1. Artuso R, Papa FT, Grillo E, Mucciolo M, Yasui DH, Dunaway KW, Disciglio V, Mencarelli MA, Pollazzon M, Zappella M, Hayek G, Mari F, Renieri A, Lasalle JM, Ariani F. {{Investigation of modifier genes within copy number variations in Rett syndrome}}. {J Hum Genet};2011 (May 19)
MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies.Journal of Human Genetics advance online publication, 19 May 2011; doi:10.1038/jhg.2011.50.
2. Berger BE, Navar-Boggan AM, Omer SB. {{Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination – United States, 2001-2010}}. {BMC Public Health};2011 (May 19);11(1):340.
ABSTRACT: BACKGROUND: Congenital rubella syndrome (CRS) is associated with several negative outcomes, including autism spectrum disorders (ASDs). The objective of this study was to estimate the numbers of CRS and ASD cases prevented by rubella vaccination in the United States from 2001 through 2010. METHODS: Prevention estimates were calculated through simple mathematical modeling, with values of model parameters determined from published literature. Model parameters included pre-vaccine era CRS incidence, vaccine era CRS incidence, the number of live births per year, and the percentage of CRS cases presenting with an ASD. RESULTS: Based on our estimates, 16,600 CRS cases (range: 8300-62,250) were prevented by rubella vaccination from 2001 through 2010 in the United States. An estimated 1228 ASD cases were prevented by rubella vaccination in the United States during this time period. Simulating a slight expansion in ASD diagnostic criteria in recent decades, we estimate that a minimum of 830 ASD cases and a maximum of 6225 ASD cases were prevented. CONCLUSIONS: We estimate that rubella vaccination prevented substantial numbers of CRS and ASD cases in the United States from 2001 through 2010. These findings provide additional incentive to maintain high measles-mumps-rubella (MMR) vaccination coverage.
3. Bosl W, Tierney A, Tager-Flusberg H, Nelson C. {{Response: Infant EEG activity as a biomarker for autism: A promising approach or a false promise?}}. {BMC Med};2011 (May 20);9(1):60.
ABSTRACT: Correspondence – no abstract Please see research article: http://www.biomedcentral.com/1741-7015/9/18 and commentary article: http://www.biomedcentral.com/1741-7015/9/61.
4. Finegold SM. {{Desulfovibrio species are potentially important in regressive autism}}. {Med Hypotheses};2011 (May 16)
Autism is a complex disorder with no specific diagnostic test so the disease is defined by its characteristics including cognitive defects, social, communication and behavioral problems, repetitive behaviors, unusual sensitivity to stimuli such as noise, restricted interests, and self stimulation. The incidence of this disease has increased remarkably in recent years and was 110/10,000 children ( approximately 1%) in multiple areas of the US in 2007. The financial burden on families and communities is enormous. In terms of predisposing factors, heredity plays a role in some subjects, but it is clear that environmental factors are also important. Environmental toxins can affect the immune system adversely. Intestinal bacteria are recognized by a few investigators as potentially important and we have proposed that certain antimicrobial drugs may be a key factor in modifying the intestinal bacterial flora adversely, selecting out potentially harmful bacteria that are normally suppressed by an intact normal intestinal flora. We had felt that clostridia in the gut might be involved in autism because they are virulent organisms and spore-formers; spores would resist antibacterial agents so that when antibiotics were discontinued the spores would germinate and by toxin production or another mechanism lead to autism. However, a recent study of ours employing the powerful pyrosequencing technique on stools of subjects with regressive autism showed that Desulfovibrio was more common in autistic subjects than in controls. We subsequently confirmed this with pilot cultural and real-time PCR studies and found siblings of autistic children had counts of Desulfovibrio that were intermediate, suggesting possible spread of the organism in the family environment. Desulfovibrio is an anaerobic bacillus that does not produce spores but is nevertheless resistant to aerobic and other adverse conditions by other mechanisms and is commonly resistant to certain antimicrobial agents (such as cephalosporins) often used to treat ear and other infections that are relatively common in childhood. This bacterium also produces important virulence factors and its physiology and metabolism position it uniquely to account for much of the pathophysiology seen in autism. If these results on Desulfovibrio are confirmed and extended in other studies, including treatment trials with appropriate agents and careful clinical and laboratory studies, this could lead to more reliable classification of autism, a diagnostic test and therapy for regressive autism, development of a vaccine for prevention and treatment of regressive autism, tailored probiotics/prebiotics, and important epidemiologic information.
5. Frye RE, Sreenivasula S, Adams JB. {{Traditional and non-traditional treatments for autism spectrum disorder with seizures: an on-line survey}}. {BMC Pediatr};2011 (May 18);11(1):37.
ABSTRACT: BACKGROUND: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey. METHODS: Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects. RESULTS: Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors. For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments. CONCLUSION: Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.
6. Green SA, Carter AS. {{Predictors and Course of Daily Living Skills Development in Toddlers with Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (May 20)
Self-sufficiency is central to child and family well-being. This report focuses on predictors of adaptive daily living skills (DLS) development in young children with ASD and whether DLS gains predict decreases in parenting stress. Participants were 162 toddlers with ASD and their parents, assessed at 3 annual timepoints. Hierarchical Linear Models showed that age, DQ, and autism symptom severity uniquely predicted initial DLS and DLS growth. Child problem behaviors predicted initial DLS only. DLS was associated with change in parenting stress above and beyond DQ, autism symptom severity, and problem behaviors. Children with lower IQ and more severe symptoms showed slower DLS gains. Given its relation to parenting stress, DLS are an important intervention target in young children with ASD.
7. Griffin R, Westbury C. {{Infant EEG activity as a biomarker for autism: A promising approach or a false promise?}}. {BMC Med};2011 (May 20);9(1):61.
ABSTRACT: The ability to determine an infant’s likelihood of developing autism via a relatively simple neurological measure would constitute an important scientific breakthrough. In their recent publication in this journal, Bosl and colleagues claim that a measure of EEG complexity can be used to detect, with very high accuracy, infants at high risk for autism (HRA). On the surface, this appears to be that very scientific breakthrough and as such the paper has received widespread media attention. But a close look at how these high accuracy rates were derived tells a very different story. This stems from a conflation between « high risk » as a population-level property and « high risk » as a property of an individual. We describe the approach of Bosl et al and examine their results with respect to baseline prevalence rates, the inclusion of which is necessary to distinguish infants with a biological risk of autism from typically developing infants with a sibling with autism. This is an important distinction that should not be overlooked. Please see research article: http://www.biomedcentral.com/1741-7015/9/18 and correspondence article: http://www.biomedcentral.com/1741-7015/9/60.
8. Shih P, Keehn B, Oram JK, Leyden KM, Keown CL, Muller RA. {{Functional Differentiation of Posterior Superior Temporal Sulcus in Autism: A Functional Connectivity Magnetic Resonance Imaging Study}}. {Biol Psychiatry};2011 (May 20)
BACKGROUND: Socio-communicative impairments are salient features of autism spectrum disorder (ASD). Abnormal development of posterior superior temporal sulcus (pSTS)-a key processing area for language, biological motion, and social context-could play a role in these deficits. METHODS: Functional connectivity magnetic resonance imaging was used to examine the synchronization of low-frequency blood oxygen level-dependent fluctuations during continuous performance on a visual search task. Twenty-one children and adolescents with ASD and 26 typically developing individuals-matched on age and IQ-participated in the study. Three subregions of pSTS were delineated with a data-driven approach, and differentiation of pSTS was examined by comparing the connectivity of each subregion. RESULTS: In typically developing individuals, differentiation of networks was positively associated with age and anatomical maturation (cortical thinning in pSTS, greater white matter volume). In the ASD group, differentiation of pSTS connectivity was significantly reduced, and correlations with anatomical measures were weak or absent. Moreover, pSTS differentiation was inversely correlated with autism symptom severity. CONCLUSIONS: Atypical maturation of pSTS suggests altered trajectories for functional segregation and integration of networks in ASD, potentially related to impaired cognitive and sensorimotor development. Furthermore, our findings provide a novel explanation for atypically increased connectivity in ASD that has been observed in some functional connectivity magnetic resonance imaging studies.
9. Stein LI, Polido JC, Mailloux Z, Coleman GG, Cermak SA. {{Oral care and sensory sensitivities in children with autism spectrum disorders}}. {Spec Care Dentist};2011 (May);31(3):102-110.
Children with autism spectrum disorders (ASD) are at high risk for oral disease. The aim of this study was to examine the contribution of sensory processing problems to challenges in receiving oral care for children with ASD. A questionnaire was sent to the parents of 206 children with disabilities to test the hypotheses that children with ASD, relative to children with other disabilities, experience greater difficulty with home-based and professional oral care, and that these difficulties may relate in part to sensory processing problems. The results partially supported these hypotheses. Compared to children with other disabilities, those with ASD had greater behavioral difficulties and sensory sensitivities that parents believed interfered with their child’s oral care. Among children with ASD, sensory sensitivities were associated with oral care difficulties in the home and dental office, and with behavioral difficulties in the dental office. Utilizing strategies to modify the sensory environment may help facilitate oral care in children with ASD.
10. Talero-Gutierrez C, Rodriguez M, De La Rosa D, Morales G, Velez-Van-Meerbeke A. {{Profile of children and adolescents with autism spectrum disorders in an institution in Bogota, Colombia}}. {Neurologia};2011 (May 16)
OBJECTIVE: To determine the profile of children and adolescents diagnosed with autism spectrum disorder (ASD) in a comprehensive care centre in Bogota, Colombia. MATERIAL AND METHODS: A descriptive-correlational study with a sample of patients who had attended the institution from 2003 to 2009. Demographic and clinical aspects were evaluated and a correlation between the diagnosis and severity being analysed in search for risk factors. RESULTS: A total of138 patients were studied. The average age of onset was 21 months, and diagnosis had been made at 45 months. There was a male predominance (6.15:1). The predominant diagnosis was autistic syndrome (83%), followed by pervasive developmental disorder not otherwise specified (17%). There was no pathological background in the family history, during pregnancy or during the neonatal period. Motor development during the first year was normal but acquisition of language skills was compromised. The specific signs of ASD as regards the disorder in itself, communication skills, spontaneous speech, verbal comprehension, attention, imitation, use of objects, self-care and symbolic play were significantly related to the severity of the disease. CONCLUSIONS: Diagnosis of ASD is still delayed in our population and usually after referral from someone other than a health professional. The most important problems were found in communication skills and relationships with peers. The study did not show significant associated risk factors.
11. Tsiaras V, Simos PG, Rezaie R, Sheth BR, Garyfallidis E, Castillo EM, Papanicolaou AC. {{Extracting biomarkers of autism from MEG resting-state functional connectivity networks}}. {Comput Biol Med};2011 (May 16)
The present study is a preliminary attempt to use graph theory for deriving distinct features of resting-state functional networks in young adults with autism spectrum disorder (ASD). Networks modeled neuromagnetic signal interactions between sensors using three alternative interdependence measures: (a) a non-linear measure of generalized synchronization (robust interdependence measure [RIM]), (b) mutual information (MI), and (c) partial directed coherence (PDC). To summarize the information contained in each network model we employed well-established global graph measures (average strength, assortativity, clustering, and efficiency) as well as graph measures (average strength of edges) tailored to specific hypotheses concerning the spatial distribution of abnormalities in connectivity among individuals with ASD. Graph measures then served as features in leave-one-out classification analyses contrasting control and ASD participants. We found that combinations of regionally constrained graph measures, derived from RIM, performed best, discriminating between the two groups with 93.75% accuracy. Network visualization revealed that ASD participants displayed significantly reduced interdependence strength, both within bilateral frontal and temporal sensors, as well as between temporal sensors and the remaining recording sites, in agreement with previous studies of functional connectivity in this disorder.
