1. Bello O, Blair K, Chapleau C, Larimore JL. {{Is memantine a potential therapeutic for Rett syndrome?}}. {Front Neurosci}. 2013; 7: 245.
Memantine is a low-affinity, voltage-dependent, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is classified as a neuroprotective aminoadamantane. It does not cure or reverse Alzheimer’s but it does effectively treat symptoms, slows the progression of the disease and allows many patients to perform daily cognitive activities with clear thoughts. Based on it’s success in patients with Alzheimer’s, memantine has been tested in other neurological disorders with impaired learning and memory. In this review, we will discuss the success and failures of memantine in Downs Syndrome and Fragile X research and from those results, assess the potential benefit of memantine in Rett Syndrome (RTT).
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2. Chomiak T, Turner N, Hu B. {{What We Have Learned about Autism Spectrum Disorder from Valproic Acid}}. {Patholog Res Int}. 2013; 2013: 712758.
Two recent epidemiological investigations in children exposed to valproic acid (VPA) treatment in utero have reported a significant risk associated with neurodevelopmental disorders and autism spectrum disorder (ASD) in particular. Parallel to this work, there is a growing body of animal research literature using VPA as an animal model of ASD. In this focused review we first summarize the epidemiological evidence linking VPA to ASD and then comment on two important neurobiological findings linking VPA to ASD clinicopathology, namely, accelerated or early brain overgrowth and hyperexcitable networks. Improving our understanding of how the drug VPA can alter early development of neurological systems will ultimately improve our understanding of ASD.
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3. Ghaziuddin M, Welch K. {{The michigan autism spectrum questionnaire: a rating scale for high-functioning autism spectrum disorders}}. {Autism Res Treat}. 2013; 2013: 708273.
Although the DSM-5 has recently created a single category of autism spectrum disorder (ASD), delineation of its putative subtypes remains clinically useful. For this process, screening instruments should ideally be brief, simple, and easily available. The aim of this study is to describe the validity of one such instrument. We administered the Michigan Autism Spectrum Questionnaire (MASQ), a 10-item questionnaire, to 42 patients with ASD (age range 6-13 years, mean 9.7 years, SD 2.5, one female) and 18 patients with other psychiatric disorders (age range 6-17 years, mean 11.7 years, SD 3.8, 6 females). Responses to each item were scored from 0 to 4 yielding a total score of 30. Patients with intellectual disability were excluded. As a group, patients with ASD scored higher than those with other psychiatric disorders (Chi-square test with 1 df = 16.019, P < 0.0001). Within the ASD group, a linear discriminant analysis found that the best cut-off points were 22 or above for Asperger syndrome, 14 to 21 for autism/PDDNOS, and less than 14 for those with other psychiatric disorders. We propose that the MASQ can be used as a brief measure to screen high-functioning ASD from other psychiatric disorders and to identify its possible subtypes.
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4. Kumar S, Karmakar P, Mohanan A. {{Language regression in children with Autism Spectrum Disorders}}. {Int J Pediatr Otorhinolaryngol}. 2013.
OBJECTIVES: Regression in autism applies to the phenomenon of apparently normal early development followed by the loss of previously acquired skills and manifestation of symptoms of autism. Estimates of the frequency of regression in autism range from 10% to 50%. Although there are tools available to evaluate and diagnose Autism Spectrum Disorders, however, there is no published tool available in Indian context to identify the children with ASD at an early age. The study was aimed to describe the differences in language regression between children with ASD and typically developing children and also to determine the age of regression. METHODS: Regression screening tool, a questionnaire was developed based on Regression Supplement Form (Goldberg et al., 2003). The skills were validated by five Clinical Psychologists. It comprised of 16 skills which included domains like, ‘spoken language and non verbal communication’, ‘social interest and responsiveness’ and ‘play and imagination’. This retrospective study was conducted on a single group. The participants consisted of parents of 30 children with ASD (22 males and 8 females). RESULTS: The findings revealed a significant regression in children with ASD. The mean regression age is 20.19 months (SD-5.2). The regression profile of the children with ASD revealed regression of language skills occurred at 19.16 months followed by non language skills at 20.5 months. CONCLUSIONS: Based on the findings it can be stated that inclusion of regression screening tool will offer clinicians a convenient tool to examine the phenomena of regression in children with ASD and identify them as early as 21 months of age for early intervention.
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5. Lionel AC, Tammimies K, Vaags AK, Rosenfeld JA, Ahn JW, Merico D, Noor A, Runke CK, Pillalamarri VK, Carter MT, Gazzellone MJ, Thiruvahindrapuram B, Fagerberg C, Laulund LW, Pellecchia G, Lamoureux S, Deshpande C, Clayton-Smith J, White AC, Leather S, Trounce J, Bedford HM, Hatchwell E, Eis PS, Yuen RK, Walker S, Uddin M, Geraghty MT, Nikkel SM, Tomiak EM, Fernandez BA, Soreni N, Crosbie J, Arnold PD, Schachar RJ, Roberts W, Paterson AD, So J, Szatmari P, Chrysler C, Woodbury-Smith M, Lowry RB, Zwaigenbaum L, Mandyam D, Wei J, Macdonald JR, Howe JL, Nalpathamkalam T, Wang Z, Tolson D, Cobb DS, Wilks TM, Sorensen MJ, Bader PI, An Y, Wu BL, Musumeci SA, Romano C, Postorivo D, Nardone AM, Della Monica M, Scarano G, Zoccante L, Novara F, Zuffardi O, Ciccone R, Antona V, Carella M, Zelante L, Cavalli P, Poggiani C, Cavallari U, Argiropoulos B, Chernos J, Brasch-Andersen C, Speevak M, Fichera M, Ogilvie CM, Shen Y, Hodge JC, Talkowski ME, Stavropoulos DJ, Marshall CR, Scherer SW. {{Disruption of the ASTN2 / TRIM32 locus at 9q33.1 is a risk factor in males for Autism Spectrum Disorders, ADHD and other neurodevelopmental phenotypes}}. {Hum Mol Genet}. 2013.
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders. The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89,985 individuals across 10 sites, including 64,114 neurodevelopmental disorder subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the neurodevelopmental disorder subjects (p=0.002) compared with 44,085 population-based controls. Frequent phenotypes observed in individuals with such deletions included Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorder (ADHD), speech delay, anxiety and Obsessive Compulsive Disorder (OCD). The 3′-terminal ASTN2 deletions were significantly enriched compared with controls in males with neurodevelopmental disorders, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.
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6. Miranda ML, Anthopolos R, Gregory SG. {{Association of autism with induced or augmented childbirth – Authors’ Response}}. {Am J Obstet Gynecol}. 2013.
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7. Park S, Park JE, Cho SC, Kim BN, Shin MS, Kim JW, Cho IH, Kim SA, Park M, Park TW, Son JW, Chung US, Yoo HJ. {{No association of the norepinephrine transporter gene (SLC6A2) and cognitive and behavioural phenotypes of patients with autism spectrum disorder}}. {Eur Arch Psychiatry Clin Neurosci}. 2014.
We examined the association between the norepinephrine transporter (SLC6A2) gene and autism spectrum disorder (ASD) in a Korean population. In addition, we investigated which phenotypes of ASD are best attributed to the genotype of SLC6A2. A total of 184 subjects with ASD, their 156 unaffected siblings and both biological parents were recruited through university hospitals. We used the Autism Diagnostic Interview-Revised, the Aberrant Behaviour Checklist (ABC), the Child Behaviour Checklist (CBCL), the Stroop Colour-Word Interference Test and the Wisconsin Card Sorting Test (WCST) as quantitative measures of the ASD phenotypes. The associations between the quantitative measures and specific single-nucleotide polymorphisms (SNPs) were tested with linear regression analyses. We did not find any evidence of the over-transmission of either allele of the 10SLC6A2 SNPs in the DFAM test. At an empirical p value <0.05, findings that were consistent between the linear regression analyses and the QFAM tests were the positive associations between the A allele of rs36020 and attention problems on the CBCL and stereotypical behaviours on the ABC and between the C allele of rs1814270 and the number of trials required to complete the first WCST category. However, these associations did not remain after correction for multiple testing. The study results of this study do not support the association between the SLC6A2 and the diagnosis or phenotype of ASD. However, the study must be replicated in larger populations and with using more genetic markers.
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8. Roberts JE, Tonnsen BL, Robinson M, McQuillin SD, Hatton DD. {{Temperament factor structure in fragile X syndrome: The Children’s Behavior Questionnaire}}. {Res Dev Disabil}. 2013; 35(2): 563-71.
Early patterns of temperament lay the foundation for a variety of developmental constructs such as self-regulation, psychopathology, and resilience. Children with fragile X syndrome (FXS) display unique patterns of temperament compared to age-matched clinical and non-clinical samples, and early patterns of temperament have been associated with later anxiety in this population. Despite these unique patterns in FXS and recent reports of atypical factor structure of temperament questionnaires in Williams Syndrome (Leyfer, John, Woodruff-Borden, & Mervis, 2012), no studies have examined the latent factor structure of temperament scales in FXS to ensure measurement validity in this sample. The present study used confirmatory factor analysis to examine the factor structure of a well-validated parent-reported temperament questionnaire, the Children’s Behavior Questionnaire (Rothbart, Ahadi, Hershey, & Fisher, 2001), in a sample of 90 males with FXS ages 3-9 years. Our data produced a similar, but not identical, three-factor model that retained the original CBQ factors of negative affectivity, effortful control, and extraversion/surgency. In particular, our FXS sample demonstrated stronger factor loadings for fear and shyness than previously reported loadings in non-clinical samples, consistent with reports of poor social approach and elevated anxiety in this population. Although the original factor structure of the Children’s Behavior Questionnaire is largely retained in children with FXS, differences in factor loading magnitudes may reflect phenotypic characteristics of the syndrome. These findings may inform future developmental and translational research efforts.
