1. Gaetz W, Bloy L, Wang DJ, Port RG, Blaskey L, Levy SE, Roberts TP. {{GABA estimation in the Brains of Children on the Autism Spectrum: Measurement precision and regional cortical variation}}. {NeuroImage}. 2013 May 23.
1H-magnetic resonance spectroscopy (1H-MRS) and spectral editing methods, such as MEGA-PRESS, allow researchers to investigate metabolite and neurotransmitter concentrations in-vivo. Here we address the utilization of 1H-MRS for the investigation of GABA concentrations in the ASD brain, in three locations; motor, visual and auditory areas. An initial repeatability study (5 subjects, 5 repeated measures separated by~5days on average) indicated no significant effect of reference metabolite choice on GABA quantitation (p>0.6). Coefficients of variation for GABA+/NAA, GABA+/Cr and GABA+/Glx were all of the order of 9-11%. Based on these findings, we investigated creatine-normalized GABA+ratios (GABA+/Cr) in a group of (n=17) children with autism spectrum disorder (ASD) and (n=17) typically developing children (TD) for Motor, Auditory and Visual regions of interest (ROIs). Linear regression analysis of grey matter (GM) volume changes (known to occur with development) revealed a significant decrease of GM volume with Age for Motor (F(1,30)=17.92; p<0.001) and Visual F(1,16)=14.41; p<0.005 but not the Auditory ROI(p=0.55). Inspection of GABA+/Cr changes with Age revealed a marginally significant change for the Motor ROI only (F(1,30)=4.11; p=0.054). Subsequent analyses was thus conducted for each ROI separately using Age and GM volume as covariates. No group differences in GABA+/Cr were observed for the Visual ROI between TD vs. ASD children. However, the Motor and Auditory ROI showed significantly reduced GABA+/Cr in ASD (Motor p<0.05; Auditory p<0.01). The mean deficiency in GABA+/Cr from the Motor ROI was approximately 11% and Auditory ROI was approximately 22%. Our novel findings support the model of regional differences in GABA+/Cr in the ASD brain, primarily in Auditory and to a lesser extent Motor but not Visual areas.
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2. Hahr JY. {{Iatrogenic autism}}. {Medical hypotheses}. 2013 May 21.
Autism as we know it, is caused iatrogenically and occurs reportedly one in 88 live birth [3]. Now national survey pegs autism prevalence one in 50 school-age children and the incidence is rising much fast in recent years. The author is hypothesizing idiopathic autism is caused by feeding of infant formula. Majorities of formula in the world are milk based and the molecular weight of the cow’s milk is much higher than that of human breast milk. These increased solutes contributes to increased osmolality of the environment of the newborn infant, is directly affecting hemodynamics of normal homeostasis of the developing human brain cells. Formula makers fortified new substances in the process of formula making whenever they found previous unknown substances in the breast milk, for past several decades. When those solid substances were added in the process of formula making to make 20cal/oz of infant formula, this resulted displacing free water in the formula. When new substances were added, same amount of free water has to be displaced from the formula. That is why we are seeing more autism in recent years, compared to previous several decades.
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3. Konerding U. {{What does Cronbach’s alpha tell us about the EQ-5D? A methodological commentary to « Psychometric properties of the EuroQol Five-Dimensional Questionnaire (EQ-5D-3L) in caregivers of autistic children »}}. {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}. 2013 May 25.
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4. Lohith TG, Osterweil EK, Fujita M, Jenko KJ, Bear MF, Innis RB. {{Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome?}}. {Molecular autism}. 2013 May 24;4(1):15.
BACKGROUND: Fragile X syndrome (FXS) is a common inherited form of intellectual disability caused by loss of function of the fragile X mental retardation protein. Recent animal studies suggest that upregulated downstream signaling by metabotropic glutamate receptor 5 (mGluR5) might be an important mechanism for cognitive and behavioral abnormalities associated with FXS. However, mGluR5 density in human FXS remains unknown. METHODS: Receptor binding and protein expression were measured in the postmortem prefrontal cortex of 14 FXS patients or carriers and 17 age- and sex-matched control subjects without neurological disorders. In-vitro binding assays were performed using [3H]-labeled 3-methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity negative allosteric modulator of mGluR5, to measure receptor density and the radioligand’s dissociation constant, which is inversely proportional to affinity. Immunoblotting was also performed, to measure mGluR5 protein expression. RESULTS: The mGluR5 density increased with marginal significance (+16%; P = 0.058) in the prefrontal cortex of FXS patients or carriers compared with matched healthy controls. No significant change in dissociation constant (-4%; P = 0.293) was observed. Immunoblotting found a significant elevation (+32%; P = 0.048) in mGluR5 protein expression. CONCLUSIONS: Both mGluR5 binding density and protein expression were increased in the brains of FXS patients or carriers, but only expression was significantly different, which could be because of the small sample size and moderate variability. Another important caveat is that the effects of psychotropic medications on mGluR5 expression are largely unknown. Future in-vivo measurement of mGluR5 with positron emission tomography might characterize the role of this receptor in the pathophysiology of FXS and facilitate trials of mGluR5-oriented treatments for this disorder.
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5. Raznahan A, Wallace GL, Antezana L, Greenstein D, Lenroot R, Thurm A, Gozzi M, Spence S, Martin A, Swedo SE, Giedd JN. {{Compared to What? Early Brain Overgrowth in Autism and the Perils of Population Norms}}. {Biol Psychiatry}. 2013 May 23.
BACKGROUND: Early brain overgrowth (EBO) in autism spectrum disorder (ASD) is among the best replicated biological associations in psychiatry. Most positive reports have compared head circumference (HC) in ASD (an excellent proxy for early brain size) with well-known reference norms. We sought to reappraise evidence for the EBO hypothesis given 1) the recent proliferation of longitudinal HC studies in ASD, and 2) emerging reports that several of the reference norms used to define EBO in ASD may be biased toward detecting HC overgrowth in contemporary samples of healthy children. METHODS: Systematic review of all published HC studies in children with ASD. Comparison of 330 longitudinally gathered HC measures between birth and 18 months from male children with autism (n = 35) and typically developing control subjects (n = 22). RESULTS: In systematic review, comparisons with locally recruited control subjects were significantly less likely to identify EBO in ASD than norm-based studies (p < .001). Through systematic review and analysis of new data, we replicate seminal reports of EBO in ASD relative to classical HC norms but show that this overgrowth relative to norms is mimicked by patterns of HC growth age in a large contemporary community-based sample of US children (n ~ 75,000). Controlling for known HC norm biases leaves inconsistent support for a subtle, later emerging and subgroup specific pattern of EBO in clinically ascertained ASD versus community control subjects. CONCLUSIONS: The best-replicated aspects of EBO reflect generalizable HC norm biases rather than disease-specific biomarkers. The potential HC norm biases we detail are not specific to ASD research but apply throughout clinical and academic medicine.
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6. Schlosser RW, Laubscher E, Sorce J, Koul R, Flynn S, Hotz L, Abramson J, Fadie H, Shane H. {{Implementing Directives that Involve Prepositions with Children with Autism: A Comparison of Spoken Cues with Two Types of Augmented Input}}. {Augmentative and alternative communication (Baltimore, Md : 1985)}. 2013 Jun;29(2):132-45.
Abstract Some children with autism face considerable challenges with comprehension, including difficulties following spoken directives involving prepositional relations. The use of augmented input through visual modalities might be an effective means for supplementing spoken language. The purpose of this preliminary study was to compare spoken input with two augmented input modalities (i.e., speech + visual cues) in terms of children’s ability to follow directives involving prepositions. The augmented input modalities consisted of static scene cues (i.e., photographic or pictorial visual scenes that portray relevant concepts and their relationships) and dynamic scene cues (i.e., full-motion video clips that depict the actions underlying relevant concepts and their relationships). A within-subjects design involving nine children with autism or pervasive developmental disorders-not otherwise specified was used to examine the effectiveness of the three input conditions. Results indicated that both static scene cues and dynamic scene cues were more effective than spoken cues, but there were no differences between static scene cues and dynamic scene cues. Results are discussed in terms of appropriate instructional inputs for children with autism. Limitations are noted and directions for future research are posited.
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7. Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Yong Ma S, Azmitia EC, Banerjee P, Flory M, Cohen IL, London E, Ted Brown W, Komich Hare C, Wisniewski T. {{Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism}}. {Brain research}. 2013 May 28;1512:106-22.
Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects of the oculomotor system, including avoidance of eye contact and poor or no eye contact, were reported in 88% of autistic subjects with postmortem-detected floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs); deficit and abnormalities of granule, basket, stellate and unipolar brush cells; and structural defects and abnormal orientation of Bergmann glia are indicators of profound disruption of flocculus circuitry in a dysplastic area. The average volume of PCs was 26% less in the dysplastic region than in the unaffected region of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of PCs in the entire cerebellum was 25% less in the autistic subjects than in the control subjects (p<0.001). Findings from this study and a parallel study of the inferior olive (IO) suggest that focal floccular dysplasia combined with IO neurons and PC developmental defects may contribute to oculomotor system dysfunction and atypical gaze in autistic subjects.
