1. Brady NC, Anderson CJ, Hahn LJ, Obermeier SM, Kapa LL. {{Eye Tracking as a Measure of Receptive Vocabulary in Children with Autism Spectrum Disorders}}. {Augment Altern Commun}. 2014.
This study examined the utility of eye tracking research technology to measure speech comprehension in 14 young boys with autism spectrum disorders (ASD) and 15 developmentally matched boys with typical development. Using eye tracking research technology, children were tested on individualized sets of known and unknown words, identified based on their performance on the Peabody Picture Vocabulary Test. Children in both groups spent a significantly longer amount of time looking at the target picture when previous testing indicated the word was known (known condition). Children with ASD spent similar amounts of time looking at the target and non-target pictures when previous testing indicated the word was unknown (unknown condition). However, children with typical development looked longer at the target pictures in the unknown condition as well, potentially suggesting emergent vocabulary knowledge.
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2. Gillespie-Smith K, Fletcher-Watson S. {{Designing AAC Systems for Children with Autism: Evidence from Eye Tracking Research}}. {Augment Altern Commun}. 2014.
Autism is associated with a range of language difficulties that impact communication, behaviour management, and education. Consequently, a variety of augmentative and alternative communication (AAC) strategies may be employed to support people with autism to communicate. There is a growing body of evidence concerning the visual attention of individuals with autism, which may be relevant to AAC interventions. This review draws on evidence from eye tracking research specifically to inform the design of AAC systems for people with autism. In addition, we discuss the future of AAC for individuals with autism in light of relevant technological developments, and raise questions for future research.
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3. Wilkinson KM, Light J. {{Preliminary Study of Gaze Toward Humans in Photographs by Individuals with Autism, Down Syndrome, or Other Intellectual Disabilities: Implications for Design of Visual Scene Displays}}. {Augment Altern Commun}. 2014.
Visual scene displays (VSDs) are a form of augmentative and alternative communication display in which language concepts are embedded into an image of a naturalistic event. VSDs are based on the theory that language learning occurs through interactions with other people, and recommendations for VSD design have emphasized using images of these events that include humans. However, many VSDs also include other items that could potentially be distracting. We examined gaze fixation in 18 school-aged participants with and without severe intellectual/developmental disabilities (i.e., individuals with typical development, autism, Down syndrome and other intellectual disabilities) while they viewed photographs with human figures of various sizes and locations in the image, appearing alongside other interesting, and potentially distracting items. In all groups, the human figures attracted attention rapidly (within 1.5 seconds). The proportions of each participant’s own fixation time spent on the human figures were similar across all groups, as were the proportions of total fixations made to the human figures. Although the findings are preliminary, this initial evidence supports the inclusion of humans in VSD images.
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4. Johnson RA, Danis M, Hafner-Eaton C. {{US state variation in autism insurance mandates: Balancing access and fairness}}. {Autism}. 2014.
This article examines how nations split decision-making about health services between federal and sub-federal levels, creating variation between states or provinces. When is this variation ethically acceptable? We identify three sources of ethical acceptability-procedural fairness, value pluralism, and substantive fairness-and examine these sources with respect to a case study: the fact that only 30 out of 51 US states or territories passed mandates requiring private insurers to offer extensive coverage of autism behavioral therapies, creating variation for privately insured children living in different US states. Is this variation ethically acceptable? To address this question, we need to analyze whether mandates go to more or less needy states and whether the mandates reflect value pluralism between states regarding government’s role in health care. Using time-series logistic regressions and data from National Survey of Children with Special Health Care Needs, Individual with Disabilities Education Act, legislature political composition, and American Board of Pediatrics workforce data, we find that the states in which mandates are passed are less needy than states in which mandates have not been passed, what we call a cumulative advantage outcome that increases between-state disparities rather than a compensatory outcome that decreases between-state disparities. Concluding, we discuss the implications of our analysis for broader discussions of variation in health services provision.
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5. Pellicano E, Dinsmore A, Charman T. {{What should autism research focus upon? Community views and priorities from the United Kingdom}}. {Autism}. 2014.
The rise in the measured prevalence of autism has been accompanied by much new research and research investment internationally. This study sought to establish whether the pattern of current UK autism research funding maps on to the concerns of the autism community. Interviews and focus groups were conducted with autistic adults, family members, practitioners and researchers to identify their priorities for research. We also captured the views of a large number of stakeholders via an online survey. There was a clear disparity between the United Kingdom’s pattern of funding for autism research and the priorities articulated by the majority of participants. There was general consensus that future priorities for autism research should lie in those areas that make a difference to people’s day-to-day lives. There needs to be greater involvement of the autism community both in priority setting and in research more broadly to ensure that resources reach where they are most needed and can make the most impact.
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6. Hauth I, de Bruijn YG, Staal W, Buitelaar JK, Rommelse NN. {{Testing the Extreme Male Brain Theory of Autism Spectrum Disorder in a Familial Design}}. {Autism Res}. 2014.
Autism Spectrum Disorder (ASD) may be an extreme manifestation of some male-typical traits in both neuroanatomy and cognition. Using the ratio of the second to fourth digit (2D:4D) and digit length as biomarkers of (pre- and postnatal) testosterone levels, examined was whether hypermasculinized digit ratios and/or lengths were familial traits in ASD and investigated their relation to sexually dimorphic cognitive abilities. 2D:4D ratios and digit lengths of 216 children with ASD, 202 unaffected siblings, and 360 parents were compared with those of 174 control children and their 146 parents. Generalized Estimation Equations, Generalized Linear Models, and Linear Mixed Models were used to investigate parent-offspring relationships and group differences. In ASD probands and their relatives alike, digit length relative to overall height was significantly increased in comparison to controls. No significant group differences were found between affected and unaffected subjects, or between males and females. Additionally, 2D:4D ratios increased with age. No (consistent) associations were found between 2D:4D ratio or digit lengths and systemizing and empathizing skills. The findings emphasize the role of familially based elevated pre- and postnatal testosterone levels in the liability for ASD, but challenge the use of 2D:4D ratio as a proxy of prenatal testosterone exposure solely. Given that many genes influence digit length, the exact mechanisms underlying a familial predisposition toward increased digit length in ASD are as yet unknown and needs to be explored in future studies. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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7. McCormick C, Hessl D, Macari SL, Ozonoff S, Green C, Rogers SJ. {{Electrodermal and Behavioral Responses of Children With Autism Spectrum Disorders to Sensory and Repetitive Stimuli}}. {Autism Res}. 2014.
Parents frequently report that their children with autism spectrum disorders (ASD) respond atypically to sensory stimuli. Repetitive behaviors are also part of the ASD behavioral profile. Abnormal physiological arousal may underlie both of these symptoms. Electrodermal activity (EDA) is an index of sympathetic nervous system arousal. The goals of this study were twofold: (1) to pilot methods for collecting EDA data in young children and (2) to examine hypothesized relationships among EDA, and sensory symptoms and repetitive behaviors in children with ASD as compared with children with typical development. EDA was recorded on 54 young children with ASD and on 33 children with typical development (TD) during a protocol that included baseline, exposure to sensory and repetitive stimuli, and play. Parents completed standardized questionnaires regarding their child’s sensory symptoms and repetitive behaviors. Frequency and type of repetitive behavior during play was coded offline. Comparisons between EDA data for ASD and TD groups indicated no significant between-group differences in any measures. Parents of children with ASD reported more abnormal responses to sensory stimuli and more repetitive behaviors, but scores on these measures were not significantly correlated with EDA or with frequency of observed repetitive behaviors. Parent report of frequency and severity of sensory symptoms was significantly correlated with reports of repetitive behaviors in both groups. Although parents of children with ASD report high levels of sensory symptoms and repetitive behaviors, these differences are not related to measured EDA arousal or reactivity. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Eapen V, Crncec R, Walter A, Tay KP. {{Conceptualisation and development of a quality of life measure for parents of children with autism spectrum disorder}}. {Autism Res Treat}. 2014; 2014: 160783.
Parents of children with autism spectrum disorder (ASD) tend to experience greater psychological distress than parents of typically developing children or children with other disabilities. Quality of Life (QoL) is increasingly recognised as a critical outcome measure for planning and treatment purposes in ASD. There is a need for ASD-specific QoL measures as generic measures may not capture all relevant aspects of living with ASD. This paper describes the conceptualisation and development of an autism-specific measure of QoL, the Quality of Life in Autism Questionnaire (QoLA) for parents and caregivers of children with ASD, that is suitable to clinical and research settings. Preliminary psychometric properties (reliability and validity) of the measure are also presented. The QoLA has 48 items in two subscales: one comprising QoL items and the second a parent report of how problematic their child’s ASD symptoms are. A study involving 39 families suggested the QoLA has excellent internal consistency as well as good known-groups validity between parents of children with ASD and those who were typically developing. The QoLA also showed good convergent validity with other measures of QoL and ASD symptom severity, respectively. The QoLA may be a valuable assessment tool and merits further psychometric evaluation.
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9. Alabdali A, Al-Ayadhi L, El-Ansary A. {{A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders}}. {Behav Brain Funct}. 2014; 10(1): 14.
BACKGROUND: Autism Spectrum Disorders (ASD) is a syndrome with a number of etiologies and different mechanisms that lead to abnormal development. The identification of autism biomarkers in patients with different degrees of clinical presentation (i.e., mild, moderate and severe) will give greater insight into the pathogenesis of this disease and will enable effective early diagnostic strategies and treatments for this disorder. METHODS: In this study, the concentration of two toxic heavy metals, lead (Pb) and mercury (Hg), were measured in red blood cells, while glutathione-s-transferase (GST) and vitamin E, as enzymatic and non-enzymatic antioxidants, respectively, were measured in the plasma of subgroups of autistic patients with different Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS) scores. The results were compared to age- and gender-matched healthy controls. RESULTS: The obtained data showed that the patients with autism spectrum disorder had significantly higher Pb and Hg levels and lower GST activity and vitamin E concentrations compared with the controls. The levels of heavy metals (Hg and Pb), GST and vitamin E were correlated with the severity of the social and cognitive impairment measures (SRS and CARS). Receiver Operating Characteristics (ROC) analysis and predictiveness curves indicated that the four parameters show satisfactory sensitivity, very high specificity and excellent predictiveness. Multiple regression analyses confirmed that higher levels of Hg and Pb, together with lower levels of GST and vitamin E, can be used to predict social and cognitive impairment in patients with autism spectrum disorders. CONCLUSION: This study confirms earlier studies that implicate toxic metal accumulation as a consequence of impaired detoxification in autism and provides insight into the etiological mechanism of autism.
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10. Watkins N, Sparling E. {{The Effectiveness of the Snug Vest on Stereotypic Behaviors in Children Diagnosed With an Autism Spectrum Disorder}}. {Behav Modif}. 2014.
Various reviews of the effects of sensory integration therapy (SIT) have concluded that such interventions fail to reduce stereotypy. However, a new, and as yet untested, SIT iteration, an inflatable wearable vest known as the Snug Vest purports to decrease such repetitive behavior. In the current study, three children who emitted different forms of stereotypy participated in an alternating treatments design in which each participant wore a fully inflated vest and either a fully deflated vest or no vest. The results of the study show that the Snug Vest failed to reduce any participants’ stereotypy. We highlight our findings in the context of professional practice and discuss several potential limitations.
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11. Hamilton SM, Green JR, Veeraragavan S, Yuva L, McCoy A, Wu Y, Warren J, Little L, Ji D, Cui X, Weinstein E, Paylor R. {{Fmr1 and Nlgn3 knockout rats: Novel tools for investigating autism spectrum disorders}}. {Behav Neurosci}. 2014; 128(2): 103-9.
Animal models are critical for gaining insights into autism spectrum disorder (ASD). Despite their apparent advantages to mice for neural studies, rats have not been widely used for disorders of the human CNS, such as ASD, for the lack of convenient genome manipulation tools. Here we describe two of the first transgenic rat models for ASD, developed using zinc-finger nuclease (ZFN) methodologies, and their initial behavioral assessment using a rapid juvenile test battery. A syndromic and nonsyndromic rat model for ASD were created as two separate knockout rat lines with heritable disruptions in the genes encoding Fragile X mental retardation protein (FMRP) and Neuroligin3 (NLGN3). FMRP, a protein with numerous proposed functions including regulation of mRNA and synaptic protein synthesis, and NLGN3, a member of the neuroligin synaptic cell-adhesion protein family, have been implicated in human ASD. Juvenile subjects from both knockout rat lines exhibited abnormalities in ASD-relevant phenotypes including juvenile play, perseverative behaviors, and sensorimotor gating. These data provide important first evidence regarding the utility of rats as genetic models for investigating ASD-relevant genes. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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12. Inaba Y, Schwartz CE, Bui QM, Li X, Skinner C, Field M, Wotton T, Hagerman RJ, Francis D, Amor DJ, Hopper JL, Loesch DZ, Bretherton L, Slater HR, Godler DE. {{Early Detection of Fragile X Syndrome: Applications of a Novel Approach for Improved Quantitative Methylation Analysis in Venous Blood and Newborn Blood Spots}}. {Clin Chem}. 2014.
BACKGROUND: Standard fragile X syndrome (FXS) diagnostic tests that target methylation of the fragile X mental retardation 1 (FMR1) CpG island 5` of the CGG expansion can be used to predict severity of the disease in males from birth, but not in females.METHODS: We describe methylation specific-quantitative melt analysis (MS-QMA) that targets 10 CpG sites, with 9 within FMR1 intron 1, to screen for FXS from birth in both sexes. The novel method combines the qualitative strengths of high-resolution melt and the high-throughput, quantitative real-time PCR standard curve to provide accurate quantification of DNA methylation in a single assay. Its performance was assessed in 312 control (CGG <40), 143 premutation (PM) (CGG 56-170), 197 full mutation (FM) (CGG 200-2000), and 33 CGG size and methylation mosaic samples.RESULTS: In male and female newborn blood spots, MS-QMA differentiated FM from control alleles, with sensitivity, specificity, and positive and negative predictive values between 92% and 100%. In venous blood of FM females between 6 and 35 years of age, MS-QMA correlated most strongly with verbal IQ impairment (P = 0.002). In the larger cohort of males and females, MS-QMA correlated with reference methods Southern blot and MALDI-TOF mass spectrometry (P < 0.05), but was not significantly correlated with age. Unmethylated alleles in high-functioning FM and PM males determined by both reference methods were also unmethylated by MS-QMA.CONCLUSIONS: MS-QMA has an immediate application in FXS diagnostics, with a potential use of its quantitative methylation output for prognosis in both sexes.
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13. McLay L, Church J, Sutherland D. {{Variables affecting the emergence of untaught equivalence relations in children with and without autism}}. {Dev Neurorehabil}. 2014.
Abstract Objective: This study examined the formation of equivalence classes among children with ASD and typically developing children. Design: A single-subject AB and BA design was used. Methods: Two of the six equivalence relations were taught. Participants were then tested to determine whether the remaining four equivalence relations were acquired without teaching. Half of the children were taught naming responses first, then selecting responses. Half were taught in the reverse order. Results: Five out of 10 participants with ASD demonstrated the emergence of all four untaught relations. The remaining five participants showed variability. Nine of the 10 typically developing children demonstrated emergence of all untaught relations. Variation in teaching conditions had no significant effect on outcomes. Conclusions: Many children with ASD are capable of generalising to untaught equivalence relations. The results fail to support the claim that acquisition of naming responses is a pre-requisite for the emergence of untaught equivalence relations.
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14. Antshel K. {{Autism traits may be more prevalent in ADHD than previously reported}}. {Evid Based Ment Health}. 2014.
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15. Webb SJ. {{Multiple neonatal factors associated with autism spectrum disorders in infants}}. {Evid Based Ment Health}. 2014.
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16. Naushad SM, Jain JM, Prasad CK, Naik U, Akella RR. {{Autistic children exhibit distinct plasma amino acid profile}}. {Indian J Biochem Biophys}. 2013; 50(5): 474-8.
In order to ascertain whether autistic children display characteristic metabolic signatures that are of diagnostic value, plasma amino acid analyses were carried out on a cohort of 138 autistic children and 138 normal controls using reverse-phase HPLC. Pre-column derivatization of amino acids with phenyl isothiocyanate forms phenyl thio-carbamate derivates that have a lamba(max) of 254 nm, enabling their detection using photodiode array. Autistic children showed elevated levels of glutamic acid (120 +/- 89 vs. 83 +/- 35 micromol/L) and asparagine (85 +/- 37 vs. 47 +/- 19 micromol/L); lower levels of phenylalanine (45 +/- 20 vs. 59 +/- 18 micromol/L), tryptophan (24 +/- 11 vs. 41 +/- 16 micromol/L), methionine (22 +/- 9 vs. 28 +/- 9 micromol/L) and histidine (45 +/- 21 vs. 58 +/- 15 micromol/L). A low molar ratio of (tryptophan/large neutral amino acids) x 100 was observed in autism (5.4 vs 9.2), indicating lesser availability of tryptophan for neurotransmitter serotonin synthesis. To conclude, elevated levels of excitatory amino acids (glutamate and asparagine), decreased essential amino acids (phenylalanine, tryptophan and methionine) and decreased precursors of neurotransmitters (tyrosine and tryptophan) are the distinct characteristics of plasma amino acid profile of autistic children. Thus, such metabolic signatures might be useful tools for early diagnosis of autism.
17. Camargo SP, Rispoli M, Ganz J, Hong ER, Davis H, Mason R. {{A Review of the Quality of Behaviorally-Based Intervention Research to Improve Social Interaction Skills of Children with ASD in Inclusive Settings}}. {J Autism Dev Disord}. 2014.
Students with autism spectrum disorders (ASDs) often have difficulties in social interaction skills, which may prevent their successful inclusion in general education placements. Behaviorally-based social skills interventions have been shown to be effective in attenuating such difficulties in these environments. In light of the increasing number of children with ASD being educated in inclusive settings and requirements for the use of research-based interventions in schools, this paper (1) analyzes the quality of single-case research using behaviorally-based interventions to improve social interaction skills of children with ASD in inclusive settings and (2) evaluates whether such interventions can be considered an evidence-based practice. Characteristics and components of the interventions are summarized, and their implications for practice and future research are discussed.
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18. Goddard L, Dritschel B, Howlin P. {{A Preliminary Study of Gender Differences in Autobiographical Memory in Children with an Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2014.
Autobiographical memory was assessed in 24 children (12 male, 12 female, aged between 8 and 16 years) with autism spectrum disorder (ASD) and a comparison group of 24 typically developing (TD) children matched for age, IQ, gender and receptive language. Results suggested that a deficit in specific memory retrieval in the ASD group was more characteristic of male participants. Females in both the TD and ASD groups generated more detailed and emotional memories than males. They also demonstrated superior verbal fluency scores; verbal fluency and autobiographical memory cueing task performance were significantly positively correlated in females. Results are discussed in light of recent research suggesting gender differences in the phenotype of ASD.
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19. Gordon I, Pierce MD, Bartlett MS, Tanaka JW. {{Training Facial Expression Production in Children on the Autism Spectrum}}. {J Autism Dev Disord}. 2014.
Children with autism spectrum disorder (ASD) show deficits in their ability to produce facial expressions. In this study, a group of children with ASD and IQ-matched, typically developing (TD) children were trained to produce « happy » and « angry » expressions with the FaceMaze computer game. FaceMaze uses an automated computer recognition system that analyzes the child’s facial expression in real time. Before and after playing the Angry and Happy versions of FaceMaze, children posed « happy » and « angry » expressions. Naive raters judged the post-FaceMaze « happy » and « angry » expressions of the ASD group as higher in quality than their pre-FaceMaze productions. Moreover, the post-game expressions of the ASD group were rated as equal in quality as the expressions of the TD group.
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20. Mari-Bauset S, Zazpe I, Mari-Sanchis A, Llopis-Gonzalez A, Morales-Suarez-Varela M. {{Evidence of the Gluten-Free and Casein-Free Diet in Autism Spectrum Disorders: A Systematic Review}}. {J Child Neurol}. 2014.
In autism spectrum disorders, many parents resort to alternative treatments and these are generally perceived as risk free. Among these, the most commonly used is the gluten-free, casein-free diet. The objective of this work was to conduct a systematic review of studies published from 1970 to date related to the gluten-free, casein-free diet in autism spectrum disorder patients. Few studies can be regarded as providing sound scientific evidence since they were blinded randomized controlled trials, and even these were based on small sample sizes, reducing their validity. We observed that the evidence on this topic is currently limited and weak. We recommend that it should be only used after the diagnosis of an intolerance or allergy to foods containing the allergens excluded in gluten-free, casein-free diets. Future research should be based on this type of design, but with larger sample sizes.
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21. Peters SU, Gordon RL, Key AP. {{Induced Gamma Oscillations Differentiate Familiar and Novel Voices in Children With MECP2 Duplication and Rett Syndromes}}. {J Child Neurol}. 2014.
Normal levels of the methyl CpG-binding protein 2 (MeCP2) are critical to neurologic functioning, and slight alterations result in intellectual disability and autistic features. It was hypothesized that children with MECP2 duplication (overexpression of MeCP2) and Rett syndrome (underexpression of MeCP2) would exhibit distinct electroencephalographic (EEG) indices of auditory stimulus discrimination. In this study, gamma-band oscillatory responses to familiar and novel voices were examined and related to social functioning in 17 children (3-11 years old) with MECP2 duplication (n = 12) and Rett syndrome (n = 5). Relative to the stranger’s voice, gamma activity in response to the mother’s voice was increased in MECP2 duplication but decreased in Rett syndrome. In MECP2 duplication, greater mother versus stranger differences in gamma activity were associated with higher social functioning. For the first time, brain responses in a passive voice discrimination paradigm show that overexpression and underexpression of MeCP2 have differential effects on cortical information processing.
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22. Wijetunge LS, Angibaud J, Frick A, Kind PC, Nagerl UV. {{Stimulated Emission Depletion (STED) Microscopy Reveals Nanoscale Defects in the Developmental Trajectory of Dendritic Spine Morphogenesis in a Mouse Model of Fragile X Syndrome}}. {J Neurosci}. 2014; 34(18): 6405-12.
Dendritic spines are basic units of neuronal information processing and their structure is closely reflected in their function. Defects in synaptic development are common in neurodevelopmental disorders, making detailed knowledge of age-dependent changes in spine morphology essential for understanding disease mechanisms. However, little is known about the functionally important fine-morphological structures, such as spine necks, due to the limited spatial resolution of conventional light microscopy. Using stimulated emission depletion microscopy (STED), we examined spine morphology at the nanoscale during normal development in mice, and tested the hypothesis that it is impaired in a mouse model of fragile X syndrome (FXS). In contrast to common belief, we find that, in normal development, spine heads become smaller, while their necks become wider and shorter, indicating that synapse compartmentalization decreases substantially with age. In the mouse model of FXS, this developmental trajectory is largely intact, with only subtle differences that are dependent on age and brain region. Together, our findings challenge current dogmas of both normal spine development as well as spine dysgenesis in FXS, highlighting the importance of super-resolution imaging approaches for elucidating structure-function relationships of dendritic spines.
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23. McCarthy SE, Gillis J, Kramer M, Lihm J, Yoon S, Berstein Y, Mistry M, Pavlidis P, Solomon R, Ghiban E, Antoniou E, Kelleher E, O’Brien C, Donohoe G, Gill M, Morris DW, McCombie WR, Corvin A. {{De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability}}. {Mol Psychiatry}. 2014.
Schizophrenia is a serious psychiatric disorder with a broadly undiscovered genetic etiology. Recent studies of de novo mutations (DNMs) in schizophrenia and autism have reinforced the hypothesis that rare genetic variation contributes to risk. We carried out exome sequencing on 57 trios with sporadic or familial schizophrenia. In sporadic trios, we observed a ~3.5-fold increase in the proportion of nonsense DNMs (0.101 vs 0.031, empirical P=0.01, Benjamini-Hochberg-corrected P=0.044). These mutations were significantly more likely to occur in genes with highly ranked probabilities of haploinsufficiency (P=0.0029, corrected P=0.006). DNMs of potential functional consequence were also found to occur in genes predicted to be less tolerant to rare variation (P=2.01 x 10-5, corrected P=2.1 x 10-3). Genes with DNMs overlapped with genes implicated in autism (for example, AUTS2, CHD8 and MECP2) and intellectual disability (for example, HUWE1 and TRAPPC9), supporting a shared genetic etiology between these disorders. Functionally CHD8, MECP2 and HUWE1 converge on epigenetic regulation of transcription suggesting that this may be an important risk mechanism. Our results were consistent in an analysis of additional exome-based sequencing studies of other neurodevelopmental disorders. These findings suggest that perturbations in genes, which function in the epigenetic regulation of brain development and cognition, could have a central role in the susceptibility to, pathogenesis and treatment of mental disorders.Molecular Psychiatry advance online publication, 29 April 2014; doi:10.1038/mp.2014.29.
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24. Goffin D, Brodkin ES, Blendy JA, Siegel SJ, Zhou Z. {{Cellular origins of auditory event-related potential deficits in Rett syndrome}}. {Nat Neurosci}. 2014.
Dysfunction in sensory information processing is a hallmark of many neurological disorders, including autism spectrum disorders, schizophrenia and Rett syndrome (RTT). Using mouse models of RTT, a monogenic disorder caused by mutations in MECP2, we found that the large-scale loss of MeCP2 from forebrain GABAergic interneurons led to deficits in auditory event-related potentials and seizure manifestation, whereas the restoration of MeCP2 in specific classes of interneurons ameliorated these deficits.
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25. Wong LM, Goodrich-Hunsaker NJ, McLennan Y, Tassone F, Zhang M, Rivera SM, Simon TJ. {{Eye movements reveal impaired inhibitory control in adult male fragile x premutation carriers asymptomatic for fxtas}}. {Neuropsychology}. 2014.
Objective: Fragile X premutation carriers (fXPCs) have an expansion of 55 -200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance. Method: Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks. Results: Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII. Conclusion: Antisaccades require inhibitory control to inhibit reflexive eye movements. We found that eye movements are sensitive to impaired inhibitory control in fXPCs asymptomatic for FXTAS. Thus, eye movements may be useful in assessing FXTAS risk or disease progression. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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26. McElhanon BO, McCracken C, Karpen S, Sharp WG. {{Gastrointestinal Symptoms in Autism Spectrum Disorder: A Meta-analysis}}. {Pediatrics}. 2014.
BACKGROUND: In pediatric settings, parents often raise concerns about possible gastrointestinal (GI) symptoms in autism spectrum disorder (ASD), yet the specificity of these concerns are not well studied. OBJECTIVE: To conduct a meta-analysis of research investigating GI symptoms among children with ASD. METHODS: We searched Medline, PsycINFO, and PubMed databases (1980-2012) in peer-reviewed journals. Analysis involved studies with a comparison group presenting quantitative data on GI symptoms using combinations of terms for ASD and GI indicators. The systematic search yielded 15 studies. We calculated effect sizes and 95% confidence intervals (CIs) using a random-effects model. RESULTS: Children with ASD experience significantly more general GI symptoms than comparison groups, with a standardized mean difference of 0.82 (0.24) and a corresponding odds ratio (OR) of 4.42 (95% CI, 1.90-10.28). Analysis also indicated higher rates of diarrhea (OR, 3.63; 95% CI, 1.82-7.23), constipation (OR, 3.86; 95% CI, 2.23-6.71), and abdominal pain (OR, 2.45; 95% CI, 1.19-5.07). CONCLUSIONS: Results indicate greater prevalence of GI symptoms among children with ASD compared with control children. Identified studies involved high methodological variability and lack of comprehensive data prohibited analysis of GI pathophysiologies (eg, gastroesophageal reflux) typically associated with organic etiologies, limiting conclusions about the underpinnings of the observed association. Future research must address critical questions about the causes and long-term impact of GI symptoms in ASD. Such analyses will require more systematic research and clinical activities, including improved diagnostic screening, standardized assessment, and exploration of potential moderators (eg, dietary restrictions).
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27. Pineda JA, Carrasco K, Datko M, Pillen S, Schalles M. {{Neurofeedback training produces normalization in behavioural and electrophysiological measures of high-functioning autism}}. {Philos Trans R Soc Lond B Biol Sci}. 2014; 369(1644): 20130183.
Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting impairments in behaviour, social and communication skills. These deficits may arise from aberrant functional connections that impact synchronization and effective neural communication. Neurofeedback training (NFT), based on operant conditioning of the electroencephalogram (EEG), has shown promise in addressing abnormalities in functional and structural connectivity. We tested the efficacy of NFT in reducing symptoms in children with ASD by targeting training to the mirror neuron system (MNS) via modulation of EEG mu rhythms. The human MNS has provided a neurobiological substrate for understanding concepts in social cognition relevant to behavioural and cognitive deficits observed in ASD. Furthermore, mu rhythms resemble MNS phenomenology supporting the argument that they are linked to perception and action. Thirty hours of NFT on ASD and typically developing (TD) children were assessed. Both groups completed an eyes-open/-closed EEG session as well as a mu suppression index assessment before and after training. Parents filled out pre- and post-behavioural questionnaires. The results showed improvements in ASD subjects but not in TDs. This suggests that induction of neuroplastic changes via NFT can normalize dysfunctional mirroring networks in children with autism, but the benefits are different for TD brains.
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28. Vivanti G, Rogers SJ. {{Autism and the mirror neuron system: insights from learning and teaching}}. {Philos Trans R Soc Lond B Biol Sci}. 2014; 369(1644): 20130184.
Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others’ behaviour, (ii) the motivation to attend to and model conspecifics and (iii) the flexible and selective use of social learning. These factors are key targets of the Early Start Denver Model, an autism treatment approach which emphasizes social imitation, dyadic engagement, verbal and non-verbal communication and affect sharing. Analysis of the developmental processes and treatment-related changes in these different aspects of social learning in autism can shed light on the nature of the neuropsychological mechanisms underlying social learning and positive treatment outcomes in autism. This knowledge in turn may assist in developing more successful pedagogic approaches to autism spectrum disorder. Thus, intervention research can inform the debate on relations among neuropsychology of social learning, the role of the MNS, and educational practice in autism.
