1. Benton TD. {{Aripiprazole to treat irritability associated with autism: a placebo-controlled, fixed-dose trial}}. {Curr Psychiatry Rep};2011 (Apr);13(2):77-79.
2. Brendel C, Belakhov V, Werner H, Wegener E, Gartner J, Nudelman I, Baasov T, Huppke P. {{Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model}}. {J Mol Med};2011 (Apr);89(4):389-398.
Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Readthrough of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2 ( R168X ) mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients.
3. Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, Chauhan V. {{Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism}}. {J Neurochem};2011 (Apr);117(2):209-220.
J. Neurochem. (2011) 117, 209-220. ABSTRACT: Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, that is, complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4-10 years) and Group B (adults, ages 14-39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p < 0.05), of complex I in the frontal cortex (p < 0.05), and of complexes II (p < 0.01), III (p < 0.01), and V (p < 0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, that is, 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood.
4. Chien IC, Lin CH, Chou YJ, Chou P. {{Prevalence and Incidence of Autism Spectrum Disorders Among National Health Insurance Enrollees in Taiwan from 1996 to 2005}}. {J Child Neurol};2011 (Apr 1)
The authors used a national database to examine the prevalence and incidence of autism spectrum disorders. The National Health Research Institute provided a database of 1 000 000 random participants for study. A population-based sample of 372 642 aged younger than 18 was obtained as a dynamic cohort. Those study participants who had at least one service claim from 1996 to 2005 with a principal diagnosis of autism spectrum disorders were identified. The cumulative prevalence of autism spectrum disorders increased from 1.79 to 28.72 per 10 000 from 1996 to 2005. The annual incidence of autism spectrum disorders increased from 0.91 to 4.41 per 10 000 per year from 1997 to 2005. Higher incidence was detected in the 0 to 5 age group, in males, and in those who lived in northern, southern, and eastern regions and urban areas. Our findings suggest increases in the prevalence and incidence of treated autism spectrum disorders in Taiwan.
5. Cohen I, Liu X, Lewis M, Chudley A, Forster-Gibson C, Gonzalez M, Jenkins E, Brown W, Holden J. {{Autism severity is associated with child and maternal MAOA genotypes}}. {Clin Genet};2011 (Apr);79(4):355-362.
Cohen IL, Liu X, Lewis MES, Chudley A, Forster-Gibson C, Gonzalez M, Jenkins EC, Brown WT, Holden JJA. Autism severity is associated with child and maternal MAOA genotypes. We replicated and extended a previously reported association between autism severity and a functional polymorphism in the monoamine oxidase A (MAOA) promoter region, MAOA-uVNTR, in a sample of 119 males, aged 2-13 years, with autism spectrum disorder from simplex families. We demonstrated that (i) boys with the low activity 3-repeat MAOA allele had more severe sensory behaviors, arousal regulation problems, and aggression, and worse social communication skills than males with the high activity allele; and (ii) problems with aggression, as well as with fears and rituals, were modified by the mothers’ genotype. Boys with the 4-repeat high activity allele who had homozygous 4-repeat mothers showed increased severity of these behaviors relative to those born to heterozygous mothers. These findings indicate the importance of considering maternal genotype in examining associations of MAOA and other genes with behavior in male offspring.
6. Corbett BA, Gunther JR, Comins D, Price J, Ryan N, Simon D, Schupp CW, Rios T. {{Brief report: theatre as therapy for children with autism spectrum disorder}}. {J Autism Dev Disord};2011 (Apr);41(4):505-511.
The pilot investigation evaluated a theatrical intervention program, Social Emotional NeuroScience Endocrinology (SENSE) Theatre, designed to improve socioemotional functioning and reduce stress in children with autism spectrum disorder (ASD). Eight children with ASD were paired with typically developing peers that served as expert models. Neuropsychological, biological (cortisol and oxytocin), and behavioral measures were assessed in a pretest-posttest design. The intervention was embedded in a full musical theatrical production. Participants showed some improvement in face identification and theory of mind skills. The intervention shows potential promise in improving the socioemotional functioning in children with ASD through the utilization of peers, video and behavioral modeling, and a community-based theatrical setting.
7. de Marchena A, Eigsti IM, Worek A, Ono KE, Snedeker J. {{Mutual exclusivity in autism spectrum disorders: testing the pragmatic hypothesis}}. {Cognition};2011 (Apr);119(1):96-113.
While there is ample evidence that children treat words as mutually exclusive, the cognitive basis of this bias is widely debated. We focus on the distinction between pragmatic and lexical constraints accounts. High-functioning children with autism spectrum disorders (ASD) offer a unique perspective on this debate, as they acquire substantial vocabularies despite impoverished social-pragmatic skills. We tested children and adolescents with ASD in a paradigm examining mutual exclusivity for words and facts. Words were interpreted contrastively more often than facts. Word performance was associated with vocabulary size; fact performance was associated with social-communication skills. Thus mutual exclusivity does not appear to be driven by pragmatics, suggesting that it is either a lexical constraint or a reflection of domain-general learning processes.
8. Dufour-Rainfray D, Vourc’h P, Tourlet S, Guilloteau D, Chalon S, Andres CR. {{Fetal exposure to teratogens: Evidence of genes involved in autism}}. {Neurosci Biobehav Rev};2011 (Apr);35(5):1254-1265.
Environmental challenges during the prenatal period can result in behavioral abnormalities and cognitive deficits that appear later in life such as autism. Prenatal exposure to valproic acid, ethanol, thalidomide and misoprostol has been shown to be associated with an increased incidence of autism. In addition, rodents exposed in utero to some of these drugs show autism-like abnormalities, including brain changes and lifelong behavior dysfunction. Our aim is to summarize current understanding of the relationship between in utero exposure to these drugs and autism in humans and in autism-like animal model phenotypes. It also highlights the importance of these models to understanding the neurobiology of autism, particularly in the identification of susceptibility genes. These drugs are able to modulate the expression of many genes involved in processes such as proliferation, apoptosis, neuronal differentiation and migration, synaptogenesis and synaptic activity. It seems essential to focus research on genes expressed during early neurodevelopment which may be the target of mutations or affected by drugs such as those included in this review.
9. Gargaro BA, Rinehart NJ, Bradshaw JL, Tonge BJ, Sheppard DM. {{Autism and ADHD: How far have we come in the comorbidity debate?}}. {Neurosci Biobehav Rev};2011 (Apr);35(5):1081-1088.
The potential for the coexistence of the developmental disorders autism and attention-deficit/hyperactivity disorder (ADHD) in any one individual has for a long time been a contentious issue. While from a neurobiological perspective it is possible, and even highly likely, that ADHD and autism might clinically co-exist, our major diagnostic classification systems (DSM-IV-TR and ICD-10) currently preclude such a dual-diagnosis. The aim of the current review is to summarise current diagnostic criteria and treatment strategies for the two disorders, relevant theories of developmental dysfunction, and update the state of the debate regarding comorbidity. Evidence from clinical, neuroimaging and neuropsychological domains is considered, and similarities and differences between the two disorders are identified. Suggestions for future research into the comorbid profiles of these disorders are proposed, with a strong emphasis placed on the neuropsychological assessment of executive functioning as a potentially useful tool for both identifying similarities, and differentiating the disorders.
10. Harada M, Taki MM, Nose A, Kubo H, Mori K, Nishitani H, Matsuda T. {{Non-Invasive Evaluation of the GABAergic/Glutamatergic System in Autistic Patients Observed by MEGA-Editing Proton MR Spectroscopy Using a Clinical 3 Tesla Instrument}}. {J Autism Dev Disord};2011 (Apr);41(4):447-454.
Amino acids related to neurotransmitters and the GABAergic/glutamatergic system were measured using a 3 T-MRI instrument in 12 patients with autism and 10 normal controls. All measurements were performed in the frontal lobe (FL) and lenticular nuclei (LN) using a conventional sequence for n-acetyl aspartate (NAA) and glutamate (Glu), and the MEGA-editing method for GABA. The GABA level and [GABA]/[NAA] ratio were significantly lower (p < 0.01) in the FL, but not the LN, in patients with autism compared to normal controls. The [GABA]/[Glu] ratio in the FL was also significantly lower (p < 0.05) in the patients than in the normal controls, thus suggesting a possible abnormality in the regulation between GABA and Glu.
11. Jarquin VG, Wiggins LD, Schieve LA, Van Naarden-Braun K. {{Racial disparities in community identification of autism spectrum disorders over time; metropolitan atlanta, georgia, 2000-2006}}. {J Dev Behav Pediatr};2011 (Apr);32(3):179-187.
OBJECTIVE: : Past research indicates that non-Hispanic black (NHB) children are less likely than non-Hispanic white (NHW) children to have an autism spectrum disorder (ASD) diagnosis, even if they seem to meet criteria for the disorder. This study examined differences in community identification of ASDs between NHB and NHW children identified by a population-based surveillance system. METHODS: : Participants were identified as an ASD surveillance case by the Metropolitan Atlanta Developmental Disabilities Surveillance Program in surveillance years 2000, 2002, 2004, and 2006. Health and education records were abstracted and reviewed to determine ASD surveillance case status; community identification was defined by a documented ASD diagnosis, special education eligibility, and behaviors noted in records. Children were placed in 1 of 5 mutually exclusive categories on the basis of ASD specificity. RESULTS: : Total ASD prevalence was higher for NHW than NHB children, but NHB children were more likely than NHW children to have autistic disorder and autism eligibility at a public school documented in records. NHB children were less likely than NHW children to have pervasive developmental disorder-not otherwise specified and Asperger’s disorder documented in records, even after controlling for socioeconomic status. NHB children were more likely than NHW children to have co-occurring intellectual disability. CONCLUSION: : NHB children were less likely than NHW children to have been identified with less severe ASDs, which might have prevented or delayed intervention services that would have catered to their needs. This study illustrates the need for continued professional education, particularly concerning milder ASDs in minority groups.
12. Jefferson AL, Woodhead HJ, Fyfe S, Briody J, Bebbington A, Strauss BJ, Jacoby P, Leonard H. {{Bone Mineral Content and Density in Rett Syndrome and Their Contributing Factors}}. {Pediatr Res};2011 (Apr);69(4):293-298.
This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and to assess how factors such as genotype, epilepsy, BMI, and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy x-ray absorptiometry. Mean height standardized Z scores and CIs for the bone outcomes were obtained from multiple regression models. The mean height Z score for the FN aBMD was low at -2.20, while the LS aBMD was -0.72. The TBBMC mean height Z score was -0.62, although once adjusted for BA and LTM, the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168x and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relationship between genotype, BMC, and aBMD is likely underpinned by the strong relationship between LTM, mobility, and bone outcome measures. ABBREVIATIONS::
13. Jeste SS. {{The neurology of autism spectrum disorders}}. {Curr Opin Neurol};2011 (Apr);24(2):132-139.
PURPOSE OF REVIEW: Neurological comorbidities in autism spectrum disorders (ASDs) are not only common, but they are also associated with more clinical severity. This review highlights the most recent literature on three of autism’s most prevalent neurological comorbidities: motor impairment, sleep disorders and epilepsy. RECENT FINDINGS: Motor impairment in ASDs manifests as both delays and deficits, with delays found in gross and fine motor domains and deficits found in praxis, coordination and gait, all of which affect other cognitive and behavioral domains. Sleep disorders, especially insomnia, occur in up to 83% of children with ASDs and recent studies have begun to explore the underlying biochemical and behavioral basis of the impairment, which has bolstered treatment studies. Epilepsy is reported in up to one third of children with ASDs, and new studies have focused on identifying the genetic causes of this association. SUMMARY: Better characterization of the phenotype, developmental trajectory and underlying pathophysiology of these neurological comorbidities will enable us to define neurological endophenotypes within the autism spectrum. Future studies must investigate the emergence of these comorbidities prospectively in order to determine whether they lie on the causal pathway to ASDs or whether they reflect epiphenomena of the disorder. As epilepsy and sleep disorders can be treated and may contribute significantly to behavioral and cognitive abnormalities in ASDs, their identification is of high clinical relevance.
14. Jones CR, Happe F, Pickles A, Marsden AJ, Tregay J, Baird G, Simonoff E, Charman T. {{‘Everyday memory’ impairments in autism spectrum disorders}}. {J Autism Dev Disord};2011 (Apr);41(4):455-464.
‘Everyday memory’ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children’s Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed.
15. Kalkbrenner AE, Daniels JL, Emch M, Morrissey J, Poole C, Chen JC. {{Geographic access to health services and diagnosis with an autism spectrum disorder}}. {Ann Epidemiol};2011 (Apr);21(4):304-310.
PURPOSE: To assess the impact of geographic health services factors on the timely diagnosis of autism. METHODS: Children residing in central North Carolina were identified by records-based surveillance as meeting a standardized case definition for autism. Individual-level geographic access to health services was measured by the density of providers likely to diagnose autism, distance to early intervention service agencies and medical schools, and residence within a Health Professional Shortage Area. We compared the presence of an autism diagnosis by age 8 and timing of first diagnosis across level of accessibility, using Poisson regression and Cox proportional hazards regression and adjusting for family and neighborhood characteristics. RESULTS: Of 206 identified cases, 23% had no previous documented diagnosis of autism. Most adjusted estimates had confidence limits including the null. Point estimates across analyses suggested that younger age at diagnosis was found for areas with many neurologists and psychiatrists and proximal to a medical school but not areas with many primary care physicians or proximal to early intervention services agencies. CONCLUSIONS: Further study of the distribution of medical specialists diagnosing autism may suggest interventions to promote the early diagnosis, and initiation of targeted services, for children with autism spectrum disorders.
16. Kamen BA, Chukoskie L. {{Autism Speaks: Meeting on Folate Metabolism and Autism Spectrum Disorders, March 19-20, 2009, Washington, DC}}. {J Pediatr Hematol Oncol};2011 (Apr);33(3):208-215.
17. Koh HC, Milne E. {{Evidence for a Cultural Influence on Field-Independence in Autism Spectrum Disorder}}. {J Autism Dev Disord};2011 (Apr 1)
Field-independence, or weak central coherence, is a recognised phenotype of autism spectrum disorder (ASD). There is also evidence of cultural variation in this perceptual style, as neurotypical individuals from Western nations are more field-independent than neurotypical individuals from East-Asian nations. The majority of research on perceptual style in those with ASD has been carried out in Western nations therefore it is unclear whether increased field-independence in ASD is a culturally universal phenotype. Here, we assessed perceptual style in children with and without ASD from England and Singapore using the Children’s Embedded Figures Test and the Framed-Line Test. We found increased field-independence in the English participants with ASD only, suggesting that weak central coherence in ASD is not culturally universal.
18. Korvatska O, Estes A, Munson J, Dawson G, Bekris LM, Kohen R, Yu CE, Schellenberg GD, Raskind WH. {{Mutations in the TSGA14 gene in families with autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Apr);156(3):303-311.
Linkage to 7q has been the most robust genetic finding in familial autism. A previous scan of multiplex families with autism spectrum disorders found a linkage signal of genome-wide significance at D7S530 on 7q32. We searched a candidate imprinted region at this location for genetic variants in families with positive linkage scores. Using exon resequencing, we identified three rare potentially pathogenic variants in the TSGA14 gene, which encodes a centrosomal protein. Two variants were missense mutations (c.664C>G; p.P206A and c.766T>G; p.C240G) that changed conserved residues in the same protein domain; the third variant (c.192+5G>A) altered splicing, which resulted in a protein with an internal deletion of 16 residues and a G33D substitution. These rare TSGA14 variants are enriched in the affected subjects (6/348 patients versus 2/670 controls, Fisher’s exact two tailed P = 0.022). This is the first report of a possible link of a gene with a centrosomal function with familial autism. (c) 2011 Wiley-Liss, Inc.
19. Leu RM, Beyderman L, Botzolakis EJ, Surdyka K, Wang L, Malow BA. {{Relation of melatonin to sleep architecture in children with autism}}. {J Autism Dev Disord};2011 (Apr);41(4):427-433.
Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4-10 years, completed two nights of polysomnography and one overnight urine collection for measurement of urinary 6-SM excretion rate. Parents completed the Children’s Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates were associated with increased N3 sleep, decreased N2 sleep, and decreased daytime sleepiness. The results warrant further examination to examine the effects of supplemental melatonin on sleep architecture and daytime sleepiness.
20. Meindl JN, Cannella-Malone HI. {{Initiating and responding to joint attention bids in children with autism: A review of the literature}}. {Res Dev Disabil};2011 (Mar 28)
Joint attention is a skill that involves coordinating the attention of at least two individuals towards an object or event. Although it is seen as a critical skill in early child development, it is frequently absent in children with autism and has been linked to poorer language outcomes for those children. As a result, multiple interventions have been developed to teach children with autism to respond to, and initiate, bids for joint attention. These interventions, however, differ widely both in terms of procedures used and in whether they focus on teaching children to respond to, or initiate, bids for joint attention. This literature review was conducted to document research gaps and intervention similarities between joint attention intervention studies for children with autism. The specific intent of this review was to determine whether researchers teach responding and initiating separately or sequentially, describe the extent to which procedures differ among studies, and identify whether social or non-social consequences are used during joint attention training. Implications for the treatment of joint attention deficits are discussed and recommendations to both researchers and practitioners are provided.
21. Merchan-Naranjo J, Mayoral M, Rapado-Castro M, Llorente C, Boada L, Arango C, Parellada M. {{Estimation of the Intelligence Quotient Using Wechsler Intelligence Scales in Children and Adolescents with Asperger Syndrome}}. {J Autism Dev Disord};2011 (Apr 1)
Asperger syndrome (AS) patients show heterogeneous intelligence profiles and the validity of short forms for estimating intelligence has rarely been studied in this population. We analyzed the validity of Wechsler Intelligence Scale (WIS) short forms for estimating full-scale intelligence quotient (FSIQ) and assessing intelligence profiles in 29 AS patients. Only the Information and Block Design dyad meets the study criteria. No statistically significant differences were found between dyad scores and FSIQ scores (t(28) = 1.757; p = 0.09). The dyad has a high correlation with FSIQ, good percentage of variance explained (R (2) = 0.591; p < 0.001), and high consistency with the FSIQ classification (chi (2)(36) = 45.202; p = 0.14). Short forms with good predictive accuracy may not be accurate in clinical groups with atypical cognitive profiles such as AS patients.
22. Miles JH. {{Autism spectrum disorders-A genetics review}}. {Genet Med};2011 (Apr);13(4):278-294.
Autism is an etiologically and clinically heterogeneous group of disorders, diagnosed solely by the complex behavioral phenotype. On the basis of the high-heritability index, geneticists are confident that autism will be the first behavioral disorder for which the genetic basis can be well established. Although it was initially assumed that major genome-wide and candidate gene association studies would lead most directly to common autism genes, progress has been slow. Rather, most discoveries have come from studies of known genetic disorders associated with the behavioral phenotype. New technology, especially array chromosomal genomic hybridization, has both increased the identification of putative autism genes and raised to approximately 25%, the percentage of children for whom an autism-related genetic change can be identified. Incorporating clinical geneticists into the diagnostic and autism research arenas is vital to the field. Interpreting this new technology and deciphering autism’s genetic montage require the skill set of the clinical geneticist including knowing how to acquire and interpret family pedigrees, how to analyze complex morphologic, neurologic, and medical phenotypes, sorting out heterogeneity, developing rational genetic models, and designing studies. The current emphasis on deciphering autism spectrum disorders has accelerated the field of neuroscience and demonstrated the necessity of multidisciplinary research that must include clinical geneticists both in the clinics and in the design and implementation of basic, clinical, and translational research.
23. Nucaro A, Pisano T, Chillotti I, Montaldo C, Pruna D. {{Chromosome 8p23.2-pter: a critical region for mental retardation, autism and epilepsy?}}. {Clin Genet};2011 (Apr);79(4):394-395.
24. Pang KH, Croaker GD. {{Constipation in children with autism and autistic spectrum disorder}}. {Pediatr Surg Int};2011 (Apr);27(4):353-358.
BACKGROUND: Children with autistic spectrum disorders (ASDs) have long been known to suffer from GIT symptoms. We planned to quantify the contribution of this group to our constipation clinic workload, and to discover defining group characteristics. METHODS: The characteristics of the bowel habit of children with autism +/- neuro-developmental psychiatric (NDP) diagnoses were compared with ‘normal’ children by retrospective chart review. Data were entered into an Excel spreadsheet (Microsoft Office 2007), and compared between groups. RESULTS: One hundred and eighteen patients presented to the Paediatric Surgical Constipation clinic between April 2003 and May 2008. 90 patients were otherwise normal; 18 patients had NDP; 6 patients had ASD alone and 4 had ASD with other neurodevelopmental features. The median [interquartile range] age at onset in the ASD + NDP and normal groups was 2.5 (1-6) and 14 (4-36) months, respectively (p = 0.03) and the median duration of history in the ASD +/- NDP and normal groups was 61 (47-89) and 27 (13-53) months, respectively (p = 0.007). CONCLUSIONS: Autism spectrum disorders are an order of magnitude more common in the constipation clinic than in the general population. 8.5% of patients who attended our Paediatric Surgical Constipation clinic had autism with or without NDP deficits. Children with autism +/- NDP deficits have an earlier onset of symptoms, longer history, and some possess signs similar to those of slow transit constipation. These features may be inborn. A common genetic origin of gut and behavioural abnormalities suggests that specific targeted investigation and treatment for the constipation of ASD may in time be developed.
25. Pecorelli A, Ciccoli L, Signorini C, Leoncini S, Giardini A, D’Esposito M, Filosa S, Hayek J, De Felice C, Valacchi G. {{Increased levels of 4HNE-protein plasma adducts in Rett syndrome}}. {Clin Biochem};2011 (Apr);44(5-6):368-371.
OBJECTIVE: Rett syndrome (RTT) is a neurological disorder and a leading cause of mental retardation in females. It is caused by mutations in methyl-CpG-binding protein 2 (MeCP2) gene and more rarely in cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1) genes. Increased oxidative stress (OS) has been documented in MeCP2-RTT patients. Here, we evaluated the levels of 4-hydroxynonenal plasma protein adducts (4HNE-PAs) in MeCP2-, CDKL5-, and FOXG1-RTT and in their clinical variants. DESIGN AND METHODS: 4HNE-PAs were determined by Western blot in plasma from healthy subjects and RTT patients. RESULTS: 4HNE-PAs levels were increased in MeCP2- and CDKL5-related RTT but not in FOXG1-related RTT. CONCLUSION: These results showed that OS is present in RTT clinical variants and could play a key role in RTT pathogenesis. Under the OS point of view FOXG1-related RTT appears to be distinct from the MeCP2/CDKL5, suggesting a distinct mechanism involved in its pathogenesis.
26. Phelan HL, Filliter JH, Johnson SA. {{Brief Report: Memory Performance on the California Verbal Learning Test – Children’s Version in Autism Spectrum Disorder}}. {J Autism Dev Disord};2011 (Apr);41(4):518-523.
According to the Task Support Hypothesis (TSH; Bowler et al. in Neuropsychologia 35:65-70, 1997) individuals with autism spectrum disorder (ASD) perform more similarly to their typically developing peers on learning and memory tasks when provided with external support at retrieval. We administered the California Verbal Learning Test-Children’s Version to 15 high-functioning youths with ASD and 15 matched comparison participants. Although ASD and comparison participants had comparable levels of overall performance, the ASD group, but not the comparison group, improved significantly from free to cued recall, providing support for the TSH. These results indicate that verbal memory performance in youths with ASD is relatively intact, but may be facilitated by external supports.
27. Rahbar MH, Ibrahim K, Assassi P. {{Knowledge and attitude of general practitioners regarding autism in karachi, pakistan}}. {J Autism Dev Disord};2011 (Apr);41(4):465-474.
General practitioners (GPs) could have an important role in early diagnosis of autism. There have been no studies evaluating the knowledge of GPs regarding autism in Pakistan. We aimed to fill that gap by assessing knowledge and attitude of GPs in Karachi regarding autism. We conducted a cross-sectional survey of 348 GPs; only 148 (44.6%) had heard of « autism. » Our results show that GPs less than 30 years of age and those who obtained their Medical Degree in the last 5 years are more likely to report knowledge about autism: OR = 3.0; 95% CI: 1.71, 5.31, and OR = 2.56; 95% CI: 1.48, 4.42, respectively. In addition, among those reporting knowledge about autism, many held misconceptions regarding the signs and symptoms and etiology.
28. Robinson EB, Munir K, Munafo MR, Hughes M, McCormick MC, Koenen KC. {{Stability of autistic traits in the general population: further evidence for a continuum of impairment}}. {J Am Acad Child Adolesc Psychiatry};2011 (Apr);50(4):376-384.
OBJECTIVE: This study investigated the developmental course of autistic traits in a nationally representative sample of subjects 7 to 13 years of age. METHOD: The parents of 6,539 children in the Avon Longitudinal Study of Parents and Children completed the Social and Communication Disorders Checklist at ages 7, 10, and 13. The phenotypic progression of autistic traits was assessed in the full sample and in high-scoring individuals (e.g., top 10%, 5%). Gender, IQ, and overall behavior difficulties were examined as potentially relevant influences on autistic trait trajectories. RESULTS: Autistic traits were highly stable in the general population overall and in the high-scoring groups. In the full sample, there was no change in mean Social and Communication Disorders Checklist scores for female subjects ages 7 to 13 (p = .43). Scores for male subjects decreased slightly, but significantly, on the order of 0.1 standard deviations (p < .001). There was no mean change in parent-rated autistic traits within any of the high-scoring groups. IQ was not related to phenotypic progression; high parent-rated behavior problems predicted slight improvement in Social and Communication Disorders Checklist scores over the course of the study period in high-scoring individuals (p < .01). CONCLUSIONS: These findings suggest that autistic traits are highly stable in the general population, even in individuals with the highest concentrations of autism-like behaviors. Phenotypic stability is consistent with expectations for individuals with autism spectrum disorders, providing further support for a phenomenologic continuum across the clinical threshold. Moreover, the gap between female and male risk for autistic symptomology is consistent over time.
29. Roende G, Ravn K, Fuglsang K, Andersen H, Vestergaard A, Brondum-Nielsen K, Jensen JE, Nielsen JB. {{Patients with rett syndrome sustain low-energy fractures}}. {Pediatr Res};2011 (Apr);69(4):359-364.
We present the first case-control study addressing both fracture occurrence and fracture mechanisms in Rett syndrome (RTT). Two previous studies have shown increased fracture risk in RTT. This was also our hypothesis regarding the Danish RTT population. Therefore, we investigated risk factors associated with low-energy trauma and the association to methyl-CpG-binding protein 2 (MECP2) mutations. A total of 61 female patients with RTT and 122 healthy controls matched according to age and pubertal/menopause status were examined by questionnaires, bone biochemical markers in blood, and clinical and x-ray evaluations. National register search on fracture diagnoses was done to obtain complete fracture histories. Our results showed that patients with RTT sustained significantly more low-energy fractures from early age compared with controls, even though overall fracture occurrence apparently was not increased. Low-energy fractures were significantly associated with less mobility and lack of ambulation. Associations with MECP2 mutations or epilepsy were not demonstrated, contrary to previous findings. Blood biochemistry indicated a possible need for D vitamin supplementation in RTT. Our study casts light on fracture occurrence in RTT and points to a need for future research in bone development and fracture risk to establish directions for improved prevention and treatment of low-energy fractures in RTT. ABBREVIATIONS::
30. Ronald A, Hoekstra RA. {{Autism spectrum disorders and autistic traits: A decade of new twin studies}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Apr);156(3):255-274.
Researchers continue to pursue a better understanding of the symptoms, comorbidities, and causes of autism spectrum disorders. In this article we review more than 30 twin studies of autism spectrum disorders (ASDs) and autistic traits published in the last decade that have contributed to this endeavor. These twin studies have reported on the heritability of autism spectrum disorders and autistic traits in different populations and using different measurement and age groups. These studies have also stimulated debate and new hypotheses regarding why ASDs show substantial symptom heterogeneity, and what causes their comorbidity with intellectual disability, language delay, and other psychiatric disorders such as ADHD. These studies also reveal that the etiology of autism and autistic traits assessed in the general population is more similar than different, which contributes to the question of where the boundary lies between autism and typical development. Recent findings regarding molecular genetic and environmental causes of autism are discussed in the relation to these twin studies. Lastly, methodological assumptions of the twin design are given consideration, as well as issues of measurement. Future research directions are suggested to ensure that this decade is as productive as the last in attempting to disentangle the causes of autism spectrum disorders. (c) 2011 Wiley-Liss, Inc.
31. Rutter ML. {{Progress in understanding autism: 2007-2010}}. {J Autism Dev Disord};2011 (Apr);41(4):395-404.
Scientific progress is discussed in relation to clinical issues; genetic issues; environmental issues; and the state of play on psychological treatments. It is concluded that substantial gains in knowledge have been achieved during the last 3 years, and there have been some unexpected findings, but major puzzles remain. We should be hopeful of ever greater gains in the years ahead, but both prevention and cure remain elusive.
32. Sheth BR, Liu J, Olagbaju O, Varghese L, Mansour R, Reddoch S, Pearson DA, Loveland KA. {{Detecting social and non-social changes in natural scenes: performance of children with and without autism spectrum disorders and typical adults}}. {J Autism Dev Disord};2011 (Apr);41(4):434-446.
We probed differences in the ability to detect and interpret social cues in adults and in children and young adolescents with and without autism spectrum disorders (ASD) by investigating the effect of various social and non-social contexts on the visual exploration of pictures of natural scenes. Children and adolescents relied more on social referencing cues in the scene as compared to adults, and in the presence of such cues, were less able to use other kinds of cues. Typically developing children and adolescents were no better than those with ASD at detecting changes within the various social contexts. Results suggest children and adolescents with ASD use relevant social cues while searching a scene just as typical children do.
33. Shriberg LD, Paul R, Black LM, van Santen JP. {{The hypothesis of apraxia of speech in children with autism spectrum disorder}}. {J Autism Dev Disord};2011 (Apr);41(4):405-426.
In a sample of 46 children aged 4-7 years with Autism Spectrum Disorder (ASD) and intelligible speech, there was no statistical support for the hypothesis of concomitant Childhood Apraxia of Speech (CAS). Perceptual and acoustic measures of participants’ speech, prosody, and voice were compared with data from 40 typically-developing children, 13 preschool children with Speech Delay, and 15 participants aged 5-49 years with CAS in neurogenetic disorders. Speech Delay and Speech Errors, respectively, were modestly and substantially more prevalent in participants with ASD than reported population estimates. Double dissociations in speech, prosody, and voice impairments in ASD were interpreted as consistent with a speech attunement framework, rather than with the motor speech impairments that define CAS.
34. Smith LM. {{« Lessons Learned from Autism: A Parent’s Perspective »}}. {Curr Probl Pediatr Adolesc Health Care};2011 (Apr);41(4):117-118.
35. Tang B, Piazza CC, Dolezal D, Stein MT. {{Severe feeding disorder and malnutrition in 2 children with autism}}. {J Dev Behav Pediatr};2011 (Apr);32(3):264-267.
Leanna, a 10-year-old girl with autism, was hospitalized for severe malnutrition and 20 pound weight loss secondary to reduced intake over 4 months. Her food choices became increasingly restrictive to the point where she only ate certain types and brands of foods. She gradually stopped drinking and developed severe constipation and encopresis. A new behavior of collecting saliva in her mouth and spitting onto napkins also emerged.Vital signs and electrolytes were normal on admission. A nasogastric tube was placed because she refused to eat. A behavior modification plan was implemented that awarded points for completing specific tasks related to feeding, which could later be redeemed for specific rewards, such as computer time. Although her ideal body weight increased from 68% to 75% (due to continuous nasogastric tube feeds), her refusal to eat persisted.Upon further data gathering, the staff learned that she moved and changed schools 5 months ago. She was cared for by either a family friend or paid caregiver while her mother worked. Although she could conduct basic self-care activities without assistance and write and draw at a third-grade level, she functioned cognitively at a 4-year-old level. The behavior plan was modified, breaking the tasks into shorter components with immediate and tangible rewards. She soon began eating small portions of food and spitting less frequently. Toileting was later incorporated into this plan. She was referred to a behavioral therapist in the community to work with her at home and school. Weekly visits with her pediatrician and appointments with a child psychiatrist and dietician were made.Orlando, a 3-year-old boy with autism, was evaluated in the emergency room for lethargy and generalized edema for 6 weeks. The history revealed a restrictive diet of commercial pureed fruit and coconut juice for 2 years. He only ate a particular brand and with specific containers; the limited food intake occurred only with his favorite blanket. He refused to eat other types of food. Outpatient treatments were unsuccessful.On physical examination, he was irritable with an erythematous, scaly rash throughout his body. His hair was thin, coarse, and blonde. He had nonpitting edema in his arms, legs, and periorbital region. The laboratory evaluation was significant for anemia, hypoalbuminemia, and hypoproteinemia.He was admitted to the pediatric service where nutritional formula feedings were initiated through a nasogastric tube. Weight gain was adequate, and the hemoglobin, serum albumen, and protein became normal. The rash improved with zinc supplementation. He was transferred to an inpatient feeding disorders unit where a team of occupational therapists implemented a behavioral modification program to overcome his severe food aversion.
36. Tasdemiroglu E, Kaya M, Yildirim CH, Firat L. {{Response letter to editor: cerebellar mutism and autistic spectrum disorder}}. {Childs Nerv Syst};2011 (Apr);27(4):515.
37. Vanvuchelen M, Roeyers H, De Weerdt W. {{Imitation assessment and its utility to the diagnosis of autism: evidence from consecutive clinical preschool referrals for suspected autism}}. {J Autism Dev Disord};2011 (Apr);41(4):484-496.
The present study sought to examine imitation difficulties as a risk factor for autism. Imitation aptitude was examined in 86 preschoolers suspected of autism (1.9-4.5 years) using the Preschool Imitation and Praxis Scale (PIPS). Differences between imitation, language, motor age-equivalents and nonverbal mental age were used to predict the diagnosis of autism. Multidisciplinary team diagnoses and ADOS-G classifications were used to differentiate children with autism spectrum disorders and non-spectrum developmental disorders. Two factors were found to be significantly associated with autism using simple logistic regression analyses: procedural imitation delay and receptive language delay. In a multivariable setting, only procedural imitation delay remained a significant predictor of autism. Results are new to the literature and require replications.
38. Veenstra-Vanderweele J, Warren Z. {{Social communication deficits in the general population: how far out does the autism spectrum go?}}. {J Am Acad Child Adolesc Psychiatry};2011 (Apr);50(4):326-328.
39. Vladeanu M, Monteith-Hodge EM, Bourne VJ. {{Strength of lateralisation for processing facial emotion in relation to autistic traits in individuals without autism}}. {Laterality};2011 (Mar 28):1-15.
A great number of studies have shown that non-clinical individuals rely predominantly on the right hemisphere to process facial emotion. Previous studies have shown that males suffering from Asperger’s syndrome show a typical right hemisphere bias for processing facial emotion (happiness and sadness) but a reduced right hemisphere bias for processing facial identity. This study looks at the lateralisation of all six basic emotions using the chimeric faces test in 64 non-clinical participants (32 males, 32 females) and correlates it with their autistic traits measured using the Broad Autistic Phenotype Questionnaire. For males only, regression analyses showed a relationship between the aloof personality trait and lateralisation for fear, happiness, and surprise. Males with high autistic scores on the aloof personality subscale (showing a lack of interest in social interaction) were more strongly lateralised to the right hemisphere for processing fear, happiness, and surprise. For males there was no relationship with anger, disgust, sadness, or non-facial stimuli, and for females there were no significant relationships at all. The autistic traits of rigidity and pragmatic language were not significant predictors of emotion lateralisation. The over-reliance on the right hemisphere for processing facial emotion in males seems to support the idea that the autistic brain could be seen as hyper-masculinised, possibly due to prenatal testosterone exposure.
40. Vorstman JA, van Daalen E, Jalali GR, Schmidt ER, Pasterkamp RJ, de Jonge M, Hennekam EA, Janson E, Staal WG, van der Zwaag B, Burbach JP, Kahn RS, Emanuel BS, van Engeland H, Ophoff RA. {{A double hit implicates DIAPH3 as an autism risk gene}}. {Mol Psychiatry};2011 (Apr);16(4):442-451.
Recent studies have shown that more than 10% of autism cases are caused by de novo structural genomic rearrangements. Given that some heritable copy number variants (CNVs) have been observed in patients as well as in healthy controls, to date little attention has been paid to the potential function of these non-de novo CNVs in causing autism. A normally intelligent patient with autism, with non-affected parents, was identified with a maternally inherited 10 Mb deletion at 13q21.2. Sequencing of the genes within the deletion identified a paternally inherited nonsynonymous amino-acid substitution at position 614 of diaphanous homolog 3 (DIAPH3) (proline to threonine; Pro614Thr). This variant, present in a highly conserved domain, was not found in 328 healthy subjects. Experiments showed a transient expression of Diaph3 in the developing murine cerebral cortex, indicating it has a function in brain development. Transfection of Pro614Thr in murine fibroblasts showed a significant reduction in the number of induced filopodia in comparison to the wild-type gene. DIAPH3 is involved in cell migration, axon guidance and neuritogenesis, and is suggested to function downstream of SHANK3. Our findings strongly suggest DIAPH3 as a novel autism susceptibility gene. Moreover, this report of a ‘double-hit’ compound heterozygote for a large, maternally inherited, genomic deletion and a paternally inherited rare missense mutation shows that not only de novo genomic variants in patients should be taken seriously in further study but that inherited CNVs may also provide valuable information.
41. Weinstein M, Ben-Sira L, Levy Y, Zachor DA, Itzhak EB, Artzi M, Tarrasch R, Eksteine PM, Hendler T, Bashat DB. {{Abnormal white matter integrity in young children with autism}}. {Hum Brain Mapp};2011 (Apr);32(4):534-543.
This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism. Hum Brain Mapp, 2011. (c) 2010 Wiley-Liss, Inc.
42. Yang HH, Savostyanov AN, Tsai AC, Liou M. {{Face recognition in Asperger syndrome: A study on EEG spectral power changes}}. {Neurosci Lett};2011 (Apr 1);492(2):84-88.
EEG reactions in emotional face recognition were studied in five participants with Asperger syndrome (AS) and seven control subjects. Control subjects showed a spectral power increase following the stimulus onset in two time-frequency intervals-(1) 150-300ms in the 1-16Hz frequency range and (2) 300-650ms in the 1-8Hz range. Also, alpha/beta desynchronization occurred 400-1000ms after the stimulus onset with maximal amplitude in the posterior region. Theta synchronization (4-8Hz) was weaker in the AS group than in the control group, but beta2 desynchronization was stronger in the AS group. The results were interpreted in terms of automatic and voluntary control of perception.
