1. Fatemi SH, Folsom TD, Kneeland RE, Yousefi MK, Liesch SB, Thuras PD. {{Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex}}. {Mol Autism};2013 (Jun 26);4(1):21.
BACKGROUND: Candidate genes associated with idiopathic forms of autism overlap with other disorders including fragile X syndrome. Our laboratory has previously shown reduction in fragile X mental retardation protein (FMRP) and increase in metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and superior frontal cortex (BA9) of individuals with autism. METHODS: In the current study we have investigated expression of four targets of FMRP and mGluR5 signaling – homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP) – in the cerebellar vermis and superior frontal cortex (BA9) via SDS-PAGE and western blotting. Data were analyzed based on stratification with respect to age (children and adolescents vs. adults), anatomic region of the brain (BA9 vs. cerebellar vermis), and impact of medications (children and adolescents on medications (n = 4) vs. total children and adolescents (n = 12); adults on medications (n = 6) vs. total adults (n = 12)). RESULTS: There were significant increases in RAC1, APP 120 kDa and APP 80 kDa proteins in BA9 of children with autism vs. healthy controls. None of the same proteins were significantly affected in cerebellar vermis of children with autism. In BA9 of adults with autism there were significant increases in RAC1 and STEP 46 kDa and a significant decrease in homer 1 vs. controls. In the vermis of adult subjects with autism, RAC1 was significantly increased while APP 120, STEP 66 kDa, STEP 27 kDa, and homer 1 were significantly decreased when compared with healthy controls. No changes were observed in vermis of children with autism. There was a significant effect of anticonvulsant use on STEP 46 kDa/beta-actin and a potential effect on homer 1/NSE, in BA9 of adults with autism. However, no other significant confound effects were observed in this study. CONCLUSIONS: Our findings provide further evidence of abnormalities in FMRP and mGluR5 signaling partners in brains of individuals with autism and open the door to potential targeted treatments which could help ameliorate the symptoms of autism.
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2. Jascenoka J, Petermann U, Petermann F, Rissling JK, Springer S. {{[Short- and long-term effects of parent training programmes of children with developmental disabilities]}}. {Prax Kinderpsychol Kinderpsychiatr};2013;62(5):348-367.
Due to the higher care needs of their children, parents of children with developmental disabilities are often burdened. An increased degree of stress correlates with dysfunctional parenting behaviour and a low sense of competence. Parent involvement in treatment implementation is essential so that parents can support the development of their children long-ranging and positively. Parenting training programmes are an appropriate method to reduce child behaviou problems. The effectiveness of two parenting training programmes is presented: Intervention A involves weekly training courses containing information about a normative child development. Furthermore all parents are given the possibility to take part in therapy sessions. Intervention B is modular and high structured. Parents are taught in small groups and receive information about the different areas of development and how to increase their parentin behaviour. The outcomes of a randomized clinical trial of the two intervention concepts are presented. 34 parents with children (between 54 and 77 months) with developmental dis abilities participated per group. Particularly, intervention B was associated with a reduction of dysfunctional parenting behaviour and fewer child behaviour problems; a decreased parental stress level was observed for both interventions similarly.
3. M OH, Sweeney J, Doody O. {{Exploring fathers’ perceptions of parenting a child with Asperger syndrome}}. {J Intellect Disabil};2013 (Jun 26)
This study explores Irish fathers’ perceptions of parenting a child with Asperger syndrome (AS). Ethical approval was granted by the service provider, and Husserlian phenomenological approach facilitated the exploration. Data were collected through semi-structured interviews of nine fathers in the West region of Ireland. Data were transcribed and analysed using Colaizzi’s (1978) method. The study highlighted that parenting a child with AS is an arduous task, but while there are difficulties, many positive aspects to their parenting experience were reported. Overall, the study highlights the importance of listening to parents and their initial concerns regarding their child’s development.
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4. Miyake K, Yang C, Minakuchi Y, Ohori K, Soutome M, Hirasawa T, Kazuki Y, Adachi N, Suzuki S, Itoh M, Goto YI, Andoh T, Kurosawa H, Oshimura M, Sasaki M, Toyoda A, Kubota T. {{Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome}}. {PLoS One};2013;8(6):e66729.
Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.
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5. Uddin LQ, Supekar K, Lynch CJ, Khouzam A, Phillips J, Feinstein C, Ryali S, Menon V. {{Salience Network-Based Classification and Prediction of Symptom Severity in Children With Autism}}. {JAMA Psychiatry};2013 (Jun 26):1-11.
IMPORTANCE Autism spectrum disorder (ASD) affects 1 in 88 children and is characterized by a complex phenotype, including social, communicative, and sensorimotor deficits. Autism spectrum disorder has been linked with atypical connectivity across multiple brain systems, yet the nature of these differences in young children with the disorder is not well understood. OBJECTIVES To examine connectivity of large-scale brain networks and determine whether specific networks can distinguish children with ASD from typically developing (TD) children and predict symptom severity in children with ASD. DESIGN, SETTING, AND PARTICIPANTS Case-control study performed at Stanford University School of Medicine of 20 children 7 to 12 years old with ASD and 20 age-, sex-, and IQ-matched TD children. MAIN OUTCOMES AND MEASURES Between-group differences in intrinsic functional connectivity of large-scale brain networks, performance of a classifier built to discriminate children with ASD from TD children based on specific brain networks, and correlations between brain networks and core symptoms of ASD. RESULTS We observed stronger functional connectivity within several large-scale brain networks in children with ASD compared with TD children. This hyperconnectivity in ASD encompassed salience, default mode, frontotemporal, motor, and visual networks. This hyperconnectivity result was replicated in an independent cohort obtained from publicly available databases. Using maps of each individual’s salience network, children with ASD could be discriminated from TD children with a classification accuracy of 78%, with 75% sensitivity and 80% specificity. The salience network showed the highest classification accuracy among all networks examined, and the blood oxygen-level dependent signal in this network predicted restricted and repetitive behavior scores. The classifier discriminated ASD from TD in the independent sample with 83% accuracy, 67% sensitivity, and 100% specificity. CONCLUSIONS AND RELEVANCE Salience network hyperconnectivity may be a distinguishing feature in children with ASD. Quantification of brain network connectivity is a step toward developing biomarkers for objectively identifying children with ASD.
