1. Aldridge FJ, Gibbs VM, Schmidhofer K, Williams M. {{Investigating the Clinical Usefulness of the Social Responsiveness Scale (SRS) in a Tertiary Level, Autism Spectrum Disorder Specific Assessment Clinic}}. {J Autism Dev Disord};2011 (Apr 23)

The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome for children referred to a tertiary level, autism specific assessment service. Forty eight children (mean age = 8.10; 92% male) underwent a comprehensive ASD assessment. Parent and teacher SRS scores were subsequently compared with diagnostic outcome. Sensitivity was high (91% for parent report; 84% for teacher report), however specificity was much lower (8% for parent report; 41% for teacher report). Results demonstrate a need for caution when interpreting SRS results based on current cut-off scores, particularly in children with previously identified social developmental problems.

2. El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY. {{Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia}}. {Lipids Health Dis};2011 (Apr 22);10(1):63.

ABSTRACT: Backgrounds: Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to compare the relative concentrations of essential fatty acids (Linoleic and alpha- linolenic), their long chain polyunsaturated fatty acids and phospholipids in plasma of autistic patients from Saudi Arabia with age-matching controls. METHODS: 25 autistic children aged 3-15 years and 16 healthy children as control group were included in this study. Relative concentration of essential fatty acids / long chain polyunsaturated fatty acids and omega-3/omega-6 fatty acid series together with phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine were measured in plasma of both groups. RESULTS: Remarkable alteration of essential fatty acids / long chain polyunsaturated fatty acids, omeg-3/ omega-6 and significant lower levels of phospholipids were reported. Reciever Operating characteristics (ROC) analysis of the measured parameters revealed a satisfactory level of sensitivity and specificity. CONCLUSION: Essential fatty acids / long chain polyunsaturated fatty acids and omeg-3/omega-6 ratios, phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine could be used as potential biomarkers that point to specific mechanisms in the development of autism and may help tailor treatment or prevention strategies.

3. Estigarribia B, Martin GE, Roberts JE, Spencer A, Gucwa A, Sideris J. {{Narrative Skill in Boys with Fragile X Syndrome with and without Autism Spectrum Disorder}}. {Appl Psycholinguist};2011;32(2):359-388.

We examined recalled narratives of boys with fragile X syndrome with autism spectrum disorder (FXS-ASD; N=28) and without ASD (FXS-O; N=29), and compared them to those of boys with Down syndrome (DS; N=33) and typically developing boys (TD; N=39). Narratives were scored for mentions of macrostructural Story Grammar elements (Introduction, Relationship, Initiating Events, Internal Response, Attempts/Actions, and Ending). We found that narrative recall is predicted by short-term memory and nonverbal mental age levels in almost all groups (except TD), but not by expressive syntax or caregiver education. After adjusting for these covariates, there were no differences between the three groups with intellectual disability (ID). The FXS-ASD group, however, had significantly poorer performance than the TD group on the overall Story Grammar score, and both the FXS-O and FXS-ASD groups had lower Attempts/Actions scores than the TD group. We conclude that some form of narrative impairment may be associated with FXS, that this impairment may be shared by other forms of ID, and that the presence of ASD has a significantly detrimental effect on narrative recall.

4. Grodberg D, Weinger PM, Kolevzon A, Soorya L, Buxbaum JD. {{Brief Report: The Autism Mental Status Examination: Development of a Brief Autism-Focused Exam}}. {J Autism Dev Disord};2011 (Apr 26)

The Autism Mental Status Examination (AMSE) described here is an eight-item observational assessment that prompts the observation and recording of signs and symptoms of autism spectrum disorders (ASD). The AMSE is intended to take place seamlessly in the context of a clinical exam and produces a total score. Subjects were independently administered the AMSE and the Autism Diagnostic Observation Schedule (ADOS). The ADOS was used to estimate the most effective criterion cut-off on the AMSE. A score of five or greater produced excellent sensitivity and good specificity in a high-risk sample. Internal consistency was acceptable and inter-rater reliability was good to excellent. Preliminary findings indicate excellent classification accuracy and suggest that the AMSE provides a rapid and reliable observational assessment in a high-risk population.

5. Hutman T, Chela MK, Gillespie-Lynch K, Sigman M. {{Selective Visual Attention at Twelve Months: Signs of Autism in Early Social Interactions}}. {J Autism Dev Disord};2011 (Apr 26)

We examined social attention and attention shifting during (a) a play interaction between 12-month olds and an examiner and (b) after the examiner pretended to hurt herself. We coded the target and duration of infants’ visual fixations and frequency of attention shifts. Siblings of children with autism and controls with no family history of autism were tested at 12 months and screened for ASD at 36 months. Groups did not differ on proportion of attention to social stimuli or attention shifting during the play condition. All groups demonstrated more social attention and attention shifting during the distress condition. Infants later diagnosed with ASD tended to continue looking at a toy during the distress condition despite the salience of social information.

6. Lioy DT, Wu WW, Bissonnette JM. {{Autonomic dysfunction with mutations in the gene that encodes methyl-CpG-binding protein 2: Insights into Rett syndrome}}. {Auton Neurosci};2011 (Apr 26);161(1-2):55-62.

Rett syndrome (RTT) is an autism spectrum disorder with an incidence of ~1:10,000 females (reviewed in Bird, 2008; Chahrour et al., 2007; Francke, 2006). Affected individuals are apparently normal at birth. Between 6-18months of age, however, RTT patients begin to exhibit deceleration of head growth, replacement of purposeful hand movements with stereotypic hand wringing, loss of speech, social withdrawal and other autistic features. RTT is caused by loss of function mutations in the gene that encodes methyl-CpG-binding protein 2 (Mecp2) (Amir et al., 1999), a transcriptional repressor that targets genes essential for neuronal survival, dendritic growth, synaptogenesis, and activity dependent plasticity. MECP2 is X-linked, and males die soon after birth. Included in the RTT phenotype are cardiorespiratory disorders involving the autonomic nervous system. The respiratory disorders, including the roles of bioaminergic and brain derived neurotrophic factor (BDNF) signaling in the respiratory pathophysiology of RTT have been recently reviewed (Bissonnette et al., 2007a; Ogier et al., 2008; Katz et al., 2009). Here we will cover the work on RTT regarding respiration that has appeared since 2009 as well as cardiovascular abnormalities.

7. Liu Y, Cherkassky VL, Minshew NJ, Just MA. {{Autonomy of lower-level perception from global processing in autism: Evidence from brain activation and functional connectivity}}. {Neuropsychologia};2011 (Apr 13)

Previous behavioral studies have shown that individuals with autism are less hindered by interference from global processing during the performance of lower-level perceptual tasks, such as finding embedded figures. The primary goal of this study was to examine the brain manifestation of such atypicality in high-functioning autism using fMRI. Fifteen participants with high-functioning autism and fifteen age- and IQ-matched typical controls were asked to perform a lower-level perceptual line-counting task in the presence of a distracting depiction of a 3-D object, in which participants counted whether there were more red or more green contours (In a contrasting 3-D task, participants judged whether the same 3-D stimulus objects (but without color in any contours) depicted a possible or impossible 3-D object). We hypothesized that individuals with autism would be less likely than controls to process the global 3-D information (and would hence show fewer neural signs of such interfering 3-D processing) during the lower-level line-counting task. The fMRI results revealed that in the line-counting task, the autism group did not show the increased medial frontal activity (relative to the possibility task), or the increased functional connectivity between the medial frontal region and posterior visual-spatial regions, demonstrated by the control group. Both findings are indices of lesser effort and difficulty in the line-counting task for the autism group than for the control group, attributed to less interference from the 3-D processing in the autism group. In addition, in the line-counting task, the control group showed a positive correlation between a measure of spatial ability (Vandenberg scores) and activation in the medial frontal region, suggesting that more spatially able control participants did more suppression of the irrelevant 3-D background information in order to focus on the line-counting task. The findings collectively indicate that the global 3-D structure of the figure had a smaller effect, if any, on local processing in the group with autism compared to the control group. The results from this study provide the first direct neural evidence of reduced global-to-local interference in autism.

8. Lugnegard T, Hallerback MU, Gillberg C. {{Psychiatric comorbidity in young adults with a clinical diagnosis of Asperger syndrome}}. {Res Dev Disabil};2011 (Apr 23)

In children with autism spectrum disorders, previous studies have shown high rates of psychiatric comorbidity. To date, studies on adults have been scarce. The aim of the present study was to investigate psychiatric comorbidity in young adults with Asperger syndrome. Participants were 26 men and 28 women (mean age 27 years) with a clinical diagnosis of Asperger syndrome. Psychiatric comorbidity was assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders. IQ was measured using the Wechsler Adult Intelligence Scale, Third Edition. Autism spectrum diagnoses were confirmed using the DIagnostic Interview for Social and Communication Disorders. In our study group, 70% had experienced at least one episode of major depression, and 50% had suffered from recurrent depressive episodes. Anxiety disorders were seen in about 50%. Psychotic disorders and substance-induced disorders were uncommon. In conclusion, young adults with autism spectrum disorders are at high risk for mood and anxiety disorders. To identify these conditions and offer treatment, elevated vigilance is needed in clinical practice.

9. Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG, Fussell JJ, Bellando J, Pavliv O, Rose S, Seidel L, Gaylor DW, Jill James S. {{Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism}}. {J Autism Dev Disord};2011 (Apr 26)

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism.

10. Mostafa GA, Al-Ayadhi LY. {{Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity}}. {J Neuroinflammation};2011 (Apr 25);8(1):39.

ABSTRACT: BACKGROUND: Autoimmunity to the central nervous system (CNS) may play a pathogenic role in a subgroup of patients with autism. This study aimed to investigate the frequency of serum anti-ganglioside M1 auto-antibodies, as indicators of the presence of autoimmunity to CNS, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism. METHODS: Serum anti-ganglioside M1 antibodies were measured, by ELISA, in 54 autistic children, aged between 4 and 12 years, in comparison to 54 healthy-matched children. Autistic severity was assessed by using the Childhood Autism Rating Scale (CARS). RESULTS: Autistic children had significantly higher serum levels of anti-ganglioside M1 antibodies than healthy children (P<0.001). The seropositivity of anti-ganglioside M1 antibodies was found in 74% (40/54) of autistic children. Serum levels of anti-ganglioside M1 antibodies were significantly higher in autistic children with severe autism (63%) than those with mild to moderate autism (37%), P=0.001. Moreover, serum anti-ganglioside M1 antibodies had significant positive correlations with CARS (P<0.001). CONCLUSIONS: Serum levels of anti-ganglioside M1 antibodies were increased in many autistic children. Also, their levels had significant positive correlations with the degree of the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the possible etiopathogenic role of anti-ganglioside M1 auto-antibodies in autism. The role of immunotherapy in autistic patients who have increased serum levels of anti-ganglioside M1 antibodies should also be studied.

11. Schumann G, Coin LJ, Lourdusamy A, Charoen P, Berger KH, Stacey D, Desrivieres S, Aliev FA, Khan AA, Amin N, Aulchenko YS, Bakalkin G, Bakker SJ, Balkau B, Beulens JW, Bilbao A, de Boer RA, Beury D, Bots ML, Breetvelt EJ, Cauchi S, Cavalcanti-Proenca C, Chambers JC, Clarke TK, Dahmen N, de Geus EJ, Dick D, Ducci F, Easton A, Edenberg HJ, Esk T, Fernandez-Medarde A, Foroud T, Freimer NB, Girault JA, Grobbee DE, Guarrera S, Gudbjartsson DF, Hartikainen AL, Heath AC, Hesselbrock V, Hofman A, Hottenga JJ, Isohanni MK, Kaprio J, Khaw KT, Kuehnel B, Laitinen J, Lobbens S, Luan J, Mangino M, Maroteaux M, Matullo G, McCarthy MI, Mueller C, Navis G, Numans ME, Nunez A, Nyholt DR, Onland-Moret CN, Oostra BA, O’Reilly PF, Palkovits M, Penninx BW, Polidoro S, Pouta A, Prokopenko I, Ricceri F, Santos E, Smit JH, Soranzo N, Song K, Sovio U, Stumvoll M, Surakk I, Thorgeirsson TE, Thorsteinsdottir U, Troakes C, Tyrfingsson T, Tonjes A, Uiterwaal CS, Uitterlinden AG, van der Harst P, van der Schouw YT, Staehlin O, Vogelzangs N, Vollenweider P, Waeber G, Wareham NJ, Waterworth DM, Whitfield JB, Wichmann EH, Willemsen G, Witteman JC, Yuan X, Zhai G, Zhao JH, Zhang W, Martin NG, Metspalu A, Doering A, Scott J, Spector TD, Loos RJ, Boomsma DI, Mooser V, Peltonen L, Stefansson K, van Duijn CM, Vineis P, Sommer WH, Kooner JS, Spanagel R, Heberlein UA, Jarvelin MR, Elliott P. {{Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption}}. {Proc Natl Acad Sci U S A};2011 (Apr 26);108(17):7119-7124.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

12. Warren ZE, Foss-Feig JH, Malesa EE, Lee EB, Taylor JL, Newsom CR, Crittendon J, Stone WL. {{Neurocognitive and Behavioral Outcomes of Younger Siblings of Children with Autism Spectrum Disorder at Age Five}}. {J Autism Dev Disord};2011 (Apr 26)

Later-born siblings of children with Autism Spectrum Disorders (ASD) are at increased risk for ASD as well as qualitatively similar traits not meeting clinical cutoffs for the disorder. This study examined age five neurocognitive and behavioral outcomes of 39 younger siblings of children with ASD (Sibs-ASD) and 22 younger siblings of typically developing children (Sibs-TD) previously assessed in a longitudinal investigation starting in the second year of life. There were few group differences between Sibs-TD and Sibs-ASD on global measures of IQ, language, or behavior problems. Sibs-ASD did show vulnerabilities on measures of executive functioning, social cognition, and repetitive behaviors. These results highlight the importance of following sibling risk groups over an extended time period and employing measures targeting broader aspects of development.

13. Weidenheim KM, Escobar A, Rapin I. {{Brief Report: Life History and Neuropathology of a Gifted Man with Asperger Syndrome}}. {J Autism Dev Disord};2011 (Apr 23)

Despite recent interest in the pathogenesis of the autism spectrum disorders (pervasive developmental disorders), neuropathological descriptions of brains of individuals with well documented clinical information and without potentially confounding symptomatology are exceptionally rare. Asperger syndrome differs from classic autism by lack of cognitive impairment or delay in expressive language acquisition. We examined the 1,570 g brain of a 63 year old otherwise healthy mathematician with an Autistic Spectrum Disorder of Asperger subtype. Except for an atypical gyral pattern and megalencephaly, we detected no specific neuropathologic abnormality. Taken together, the behavioral data and pathological findings in this case are compatible with an early neurodevelopmental process affecting multiple neuroanatomic networks, but without a convincing morphologic signature detectable with routine neuropathologic technology.

14. Wills S, Rossi CC, Bennett J, Martinez-Cerdeno V, Ashwood P, Amaral DG, Van de Water J. {{Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism}}. {Mol Autism};2011 (Apr 26);2(1):5.

ABSTRACT: BACKGROUND: Autism is a neurodevelopmental disorder characterized by impairments in social interaction, deficits in verbal and nonverbal communication, with the presence of repetitive behaviors or a limited repertoire of activities and interests. The causes for autism are currently unclear. In a previous study, we determined that 21% of children with autism had plasma autoantibodies that were immunoreactive with a population of neurons in the cerebellum that appeared to be Golgi cells, a GABAergic interneuron. METHODS: We have now extended this analysis by examining plasma immunoreactivity in the remainder of the brain. To determine cell specificity, double labeling studies, that included one of the calcium binding proteins that are commonly co-localized in GABAergic neurons (calbindin, paralbumin, or calretinin), were also carried out to determine which GABAergic neurons were immunoreactive. Coronal sections through the rostrocaudal extent of the macaque monkey brain were reacted with plasma from each of seven subjects with autism who had previously demonstrated positive Golgi cell staining, as well as six negative controls. In addition, brain sections from murine adult males were similarly examined. RESULTS: In each case, specific staining was observed for neurons that had the morphological appearance of interneurons. By double labeling sections with plasma and with antibodies directed against gamma-aminobutyric acid (GABA), we determined that all autoantibody-positive neurons were GABAergic. However, not all GABAergic neurons were autoantibody-positive. Calbindin was co-labeled in several of the autoantibody labeled cells while parvalbumin co-labeling was less frequently observed. Autoantibody-positive cells rarely expressed calretinin. Sections from the mouse brain processed similarly to the primate sections also demonstrated immunoreactivity to interneurons distributed throughout the neocortex and many subcortical regions. Some cell populations stained in the primate (such as the Golgi neurons in the cerebellum) were not as robustly immunoreactive in the mouse brain. CONCLUSIONS: These results suggest that the earlier report of autoantibody immunoreactivity to specific cells in the cerebellum extend to other regions of the brain. Further, these findings confirm the autoantibody-targeted cells to be a sub-population of GABAergic interneurons. The potential impact of these autoantibodies on GABAergic disruption with respect to the etiology of autism is discussed herein.

15. Zachor D, Yang JW, Ben Itzchak E, Furniss F, Pegg E, Matson JL, Horovitz M, Sipes M, Chung KM, Jung W. {{Cross-cultural differences in comorbid symptoms of children with autism spectrum disorders: An international examination between Israel, South Korea, the United Kingdom and the United States of America}}. {Dev Neurorehabil};2011 (Apr 24)

Objective: To examine the relationship between culture and symptoms of comorbid psychopathology in those with autism spectrum disorders (ASD). Design: Multivariate analyses of variance (MANOVAs) for each country and each sub-scale of the Autism Spectrum Disorders-Comorbid for Children (ASD-CC). Follow-up independent univariate analyses and post-hoc tests as needed. Methods: Separate samples from South Korea, the UK and Israel were compared to a sample from the US in order to examine cultural contributions, using the ASD-CC. Results: Overall, few differences were found. Significantly, the US had significantly higher scores than South Korea on the avoidant sub-scale. Additionally, the US had significantly higher scores than Israel on the over-eating and tantrum sub-scales. No significant differences were found between the US and the UK. Conclusion: Cultural factors, such as views of typical behaviour, should be taken into account when examining symptoms of comorbidity in children with ASD.