1. Allen-Brady K, Cai G, Cannon D, Robison R, McMahon WM, Coon H, Buxbaum JD. {{No evidence for IL1RAPL1 involvement in selected high-risk autism pedigrees from the AGRE data set}}. {Autism Res};2011 (Apr 12)
Finding predisposition genes for Autism Spectrum Disorder (ASD) has proven challenging, and new methods are needed to aid the process. Using pedigree structure as a strategy to identify ASD predisposition genes, we previously performed a genome-wide linkage scan of 86 selected families from the Autism Resource Exchange (AGRE) that appeared to inherit ASD in a dominant manner. We identified a suggestive linkage peak on chromosome Xp22.11-p21.2 that encompasses the IL1RAPL1 gene, a strong candidate gene for ASD. In this follow-up study, we sequenced the coding regions of the IL1RAPL1 gene in 14 male cases representing one case from each pedigree that showed at least nominal linkage evidence on per pedigree basis to the chromosome X region. We observed no deleterious mutations or deletions in the IL1RAPL1 gene in these 14 ASD cases. A SNP was identified in exon 2 in five cases and a variant of unknown significance was identified in intron 6 in a single case. In conclusion, coding changes of the IL1RAPL1 gene do not appear to be associated with ASD in selected AGRE families with linkage evidence to the chromosome Xp22.11-p21.2 region. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
2. Anders TF, Iosif AM, Schwichtenberg AJ, Tang K, Goodlin-Jones BL. {{Six-month sleep-wake organization and stability in preschool-age children with autism, developmental delay, and typical development}}. {Behav Sleep Med};2011 (Apr);9(2):92-106.
This study examined sleep-wake patterns in 3 matched comparison groups of preschool-aged children: children with autism (AUT), children with developmental delay (DD) without AUT, and children who are developing typically (TYP). Sleep was assessed via actigraphy and parent-report diaries for 7 consecutive 24-hr periods across 3 time points: at enrollment (n = 194), 3 months later (n = 179), and 6 months after enrollment (n = 173). At each recording period, children in the AUT group slept less per 24-hr period, on average, and were less likely to awaken at night than children in the other two groups. In contrast, children in the DD group had more frequent and longer duration nighttime awakenings than children in the AUT group. Overall, children in the 2 neurodevelopmentally disordered groups demonstrated more night-to-night variability in their sleep-wake measures than children in the TYP group.
3. Barua M, Jenkins EC, Chen W, Kuizon S, Pullarkat RK, Junaid MA. {{Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity-implications for autism}}. {Autism Res};2011 (Apr 12)
Autism is a pervasive, heterogeneous, neurodevelopmental disability characterized by impairments in verbal communications, reciprocal social interactions, and restricted repetitive stereotyped behaviors. Evidence suggests the involvement of multiple genetic factors in the etiology of autism, and extensive genome-wide association studies have revealed several candidate genes that bear single nucleotide polymorphisms (SNPs) in non-coding and coding regions. We have shown that a non-conservative, non-synonymous SNP in the glyoxalase I gene, GLOI, may be an autism susceptibility factor. The GLOI rs2736654 SNP is a C–>A change that causes an Ala111Glu change in the Glo1 enzyme. To identify the significance of the SNP, we have conducted functional assays for Glo1. We now present evidence that the presence of the A-allele at rs2736654 results in reduced enzyme activity. Glo1 activity is decreased in lymphoblastoid cells that are homozygous for the A allele. The Glu-isoform of Glo1 in these cells is hyperphosphorylated. Direct HPLC measurements of the glyoxalase I substrate, methylglyoxal (MG), show an increase in MG in these cells. Western blot analysis revealed elevated levels of the receptor for advanced glycation end products (RAGEs). We also show that MG is toxic to the developing neuronal cells. We suggest that accumulation of MG results in the formation of AGEs, which induce expression of the RAGE that during crucial neuronal development may be a factor in the pathology of autism. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
4. Booth R, Wallace GL, Happe F. {{Connectivity and the corpus callosum in autism spectrum conditions Insights from comparison of autism and callosal agenesis}}. {Prog Brain Res};2011;189:303-317.
Neural models of autism spectrum disorders (ASDs) have moved, in recent years, from a lesion model to a focus on abnormal connectivity. In this chapter, we review this work and summarize findings from our recent research comparing autism and agenesis of the corpus callosum (AgCC). We discuss our findings in the context of the « fractionable triad » account and highlight three main points. First, the social aspects of autism can be found in isolation, not accompanied by the nonsocial features of this disorder, supporting a view of autism as a « compound, » rather than « monolithic, » condition. Second, many young people with callosal agenesis show theory of mind- and emotion-processing deficits akin to those seen in autism. Diagnostic overshadowing may mean these people do not receive interventions that have proven beneficial in ASD. Last, study of AgCC shows that it is possible, in some cases, to develop good social cognitive skills in the absence of the corpus callosum, presenting a challenge to future connectivity models of autism.
5. Elsabbagh M, Holmboe K, Gliga T, Mercure E, Hudry K, Charman T, Baron-Cohen S, Bolton P, Johnson MH. {{Social and attention factors during infancy and the later emergence of autism characteristics}}. {Prog Brain Res};2011;189C:195-207.
Characteristic features of autism include atypical social perception and social-communication skills, and atypical visual attention, alongside rigid and repetitive thinking and behavior. Debate has focused on whether the later emergence of atypical social skills is a consequence of attention problems early in life, or, conversely, whether early social deficits have knock-on consequences for the later development of attention skills. We investigated this question based on evidence from infants at familial risk for a later diagnosis of autism by virtue of being younger siblings of children with a diagnosis. Around 9months, at-risk siblings differed as a group from controls, both in measures of social perception and inhibitory control. We present preliminary data from an ongoing longitudinal research program, suggesting clear associations between some of these infant measures and autism-related characteristics at 3years. We discuss the findings in terms of the emergent nature of autism as a result of complex developmental interactions among brain networks.
6. Itzchak EB, Lahat E, Zachor DA. {{Advanced parental ages and low birth weight in autism spectrum disorders-Rates and effect on functioning}}. {Res Dev Disabil};2011 (Apr 15)
OBJECTIVES: (1) To assess the distribution of parental age and birth weight in a large cohort with autism spectrum disorder (ASD) and to compare them to Israeli national data. (2) To examine possible relationships between these risk factors and functioning. METHODS: The study included 529 participants diagnosed with ASD using standardized tests: the Autism Diagnosis Interview-Revised and the Autism Diagnosis Observation Schedule (ADOS). Medical, developmental and familial histories (gender, age, pregnancy and birth information, parental ages) were obtained. Autism severity was assessed using the new ADOS severity scale and adaptive skill using the Vineland Adaptive Behavior Scales. RESULTS: Advanced parental age was associated with ASD. In the older age range the percentages of mothers (35-44y) and fathers (30-40y) were significantly higher in the ASD cohort in comparison to the Israeli newborn data. The ASD cohort had significantly higher percentages of low birth weight (<2500g) and very low birth weight (VLBW<1500g) in comparison to the Israeli newborn data. Of these risk factors, only VLBW was associated with lower adaptive functioning. The group with VLBW had lower scores in daily living, socialization and motor skills in comparison to the >1500g group. Autism severity was not associated with advanced parental age or VLBW. CONCLUSIONS: The shift in parental age distribution and birth weight in our ASD cohort suggests that the increase in ASD prevalence in recent years might be associated with novel prenatal insults. An adverse fetal course resulting in VLBW may represent a « second hit » phenomenon, causing a poorer outcome.
7. Qiu S, Anderson CT, Levitt P, Shepherd GM. {{Circuit-specific intracortical hyperconnectivity in mice with deletion of the autism-associated met receptor tyrosine kinase}}. {J Neurosci};2011 (Apr 13);31(15):5855-5864.
Local hyperconnectivity in the neocortex is a hypothesized pathophysiological state in autism spectrum disorder (ASD). MET, a receptor tyrosine kinase that regulates dendrite and spine morphogenesis, has been established as a risk gene for ASD. Here, we analyzed the synaptic circuit organization of identified pyramidal neurons in the anterior frontal cortex of mice with a dorsal pallium-derived, conditional knock-out (cKO) of Met. Synaptic mapping by glutamate uncaging identified layer 2/3 as the main source of local excitatory input to layer 5 projection neurons in controls. In both cKO and heterozygotes, this pathway was stronger by a factor of approximately 2. This increase was both sublayer and projection-class specific, restricted to corticostriatal neurons in upper layer 5B and not neighboring corticopontine neurons. Paired recordings in cKO slices demonstrated increased unitary connectivity. We propose that excitatory hyperconnectivity in specific neocortical microcircuits constitutes a physiological basis for Met-mediated ASD risk.
8. Tallberg T, Dabek J, Hallamaa R, Atroshi F. {{Lipidomics: the function of vital lipids in embryogenesis preventing autism spectrum disorders, treating sterile inflammatory diatheses with a lymphopoietic central nervous system component}}. {J Lipids};2011;2011:137175.
The central role performed by billions of vital central nervous system (CNS) lipids « lipidomics » in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.
9. Tochimoto S, Kurata K, Munesue T. {{‘Time slip’ phenomenon in adolescents and adults with autism spectrum disorders: Case series}}. {Psychiatry Clin Neurosci};2011 (Apr 14)
In recent years, it has been noticed that adolescent and adult patients with autism spectrum disorder (ASD) sometimes visit psychiatric medical institutions. In some cases, these patients commit an act of violence and are dealt with by psychiatric emergency and forensic psychiatric services. In this report, we present two cases with ASD who visited a psychiatric emergency service because of the ‘time slip’ phenomenon, and discuss the clinical significance of this phenomenon.
