1. Adamson LB, Deckner DF, Bakeman R. {{Early Interests and Joint Engagement in Typical Development, Autism, and Down Syndrome}}. {J Autism Dev Disord};2009 (Dec 12)

This study examines how spontaneous interests in people and in objects relate to joint engagement in typically developing toddlers and young children with autism or Down syndrome. Ratings of interests were made repeatedly during intermissions in a laboratory-based protocol focused on caregiver-child interactions. Interests were moderated by diagnosis and relatively stable across intermissions. In autism, interest in people tended to be low and to decline rapidly, and the balance of interests favored familiar objects over people. Lower interest in people and in unfamiliar objects was associated with less coordinated joint engagement and with less steep developmental trajectories for symbol-infused joint engagement. These findings suggest that variations in interests may contribute to differences in the child’s engagement during social interactions that facilitate the acquisition of language.

2. Calahorro F, Alejandre E, Ruiz-Rubio M. {{Osmotic Avoidance in « Caenorhabditis elegans »: Synaptic Function of Two Genes, Orthologues of Human « NRXN1 » and « NLGN1 », as Candidates for Autism}}. {J Vis Exp};2009 (34)

Neurexins and neuroligins are cell adhesion molecules present in excitatory and inhibitory synapses, and they are required for correct neuron network function(1). These proteins are found at the presynaptic and postsynaptic membranes (2). Studies in mice indicate that neurexins and neurologins have an essential role in synaptic transmission (1). Recent reports have shown that altered neuronal connections during the development of the human nervous system could constitute the basis of the etiology of numerous cases of autism spectrum disorders (3). Caenorhabditis elegans could be used as an experimental tool to facilitate the study of the functioning of synaptic components, because of its simplicity for laboratory experimentation, and given that its nervous system and synaptic wiring has been fully characterized. In C. elegans nrx-1 and nlg-1 genes are orthologous to human NRXN1 and NLGN1 genes which encode alpha-neurexin-1 and neuroligin-1 proteins, respectively. In humans and nematodes, the organization of neurexins and neuroligins is similar in respect to functional domains. The head of the nematode contains the amphid, a sensory organ of the nematode, which mediates responses to different stimuli, including osmotic strength. The amphid is made of 12 sensory bipolar neurons with ciliated dendrites and one presynaptic terminal axon (4). Two of these neurons, named ASHR and ASHL are particularly important in osmotic sensory function, detecting water-soluble repellents with high osmotic strength (5). The dendrites of these two neurons lengthen to the tip of the mouth and the axons extend to the nerve ring, where they make synaptic connections with other neurons determining the behavioral response (6). To evaluate the implications of neurexin and neuroligin in high osmotic strength avoidance, we show the different response of C. elegans mutants defective in nrx-1 and nlg-1 genes, using a method based on a 4M fructose ring (7). The behavioral phenotypes were confirmed using specific RNAi clones (8). In C. elegans, the dsRNA required to trigger RNAi can be administered by feeding (9). The delivery of dsRNA through food induces the RNAi interference of the gene of interest thus allowing the identification of genetic components and network pathways.

3. Crepel A, Breckpot J, Fryns JP, De la Marche W, Steyaert J, Devriendt K, Peeters H. {{DISC1 duplication in two brothers with autism and mild mental retardation}}. {Clin Genet};2009 (Dec 10)

We describe the identification and delineation of an inherited 2.07 Mb microduplication in 1q42.2 in two brothers with autism and mild mental retardation. Since this duplication was not present in 1577 Belgian persons, we consider this as an extremely rare variant which has the potential to provide further insight into the genetics of autism. The duplication contains seven genes including the DISC1 gene, an interesting candidate gene that has been associated to schizophrenia, bipolar disorder, autism and Asperger syndrome. In this report we describe additional analyses undertaken to investigate the causal relationship of the duplication to the autism phenotype. We conclude that the 1q42.2 microduplication probably confers susceptibility to autism in the current family. This study is a typical illustration of the difficult interpretation of causality of a very rare variant in neuropsychiatric disease and the challenge of genetic counselling in a particular family.

4. Devincent CJ, Gadow KD. {{Relative clinical utility of three child symptom inventory-4 scoring algorithms for differentiating children with autism spectrum disorder vs. attention-deficit hyperactivity disorder}}. {Autism Res};2009 (Dec 11)

Objective: The present study compared three separate Child Symptom Inventory-4 (CSI-4) scoring algorithms for differentiating children with autism spectrum disorder (ASD) from youngsters with attention-deficit/hyperactivity disorder (ADHD). Method: Parents/teachers completed the CSI-4, a DSM-IV-referenced rating scale, for 6 to 12-year-old clinical referrals with ASD (N=186) and ADHD (N=251). Algorithms were based on either all CSI-4 items (forward logistic regressions) or the 12 DSM-IV symptoms of pervasive developmental disorder (PDD) included in the CSI-4. Results: ROC analyses indicated generally good to excellent values for area under the curve, sensitivity, specificity, and positive predictive power. Algorithms for parent ratings were superior to teacher ratings. The algorithm based solely on PDD symptoms evidenced the greatest generalizability. Conclusion: Although algorithms generated from regression analyses produced greater clinical utility for specific samples, the PDD-based algorithm resulted in greater stability across samples.

5. Hobson RP, Lee A, Hobson JA. {{Personal Pronouns and Communicative Engagement in Autism}}. {J Autism Dev Disord};2009 (Dec 15)

In three experimental conditions, we tested matched children with and without autism (n = 15 per group) for their comprehension and use of first person plural (‘we’) and third person singular (‘he’) pronouns, and examined whether such linguistic functioning related to their social interaction. The groups were indistinguishable in their comprehension and use of ‘we’ pronouns, although within each group, such usage was correlated with ratings of interpersonal connectedness with the collaborator. On the other hand, participants with autism were less likely to use third person pronouns or to show patterns of eye gaze reflecting engagement with an interlocutor’s stance vis-a-vis a third person. In these settings, atypical third person pronoun usage seemed to reflect limited communicative engagement, but first person pronouns were relatively spared.

6. Hollander E, Chaplin W, Soorya L, Wasserman S, Novotny S, Rusoff J, Feirsen N, Pepa L, Anagnostou E. {{Divalproex Sodium vs Placebo for the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorders}}. {Neuropsychopharmacology};2009 (Dec 9)

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests. Irritability/aggression is a significant comorbid symptom in this population, which greatly impacts burden of care. This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD. This was a 12-week randomized, double-blind, placebo-controlled trial. All efficacy measures were obtained by an independent evaluator blinded to randomization condition and side effects. A total of 55 subjects gavetheir consent and 27 were randomized in a 1 : 1 manner (mean age 9.46+/-2.46, mean nonverbal IQ 63.3+/-23.9). Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects (increased irritability). Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement, which focused on irritability. Overall, 62.5% of divalproex subjects vs 9% of placebo subjects were responders (CGI-irritability OR: 16.7, Fisher’s exact p=0.008). A statistically significant improvement was also noted on the ABC-Irritability subscale (p=0.048). There was a trend for responders to have higher valproate blood levels compared with nonresponders. This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD. Larger sample follow-up studies are warranted.Neuropsychopharmacology advance online publication, 9 December 2009; doi:10.1038/npp.2009.202.

7. Kehat R, Bonsall DJ. {{Recurrent corneal metallic foreign bodies in children with autism spectrum disorders}}. {J Aapos};2009 (Dec);13(6):621-622.

Corneal metallic foreign body is a common condition in working-age adults due to occupational exposure, such as grinding, welding, and hammering. Ocular trauma is a leading cause of vision loss in children; however, corneal metallic foreign bodies are rare in the pediatric population. Here we describe 2 children suffering from autism spectrum disorders presenting with recurrent corneal metallic foreign bodies. Meticulous history revealed that both children extensively used a therapeutic home swing with metallic suspensions, suggesting the potential mechanism for the recurrent corneal metallic foreign bodies. Furthermore, the use of protective eyewear during swinging prevented further recurrences. Awareness of this potential danger is particularly important in children with disabilities, who may have difficulty communicating their concerns and cooperating during examination and treatment.

8. Kelemenova S, Ostatnikova D. {{Neuroendocrine pathways altered in autism. Special role of reelin}}. {Neuro Endocrinol Lett};2009 (Oct 11);30(4)

Autism is the most genetically influenced neuropsychiatric disorder with heritabilityof approximately 90%. Since genetic factors seem to play a crucial role inautism etiology, enormous attention is focused on genetic analyses of the disorder.Reelin, one of the autism candidates, is necessary in regulation of neuronalmigration during brain development and also in maintaining synaptic plasticityduring postnatal life period. Reduced reelin levels were observed in sera and braincortices of autistic patients. In this review, abnormalities in reelin signaling andthe relationship between reelin deficiency and principal neuroendocrine pathwaysare discussed.

9. Lombardo MV, Chakrabarti B, Bullmore ET, Sadek SA, Pasco G, Wheelwright SJ, Suckling J, Baron-Cohen S. {{Atypical neural self-representation in autism}}. {Brain};2009 (Dec 13)MRC AIMS Consortium

The ‘self’ is a complex multidimensional construct deeply embedded and in many ways defined by our relations with the social world. Individuals with autism are impaired in both self-referential and other-referential social cognitive processing. Atypical neural representation of the self may be a key to understanding the nature of such impairments. Using functional magnetic resonance imaging we scanned adult males with an autism spectrum condition and age and IQ-matched neurotypical males while they made reflective mentalizing or physical judgements about themselves or the British Queen. Neurotypical individuals preferentially recruit the middle cingulate cortex and ventromedial prefrontal cortex in response to self compared with other-referential processing. In autism, ventromedial prefrontal cortex responded equally to self and other, while middle cingulate cortex responded more to other-mentalizing than self-mentalizing. These atypical responses occur only in areas where self-information is preferentially processed and does not affect areas that preferentially respond to other-referential information. In autism, atypical neural self-representation was also apparent via reduced functional connectivity between ventromedial prefrontal cortex and areas associated with lower level embodied representations, such as ventral premotor and somatosensory cortex. Furthermore, the magnitude of neural self-other distinction in ventromedial prefrontal cortex was strongly related to the magnitude of early childhood social impairments in autism. Individuals whose ventromedial prefrontal cortex made the largest distinction between mentalizing about self and other were least socially impaired in early childhood, while those whose ventromedial prefrontal cortex made little to no distinction between mentalizing about self and other were the most socially impaired in early childhood. These observations reveal that the atypical organization of neural circuitry preferentially coding for self-information is a key mechanism at the heart of both self-referential and social impairments in autism.

10. Malloy C, Yousef E. {{To test or not to test: parent information for discussions of food allergy and autism}}. {Del Med J};2009 (Oct);81(10):357-359.

11. Marschik PB, Einspieler C, Prechtl HF, Oberle A, Laccone F. {{‘Relabelling the preserved speech variant of Rett syndrome?’}} {Dev Med Child Neurol};2009 (Dec 4)

12. Momoi T, Fujita E, Senoo H, Momoi M. {{Genetic factors and epigenetic factors for autism: endoplasmic reticulum stress and impaired synaptic function}}. {Cell Biol Int} (Jan);34(1):13-19.

The molecular pathogenesis of ASD (autism spectrum disorder), one of the heritable neurodevelopmental disorders, is not well understood, although over 15 autistic-susceptible gene loci have been extensively studied. A major issue is whether the proteins that these candidate genes encode are involved in general function and signal transduction. Several mutations in genes encoding synaptic adhesion molecules such as neuroligin, neurexin, CNTNAP (contactin-associated protein) and CADM1 (cell-adhesion molecule 1) found in ASD suggest that impaired synaptic function is the underlying pathogenesis. However, knockout mouse models of these mutations do not show all of the autism-related symptoms, suggesting that gain-of-function in addition to loss-of-function arising from these mutations may be associated with ASD pathogenesis. Another finding is that family members with a given mutation frequently do not manifest autistic symptoms, which possibly may be because of gender effects, dominance theory and environmental factors, including hormones and stress. Thus epigenetic factors complicate our understanding of the relationship between these mutated genes and ASD pathogenesis. We focus in the present review on findings that ER (endoplasmic reticulum) stress arising from these mutations causes a trafficking disorder of synaptic receptors, such as GABA (gamma-aminobutyric acid) B-receptors, and leads to their impaired synaptic function and signal transduction. In the present review we propose a hypothesis that ASD pathogenesis is linked not only to loss-of-function but also to gain-of-function, with an ER stress response to unfolded proteins under the influence of epigenetic factors.

13. Piravej K, Tangtrongchitr P, Chandarasiri P, Paothong L, Sukprasong S. {{Effects of Thai Traditional Massage on Autistic Children’s Behavior}}. {J Altern Complement Med};2009 (Dec);15(12):1355-1361.

Abstract Objectives: The objective of this study was to access whether there were any therapeutic effects of Thai Traditional Massage (TTM) on major behavioral and emotional disturbances in Thai autistic children. Design: This was a randomized controlled trial study. Settings/location: The study was conducted at the Rehabilitation Centre of the Thai Red Cross Society. Subjects: A total of 60 autistic children between the ages of 3 and 10 completed this study. Interventions: Standard sensory integration therapy (SI) was compared to the SI with TTM treatments. Outcome measures: Parents and teachers assessed major behavior disturbances using the Conners’ Rating Scales at 0 and 8 weeks. Sleep Diary (SD), recorded by the parents, assessed the patient’s sleeping patterns every week. Results: Sixty (60) autistic children, mean age 4.67 +/- 1.82, were recruited. No statistical differences were seen in the demographic and baseline data among both groups. From both the Conners’ Teacher Questionnaire and SD, statistical improvement was detected for conduct problem, hyperactivity, inattention-passivity, hyperactivity index, and sleeping behavior. However, results from the Conners’ Parent Questionnaire revealed an improvement only for anxiety (p = 0.04) in the massage group, whereas when both groups were compared, a significant improvement in conduct problem (p = 0.03) and anxiety (p = 0.01) was found. Results indicated that TTM may have a positive effect in improving stereotypical behaviors in autistic children. Conclusions: Over a period of 8 weeks, our findings suggested that TTM could be used as a complementary therapy for autistic children in Thailand.

14. Ronald A, Butcher LM, Docherty S, Davis OS, Schalkwyk LC, Craig IW, Plomin R. A Genome-Wide {{Association Study of Social and Non-Social Autistic-Like Traits in the General Population Using Pooled DNA, 500 K SNP Microarrays and Both Community and Diagnosed Autism Replication Samples}}. {Behav Genet};2009 (Dec 13)

Two separate genome-wide association studies were conducted to identify single nucleotide polymorphisms (SNPs) associated with social and nonsocial autistic-like traits. We predicted that we would find SNPs associated with social and non-social autistic-like traits and that different SNPs would be associated with social and nonsocial. In Stage 1, each study screened for allele frequency differences in ~430,000 autosomal SNPs using pooled DNA on microarrays in high-scoring versus low-scoring boys from a general population sample (N = ~400/group). In Stage 2, 22 and 20 SNPs in the social and non-social studies, respectively, were tested for QTL association by individually genotyping an independent community sample of 1,400 boys. One SNP (rs11894053) was nominally associated (P < .05, uncorrected for multiple testing) with social autistic-like traits. When the sample was increased by adding females, 2 additional SNPs were nominally significant (P < .05). These 3 SNPs, however, showed no significant association in transmission disequilibrium analyses of diagnosed ASD families.

15. Spiroski M, Trajkovski V, Trajkov D, Petlichkovski A, Efinska-Mladenovska O, Hristomanova S, Djulejic E, Paneva M, Bozhikov J. {{Family analysis of immunoglobulin classes and subclasses in children with autistic disorder}}. {Bosn J Basic Med Sci};2009 (Nov);9(4):283-289.

Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

16. Welch TR. {{Longevity in Rett syndrome}}. {J Pediatr} (Jan);156(1):A1-2.

17. Weng SJ, Wiggins JL, Peltier SJ, Carrasco M, Risi S, Lord C, Monk CS. {{Alterations of resting state functional connectivity in the default network in adolescents with autism spectrum disorders}}. {Brain Res};2009 (Dec 11)

Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a cognitive task, but also exists in the absence of a task (i.e., « rest »). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.