SOC nuclei. Moreover, we provide evidence of a consistent and significant decrease in the number of SOC neurons in the autistic brain. Our studies implicate an extensive malformation of the auditory brainstem in the hearing and language difficulties in individuals with ASD. The results from this investigation suggest that neonatal testing of auditory function may aid in the identification of individuals with ASD earlier than presently possible.
8. Lee MS, Kim JI, Ernst E. {{Massage therapy for children with autism spectrum disorders: a systematic review}}. {J Clin Psychiatry}. 2010 Dec 28.
OBJECTIVE: We aimed to assess the effectiveness of massage as a treatment option for autism. DATA SOURCES: We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was « (massage OR touch OR acupressure) AND (autistic OR autism OR Asperger’s syndrome OR pervasive developmental disorder). » The references in all located articles were also searched. No language restrictions were imposed. STUDY SELECTION: Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. DATA EXTRACTION: All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. RESULTS: Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. CONCLUSIONS: Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted.
9. White SJ, Coniston D, Rogers R, Frith U. {{Developing the Frith-Happe animations: A quick and objective test of Theory of Mind for adults with autism}}. {Autism Res}. 2011 Jan 5.
It is now widely accepted that individuals with autism have a Theory of Mind (ToM) or mentalizing deficit. This has traditionally been assessed with false-belief tasks and, more recently, with silent geometric animations, an on-line ToM task. In adults with milder forms of autism standard false-belief tests, originally devised for children, often prove insensitive, while the Frith-Happe animations have had rather better success at capturing the on-line ToM deficit in this population. However, analysis of participants’ verbal descriptions of these animations, which span scenarios from « Random » to « Goal-Directed » and « ToM, » is time consuming and subjective. In this study, we developed and established the feasibility of an objective method of response through a series of multiple-choice questions. Sixteen adults with autism and 15 typically developing adults took part, matched for age and intelligence. The adults with autism were less accurate as a group at categorizing the Frith-Happe animations by the presence or absence of mental and physical interactions. Furthermore, they were less able to select the correct emotions that are typically attributed to the triangles in the mental state animations. This new objective method for assessing the understanding of the animations succeeded in being as sensitive as the original subjective method in detecting the mentalizing difficulties in autism, as well as being quicker and easier to administer and analyze.
10. Wing L, Gould J, Gillberg C. {{Autism spectrum disorders in the DSM-V: Better or worse than the DSM-IV?}}. {Res Dev Disabil}. 2011 Jan 3.
The DSM-V-committee has recently published proposed diagnostic criteria for autism spectrum disorders. We examine these criteria in some detail. We believe that the DSM-committee has overlooked a number of important issues, including social imagination, diagnosis in infancy and adulthood, and the possibility that girls and women with autism may continue to go unrecognised or misdiagnosed under the new manual. We conclude that a number of changes need to be made in order that the DSM-V-criteria might be used reliably and validly in clinical practice and research.
