1. Bashir S, Halepoto DM, Al-Ayadhi L. {{Serum Level of Desert Hedgehog Protein in Autism Spectrum Disorder: Preliminary Results}}. {Medical principles and practice : international journal of the Kuwait University, Health Science Centre}. 2013 Aug 31.
Objective: To investigate the role of desert hedgehog (Dhh) in a neurodevelopmental disorder known as autism. Subjects and Methods: This study was conducted at the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from October 2011 to May 2012. The serum levels of the Dhh protein in 57 patients recently diagnosed with autism and 37 age-matched healthy children were measured using ELISA. The Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. Results: The mean serum level of Dhh in patients with autism (1.38 +/- 0.50 ng/ml) was significantly lower (p = 0.0003) than that of normal controls (1.73 +/- 0.37 ng/ml). There was no significant relationship between the serum level of Dhh and the CARS score (p = 0.28), age (p = 0.51) or gender (p = 0.76). Conclusions: The Dhh serum level of patients with autism was lower than that of controls, probably indicating that the serum level of Dhh might be implicated in the physiology of autism. However, this finding should be treated with caution until further investigations are performed with larger populations. (c) 2013 S. Karger AG, Basel.
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2. Chamberlain PD, Rodgers J, Crowley MJ, White SE, Freeston MH, South M. {{A potentiated startle study of uncertainty and contextual anxiety in adolescents diagnosed with autism spectrum disorder}}. {Molecular autism}. 2013 Sep 4;4(1):31.
BACKGROUND: Beyond the core symptoms of autism spectrum disorder (ASD), associated symptoms of anxiety can cause substantial impairment for individuals affected by ASD and those who care for them. METHODS: We utilized a potentiated startle paradigm with a puff of air to the neck as the unconditioned stimulus in order to investigate differences between response to cued fear and contextual anxiety among cognitively able adolescents diagnosed with ASD and an age- and IQ-matched typically developing group. RESULTS: In a threat-modulated startle paradigm, response patterns to neutral, predictable, and unpredictable conditions were comparable across typically developing and ASD youth in terms of startle response magnitude and latency. However, the ASD group showed significantly greater absolute startle responsivity at baseline and throughout the experiment, suggesting possibly enhanced general sensitivity to threatening contexts. The ASD group, but not the control group, demonstrated moderate to strong negative correlations between psychophysiological response to unpredictable threats (uncertainty) and questionnaire measures of generalized anxiety, intolerance of uncertainty, and repetitive behavior. CONCLUSIONS: Our data suggest enhanced general reactivity among the ASD group, possibly reflecting greater sensitivity to the threatening context of the startle paradigm. Associations with the response to uncertainty may help explain shared neurobehavioral mechanisms in ASD and anxiety. This task can provide useful targets for future neuroimaging and genetics studies as well as specific avenues for intervention. We emphasize the importance of further basic and clinical research into links among these important constructs.
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3. Koegel RL, Bradshaw JL, Ashbaugh K, Koegel LK. {{Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment}}. {J Autism Dev Disord}. 2013 Sep 7.
Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social question-asking for three young children with autism was assessed. Results indicated that participants initiated a greater number of targeted questions following intervention. Additionally, all children exhibited increases in initiation of untargeted questions during social interaction in novel settings. Furthermore, post intervention data revealed collateral gains in communication and adaptive behavior. Theoretical implications of incorporating motivational strategies into intervention to improve social initiations in young children with ASD are discussed.
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4. Kratovac S, Corbin JG. {{Developmental changes in expression of inhibitory neuronal proteins in the Fragile X Syndrome mouse basolateral amygdala}}. {Brain research}. 2013 Sep 2.
In humans, Fragile X Syndrome (FXS) is characterized by enhanced fear, hyperactivity, social anxiety, and, in a subset of individuals, autism. Many of the emotional and social deficits point to defects in the amygdala. We have previously shown defects in inhibitory neuron drive onto excitatory projection neurons in the basolateral amygdala (BLA) of juvenile Fmr1-/y knockout (KO) mice. Using pharmacological approaches, we have also previously revealed dynamic functional deficits in alpha1, alpha2, and alpha3 subunit-containing GABAA receptors (GABAARs alpha1, alpha2, and alpha3) during early postnatal development. In this study, we sought to determine whether these defects in GABAAR function are accompanied by changes in protein expression of GABAARs alpha1, alpha2, and alpha3 and the post-synaptic GABAAR-clustering protein gephyrin. Interestingly, we found that while the expression of these proteins did not significantly differ between wildtype (WT) and KO mice at each time point, the timing of developmental expression of GABAAR alpha1, alpha2, and gephyrin was altered. Collectively, these data reveal novel defects in inhibitory synapse protein expression during critical periods of early postnatal development that could contribute to observed inhibitory neurotransmission deficits in the KO mouse BLA.
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5. Persicke A, Jackson M, Adams AN. {{Brief Report: An Evaluation of TAGteach Components to Decrease Toe-Walking in a 4-Year-Old Child with Autism}}. {J Autism Dev Disord}. 2013 Sep 6.
The current study evaluated the effectiveness of using a modified TAGteach procedure and correction to decrease toe-walking in a 4-year-old boy with autism. Two conditions were analyzed: correction alone and correction with an audible conditioned reinforcing stimulus. Correction alone produced minimal and inconsistent decreases in toe-walking but correction with an audible conditioned stimulus proved most effective in reducing this behavior. This has implications for decreasing toe-walking in other children with autism and may be easily used by teachers and parents.
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6. Stamova BS, Tian Y, Nordahl CW, Shen MD, Rogers S, Amaral DG, Sharp FR. {{Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders}}. {Molecular autism}. 2013 Sep 4;4(1):30.
BACKGROUND: Since RNA expression differences have been reported in autism spectrum disorder (ASD) for blood and brain, and differential alternative splicing (DAS) has been reported in ASD brains, we determined if there was DAS in blood mRNA of ASD subjects compared to typically developing (TD) controls, as well as in ASD subgroups related to cerebral volume. METHODS: RNA from blood was processed on whole genome exon arrays for 2-4–year-old ASD and TD boys. An ANCOVA with age and batch as covariates was used to predict DAS for ALL ASD (n=30), ASD with normal total cerebral volumes (NTCV), and ASD with large total cerebral volumes (LTCV) compared to TD controls (n=20). RESULTS: A total of 53 genes were predicted to have DAS for ALL ASD versus TD, 169 genes for ASD_NTCV versus TD, 1 gene for ASD_LTCV versus TD, and 27 genes for ASD_NTCV versus ASD_LTCV. These differences were significant at P <0.05 after false discovery rate corrections for multiple comparisons (FDR <5% false positives). A number of the genes predicted to have DAS in ASD are known to regulate DAS (SFPQ, SRPK1, SRSF11, SRSF2IP, FUS, LSM14A). In addition, a number of genes with predicted DAS are involved in pathways implicated in previous ASD studies, such as ROS monocyte/macrophage, Natural Killer Cell, mTOR, and NGF signaling. The only pathways significant after multiple comparison corrections (FDR <0.05) were the Nrf2-mediated reactive oxygen species (ROS) oxidative response (superoxide dismutase 2, catalase, peroxiredoxin 1, PIK3C3, DNAJC17, microsomal glutathione S-transferase 3) and superoxide radical degradation (SOD2, CAT). CONCLUSIONS: These data support differences in alternative splicing of mRNA in blood of ASD subjects compared to TD controls that differ related to head size. The findings are preliminary, need to be replicated in independent cohorts, and predicted alternative splicing differences need to be confirmed using direct analytical methods.
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7. Velmeshev D, Magistri M, Faghihi MA. {{Expression of non-protein-coding antisense RNAs in genomic regions related to autism spectrum disorders}}. {Molecular autism}. 2013 Sep 4;4(1):32.
BACKGROUND: Autism spectrum disorders (ASD) manifest with neurodevelopmental phenotypes including communicative, social and behavioral impairments that affect as many as 1 in 88 children. The majority of autism cases have no known genetic cause, suggesting complex genetics of the disorder, but a few genes of large effect have been identified. METHODS: In order to identify novel ASD genetic correlates, we investigated non-protein coding RNAs (ncRNAs) which are abundantly transcribed from the human genome, enriched in the brain, and have been implicated in neurodevelopmental disorders. Using an algorithm that we developed, we examined a publicly available transcriptomics database, AceView, to identify the ncRNA natural antisense transcripts (NATs) that overlap with known autism-related genes. We validated the presence and differential expression of NATs in different brain regions of ASD and control brains using qRT-PCR. Additionally, we investigated the subcellular localization of these transcripts in a neuronal cell line using RNA-sequencing (RNA-seq). RESULTS: We found noncoding antisense RNA transcripts at approximately 40% of loci previously implicated in ASD. We confirmed the expression of 10 antisense RNAs in different postmortem human brain tissues. The expression of five antisense transcripts was found to be region-specific, suggesting a role for these ncRNAs in the development and function of specific brain regions. Some antisense RNAs overlapping suspected ASD genes exhibited concordant expression relative to their sense protein-coding genes, while other sense-antisense pairs demonstrate a discordant relationship. Interestingly, the antisense RNA corresponding to the SYNGAP1 locus (SYNGAP1-AS) was found to be differentially expressed in brain regions of patients with ASD compared to control individuals. RNA-seq analysis of subcellular compartments from SH-SY5Y human neuroblastoma cells demonstrated that antisense RNAs to ASD candidate genes are predominantly expressed in the nucleoplasmic or chromatin compartments, implying their involvement in nuclear-associated processes. CONCLUSIONS: Our data suggests that NATs are abundantly expressed from ASD-related loci and provide evidence for their roles in target gene regulation, neurodevelopment and autism pathogenesis. This class of RNA should therefore be considered in functional studies aimed at understanding genetic risk factors for ASD.
