1. Carayol J, Sacco R, Tores F, Rousseau F, Lewin P, Hager J, Persico AM. {{Converging Evidence for an Association of ATP2B2 Allelic Variants with Autism in Male Subjects}}. {Biol Psychiatry};2011 (Jul 12)
BACKGROUND: Autism is a severe developmental disorder, with strong genetic underpinnings. Previous genome-wide scans unveiled a linkage region spanning 3.5 Mb, located on human chromosome 3p25. This region encompasses the ATP2B2 gene, encoding the plasma membrane calcium-transporting ATPase 2 (PMCA2), which extrudes calcium (Ca(2+)) from the cytosol into the extracellular space. Multiple lines of evidence support excessive intracellular Ca(2+) signaling in autism spectrum disorder (ASD), making ATP2B2 an attractive candidate gene. METHODS: We performed a family-based association study in an exploratory sample of 277 autism genetic resource exchange families and in a replication sample including 406 families primarily recruited in Italy. RESULTS: Several markers were significantly associated with ASD in the exploratory sample, and the same risk alleles at single nucleotide polymorphisms rs3774180, rs2278556, and rs241509 were found associated with ASD in the replication sample after correction for multiple testing. In both samples, the association was present in male subjects only. Markers associated with autism are all comprised within a single block of strong linkage disequilibrium spanning several exons, and the « risk » allele seems to follow a recessive mode of transmission. CONCLUSIONS: These results provide converging evidence for an association between ATP2B2 gene variants and autism in male subjects, spurring interest into the identification of functional variants, most likely involved in the homeostasis of Ca(2+) signaling. Additional support comes from a recent genome-wide association study by the Autism Genome Project, which highlights the same linkage disequilibrium region of the gene.
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2. Choudhury PR, Lahiri S, Rajamma U. {{Glutamate mediated signaling in the pathophysiology of autism spectrum disorders}}. {Pharmacol Biochem Behav};2011 (Jul 5)
Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder. During fetal and neonatal brain development, the cues for neurodevelopment are regulated in a well orchestrated manner. Generally, neurotransmitters play a major role in the formation of central nervous system (CNS) and peripheral nervous system (PNS). Glutamate, the excitatory neurotransmitter actively participates in various neurodevelopmental processes through complex regulatory events. Excitatory neurotransmitter signaling via glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in ASD. Therefore, glutamate and its regulatory molecules are considered as potential targets for these disorders. Pharmacological, biochemical and behavioral studies reveal possible involvement of glutamatergic system in ASD pathology. An abnormal increase in electrical activity resulting from excessive glutamate signaling causes prolonged alterations in behavior, as commonly seen in ASDs. On the contrary, reports on animal models of hypoglutamatergia demonstrate phenotypes that overlap with features seen in autism. So controversies prevail whether to regard autism as hyper- or hypo-glutamatergic disorder. This paper reviews the role of glutamate and its regulatory proteins such as different receptors, transporters and metabolizing enzymes in the pathophysiology of ASD based on evidences gathered through multidisciplinary approaches. All these information raise the possibility of exploiting glutamatergic neurotransmitter system for future therapeutic interventions for ASD.
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3. Jeong JW, Kumar A, Sundaram SK, Chugani HT, Chugani DC. {{Sharp Curvature of Frontal Lobe White Matter Pathways in Children with Autism Spectrum Disorders: Tract-Based Morphometry Analysis}}. {AJNR Am J Neuroradiol};2011 (Jul 14)
BACKGROUND AND PURPOSE: Because we had previously observed geometric changes of frontal lobe association pathways in children with ASD, in the present study we analyzed the curvature of these white matter pathways by using an objective TBM analysis. MATERIALS AND METHODS: Diffusion tensor imaging was performed in 32 children with ASD and 14 children with typical development. Curvature, FA, AD, and RD of bilateral AF, UF, and gCC were investigated by using the TBM group analysis assessed by P(FDR) for multiple comparisons. RESULTS: Significantly higher curvatures were found in children with ASD, especially at the parietotemporal junction for AF (left, P(FDR) < .001; right, P(FDR) < .01), at the frontotemporal junction for UF (left, P(FDR) < .005; right, P(FDR) < .03), and at the midline of the gCC (P(FDR) < .0001). RD was significantly higher in children with ASD at the same bending regions of AF (left, P(FDR) < .03, right, P(FDR) < .02), UF (left, P(FDR) < .04), and gCC (P(FDR) < .01). CONCLUSIONS: Higher curvature and curvature-dependent RD changes in children with ASD may be the result of higher attenuation of thinner axons in these frontal lobe tracts.
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4. Obrusnikova I, Dillon SR. {{Challenging situations when teaching children with autism spectrum disorders in general physical education}}. {Adapt Phys Activ Q};2011 (Apr);28(2):113-131.
As the first step of an instrument development, teaching challenges that occur when students with autism spectrum disorders are educated in general physical education were elicited using Goldfried and D’Zurilla’s (1969) behavioral-analytic model. Data were collected from a convenience sample of 43 certified physical educators (29 women and 14 men) using a demographic questionnaire and an elicitation questionnaire. Participants listed 225 teaching challenges, 46% related to cooperative, 31% to competitive, and 24% to individualistic learning situations. Teaching challenges were categorized into nine themes: inattentive and hyperactive behaviors, social impairment, emotional regulation difficulties, difficulties understanding and performing tasks, narrow focus and inflexible adherence to routines and structure, isolation by classmates, negative effects on classmates’ learning, and need for support.
5. Schiff M, Benoist JF, Aissaoui S, Boepsflug-Tanguy O, Mouren MC, de Baulny HO, Delorme R. {{Should metabolic diseases be systematically screened in nonsyndromic autism spectrum disorders?}}. {PLoS One};2011;6(7):e21932.
BACKGROUND: In the investigation of autism spectrum disorders (ASD), a genetic cause is found in approximately 10-20%. Among these cases, the prevalence of the rare inherited metabolic disorders (IMD) is unknown and poorly evaluated. An IMD responsible for ASD is usually identified by the associated clinical phenotype such as dysmorphic features, ataxia, microcephaly, epilepsy, and severe intellectual disability (ID). In rare cases, however, ASD may be considered as nonsyndromic at the onset of a related IMD. OBJECTIVES: To evaluate the utility of routine metabolic investigations in nonsyndromic ASD. PATIENTS AND METHODS: We retrospectively analyzed the results of a metabolic workup (urinary mucopolysaccharides, urinary purines and pyrimidines, urinary creatine and guanidinoacetate, urinary organic acids, plasma and urinary amino acids) routinely performed in 274 nonsyndromic ASD children. RESULTS: The metabolic parameters were in the normal range for all but 2 patients: one with unspecific creatine urinary excretion and the other with persistent 3-methylglutaconic aciduria. CONCLUSIONS: These data provide the largest ever reported cohort of ASD patients for whom a systematic metabolic workup has been performed; they suggest that such a routine metabolic screening does not contribute to the causative diagnosis of nonsyndromic ASD. They also emphasize that the prevalence of screened IMD in nonsyndromic ASD is probably not higher than in the general population (<0.5%). A careful clinical evaluation is probably more reasonable and of better medical practice than a costly systematic workup.
