1. Baez S, Rattazzi A, Gonzalez-Gadea ML, Torralva T, Vigliecca NS, Decety J, Manes F, Ibanez A. {{Integrating intention and context: assessing social cognition in adults with Asperger syndrome}}. {Front Hum Neurosci};2012;6:302.
Deficits in social cognition are an evident clinical feature of the Asperger syndrome (AS). Although many daily life problems of adults with AS are related to social cognition impairments, few studies have conducted comprehensive research in this area. The current study examined multiple domains of social cognition in adults with AS assessing the executive functions (EF) and exploring the intra and inter-individual variability. Fifteen adult’s diagnosed with AS and 15 matched healthy controls completed a battery of social cognition tasks. This battery included measures of emotion recognition, theory of mind (ToM), empathy, moral judgment, social norms knowledge, and self-monitoring behavior in social settings. We controlled for the effect of EF and explored the individual variability. The results indicated that adults with AS had a fundamental deficit in several domains of social cognition. We also found high variability in the social cognition tasks. In these tasks, AS participants obtained mostly subnormal performance. EF did not seem to play a major role in the social cognition impairments. Our results suggest that adults with AS present a pattern of social cognition deficits characterized by the decreased ability to implicitly encode and integrate contextual information in order to access to the social meaning. Nevertheless, when social information is explicitly presented or the situation can be navigated with abstract rules, performance is improved. Our findings have implications for the diagnosis and treatment of individuals with AS as well as for the neurocognitive models of this syndrome.
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2. Berryer MH, Hamdan FF, Klitten LL, Moller RS, Carmant L, Schwartzentruber J, Patry L, Dobrzeniecka S, Rochefort D, Neugnot M, Lacaille JC, Niu Z, Eng CM, Yang Y, Palardy S, Belhumeur C, Rouleau GA, Tommerup N, Immken L, Beauchamp MH, Patel GS, Majewski J, Tarnopolsky MA, Scheffzek K, Hjalgrim H, Michaud JL, Di Cristo G. {{Mutations in SYNGAP1 Cause Intellectual Disability, Autism and a Specific form of Epilepsy by Inducing Haploinsufficiency}}. {Hum Mutat};2012 (Nov 15)
De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP-activating protein, cause non-syndromic intellectual disability (NSID). All disease-causing point mutations identified until now in SYNGAP1 are truncating, raising the possibility of an association between this type of mutations and NSID. Here, we report the identification of the first pathogenic missense mutations (c.1084T>C [p.W362R]; c.1685C>T [p.P562L]) and three novel truncating mutations (c.283dupC [p.H95PfsX5]; c.2212_2213del [p.S738X]; (c.2184del [p.N729TfsX31]) in SYNGAP1 in patients with NSID. A subset of these patients also showed ataxia, autism, and a specific form of generalized epilepsy that can be refractory to treatment. All of these mutations occurred de novo, except c.283dupC, which was inherited from a father who is a mosaic. Biolistic transfection of wild-type SYNGAP1 in pyramidal cells from cortical organotypic cultures significantly reduced activity-dependent pERK levels. In contrast, constructs expressing p.W362R, p.P562L or the previously described p.R579X had no significant effect on pERK levels. These experiments suggest that the de novo missense mutations, p.R579X, and possibly all the other truncating mutations in SYNGAP1 result in a loss of its function. Moreover, our study confirms the involvement of SYNGAP1 in autism while providing novel insight into the epileptic manifestations associated with its disruption.
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3. Boyle CA, Cordero JF, Trevathan E. {{The national center on birth defects and developmental disabilities: past, present, and future}}. {Am J Prev Med};2012 (Dec);43(6):655-658.
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4. Corbett BA, Schupp CW, Lanni KE. {{Comparing biobehavioral profiles across two social stress paradigms in children with and without autism spectrum disorders}}. {Mol Autism};2012 (Nov 17);3(1):13.
ABSTRACT: BACKGROUND: Autism spectrum disorders (ASD) are defined by impairment in reciprocal social interaction and flexible adaptation to the environment. This study compared physiological stress in children with and without ASD exposed to two social stress protocols. We hypothesized that the ASD group would show heightened initial and enduring cortisol levels to the social stressors, which would be moderated by age and intelligence. METHODS: Twenty-seven children with ASD and 32 with typical development (TYP) completed a standardized social-evaluative performance task and a validated paradigm of social play with peers. Physiological stress was measured by salivary cortisol at nine time points. Statistical approaches included repeated-measures linear mixed models and correlation analyses. RESULTS: The average cortisol level of both groups during initial exposure to social situations was significantly greater than baseline levels (ASD, P = 0.018; TYP, P = 0.006). Stress responsivity was significantly different between the groups; the TYP group showed a significant reduction in cortisol over time (P = 0.023), whereas the ASD group maintained an elevated cortisol level (P >0.05). The ASD group evidenced greater variability in between-group, within-group and intra-individual analyses. Age was a positive moderator of stress for the ASD group (P = 0.047), whereas IQ was a negative moderator for the TYP group (P = 0.061). CONCLUSIONS: Initial stress to novel social scenarios is idiosyncratic and predictive of subsequent exposure. Amidst significant variability in cortisol, children with ASD show enhanced and sustained social stress that increases with age. Developmental and cognitive factors differentially moderate stress in children with ASD and TYP, respectively. A model of neuroendocrine reactivity is proposed.
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5. Enticott PG, Oberman LM. {{Synaptic plasticity and non-invasive brain stimulation in autism spectrum disorders}}. {Dev Med Child Neurol};2012 (Nov 15)
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6. Gurkan CK, Hagerman RJ. {{TARGETED TREATMENTS IN AUTISM AND FRAGILE X SYNDROME}}. {Res Autism Spectr Disord};2012 (Oct 1);6(4):1311-1320.
Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted as highly heritable, there is no genetic cure at this time. Autism is shown to be linked to several genes and is a feature of some complex genetic disorders, including fragile X syndrome (FXS), fragile X premutation involvement, tuberous sclerosis and Rett syndrome. The term autism spectrum disorders (ASDs) covers autism, Asperger syndrome and pervasive developmental disorders (PDD-NOS) and the etiologies are heterogeneous. In recent years, targeted treatments have been developed for several disorders that have a known specific genetic cause leading to autism. Since there are significant molecular and neurobiological overlaps among disorders, targeted treatments developed for a specific disorder may be helpful in ASD of unknown etiology. Examples of this are two drug classes developed to treat FXS, Arbaclofen, a GABA(B) agonist, and mGluR5 antagonists, and both may be helpful in autism without FXS. The mGluR5 antagonists are also likely to have a benefit in the aging problems of fragile X premutation carriers, the fragile X -associated tremor ataxia syndrome (FXTAS) and the Parkinsonism that can occur in aging patients with fragile X syndrome. Targeted treatments in FXS which has a well known genetic etiology may lead to new targeted treatments in autism.
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7. Halbach NS, Smeets EE, Steinbusch C, Maaskant MA, van Waardenburg D, Curfs LM. {{Aging in Rett syndrome: a longitudinal study}}. {Clin Genet};2012 (Nov 20)
BACKGROUND: Little is known about the aging process of people with specific syndromes, like Rett syndrome (RTT). Recognition of the clinical and behavioral characteristics of the adult RTT is needed in order to improve future management of the RTT girl and counseling of parents. METHODS: In association with the Dutch RTT parent association, a five-year longitudinal study was carried out. The study population consisted of 53 adult women with a clinical diagnosis of RTT. Postal questionnaires were sent, including demographic features, skills, physical and psychiatric morbidity. RESULTS: At the time of the second measurement seven women had died. In 2012 80% of the questionnaires (37/46) were returned. Mean age of the women was 31.4 years. Molecular confirmation was possible for 83% of the women for whom analyses were carried out. The adult RTT woman has a more or less stable condition. The general disorder profile is that of a slow on-going deterioration of gross motor functioning in contrast to a better preserved cognitive functioning, less autonomic and epileptic features and good general health. CONCLUSIONS: This is the first longitudinal cohort study about aging in RTT. Continuing longitudinal studies are needed to gain more insight into the aging process in RTT.
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8. Johnson BP, Rinehart NJ, Papadopoulos N, Tonge B, Millist L, White O, Fielding J. {{A closer look at visually guided saccades in autism and Asperger’s disorder}}. {Front Integr Neurosci};2012;6:99.
Motor impairments have been found to be a significant clinical feature associated with autism and Asperger’s disorder (AD) in addition to core symptoms of communication and social cognition deficits. Motor deficits in high-functioning autism (HFA) and AD may differentiate these disorders, particularly with respect to the role of the cerebellum in motor functioning. Current neuroimaging and behavioral evidence suggests greater disruption of the cerebellum in HFA than AD. Investigations of ocular motor functioning have previously been used in clinical populations to assess the integrity of the cerebellar networks, through examination of saccade accuracy and the integrity of saccade dynamics. Previous investigations of visually guided saccades in HFA and AD have only assessed basic saccade metrics, such as latency, amplitude, and gain, as well as peak velocity. We used a simple visually guided saccade paradigm to further characterize the profile of visually guided saccade metrics and dynamics in HFA and AD. It was found that children with HFA, but not AD, were more inaccurate across both small (5 degrees ) and large (10 degrees ) target amplitudes, and final eye position was hypometric at 10 degrees . These findings suggest greater functional disturbance of the cerebellum in HFA than AD, and suggest fundamental difficulties with visual error monitoring in HFA.
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9. Jung NH, Janzarik WG, Delvendahl I, Munchau A, Biscaldi M, Mainberger F, Baumer T, Rauh R, Mall V. {{Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome}}. {Dev Med Child Neurol};2012 (Nov 15)
Aim We aimed to investigate the induction of long-term potentiation (LTP)-like plasticity by paired associative stimulation (PAS) in patients with high-functioning autism and Asperger syndrome (HFA/AS). Method PAS with an interstimulus interval between electrical and transcranial magnetic stimulation of 25 ms (PAS(25) ) was performed in patients with HFA/AS (n=9; eight males, one female; mean age 17y 11mo, SD 4y 5mo) and in typically developing age-matched volunteers (n=9; five males, four females; mean age 22y 4mo, SD 5y 2mo). The amplitude of motor-evoked potentials was measured before PAS(25) , immediately after stimulation, and 30 minutes and 60 minutes later. A PAS protocol adapted to individual N20 latency (PAS(N20+2) ) was performed in six additional patients with HFA/AS. Short-interval intracortical inhibition was measured using paired-pulse stimulation. Results In contrast to the typically developing participants, the patients with HFA/AS did not show a significant increase in motor-evoked potentials after PAS(25) . This finding could also be demonstrated after adaptation for N20 latency. Short-interval intracortical inhibition of patients with HFA/AS was normal compared with the comparison group and did not correlate with PAS effect. Interpretation Our results show a significant impairment of LTP-like plasticity induced by PAS in individuals with HFA/AS compared with typically developing participants. This finding is in accordance with results from animal studies as well as human studies. Impaired LTP-like plasticity in patients with HFA/AS points towards reduced excitatory synaptic connectivity and deficits in sensory-motor integration in these patients.
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10. Jung S, Sainato DM. {{Teaching play skills to young children with autism}}. {J Intellect Dev Disabil};2012 (Nov 16)
Background Play is critical for the development of young children and is an important part of their daily routine. However, children with autism often exhibit deficits in play skills and engage in stereotypic behaviour. We reviewed studies to identify effective instructional strategies for teaching play skills to young children with autism. Method Empirical studies on teaching play skills to young children with autism published from 1990 to 2011 were located. These studies included single subject and group designs. Results Twenty-six studies were reviewed. The majority of studies on teaching play skills used combined interventions. Children with autism improved their play skills, with direct intervention embedding their interests during play. Improvements in play skills increased positive social interactions and decreased inappropriate behaviour as collateral effects. Conclusions Further research is needed to develop more effective play skill interventions that assess the functional use of play and are implemented in the natural environment.
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11. Maurer MH. {{Genomic and proteomic advances in autism research}}. {Electrophoresis};2012 (Sep 19)
Recent studies suggest that adult neural stem cells (NSCs) may play a role in the pathogenesis of a number of the developmental disorders subsumed under the term autism spectrum disorders (ASD) that have in common impaired social interaction, communication deficits, and stereotypical behavior or interests. Since there is no « unifying hypothesis » about the etiology and pathogenesis of ASD, several factors have been associated with ASD, including genetic factors, physical co-morbidity, disturbances of brain structure and function, biochemical anomalies, cognitive impairment, and disorders of speech and emotional development, mostly the lack of empathy. Most of disturbances of brain interconnectivity are regarded as main problem in autism. Since NSCs have a distinct life cycle in the mammalian brain consisting of proliferation, migration, arborization, integration into existing neuronal circuits, and myelinization, disturbances in NSCs differentiation is thought to be deleterious. In the current review, I will summarize the results of genomic and proteomic studies finding susceptibility genes and proteins for autism with regard to NSCs differentiation and maturation.
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12. Megargel E, Broder-Fingert S. {{Autism and hospitals: a difficult match}}. {Acad Pediatr};2012 (Nov);12(6):469-470.
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13. O’Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, Carvill G, Kumar A, Lee C, Ankenman K, Munson J, Hiatt JB, Turner EH, Levy R, O’Day DR, Krumm N, Coe BP, Martin BK, Borenstein E, Nickerson DA, Mefford HC, Doherty D, Akey JM, Bernier R, Eichler EE, Shendure J. {{Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders}}. {Science};2012 (Nov 15)
Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations, but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or disrupt splicing. We estimate that recurrent disruptive mutations in six genes-CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1-may contribute to 1% of sporadic ASDs. Our data support associations between specific genes and reciprocal subphenotypes (CHD8-macrocephaly, DYRK1A-microcephaly) and replicate the importance of a beta-catenin/chromatin remodeling network to ASD etiology.
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14. Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, Lupski JR, Ramocki MB. {{The Behavioral Phenotype in MECP2 Duplication Syndrome: A Comparison With Idiopathic Autism}}. {Autism Res};2012 (Nov 20)
Alterations in the X-linked gene MECP2 encoding the methyl-CpG-binding protein 2 have been linked to autism spectrum disorders (ASDs). Most recently, data suggest that overexpression of MECP2 may be related to ASD. To better characterize the relevance of MECP2 overexpression to ASD-related behaviors, we compared the core symptoms of ASD in MECP2 duplication syndrome to nonverbal mental age-matched boys with idiopathic ASD. Within the MECP2 duplication group, we further delineated aspects of the behavioral phenotype and also examined how duplication size and gene content corresponded to clinical severity. We compared ten males with MECP2 duplication syndrome (ages 3-10) with a chronological and mental age-matched sample of nine nonverbal males with idiopathic ASD. Our results indicate that boys with MECP2 duplication syndrome share the core behavioral features of ASD (e.g. social affect, restricted/repetitive behaviors). Direct comparisons of ASD profiles revealed that a majority of boys with MECP2 duplication syndrome are similar to idiopathic ASD; they have impairments in social affect (albeit to a lesser degree than idiopathic ASD) and similar severity in restricted/repetitive behaviors. Nonverbal mental age did not correlate with severity of social impairment or repetitive behaviors. Within the MECP2 duplication group, breakpoint size does not predict differences in clinical severity. In addition to social withdrawal and stereotyped behaviors, we also found that hyposensitivity to pain/temperature are part of the behavioral phenotype of MECP2 duplication syndrome. Our results illustrate that overexpression/increased dosage of MECP2 is related to core features of ASD. Autism Res 2012, : -. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Robledo J, Donnellan AM, Strandt-Conroy K. {{An exploration of sensory and movement differences from the perspective of individuals with autism}}. {Front Integr Neurosci};2012;6:107.
Parents, teachers, and people who themselves experience sensory and movement differences have consistently reported disturbances of sensation and movement associated with autism. Our review of the literature has revealed both historical and recent references to and research about sensory and movement difference characteristics and symptoms for individuals with autism. What is notably infrequent in this literature, however, is research that highlights the perspective of the individual with autism. If we wish to truly understand the experience of sensory and movement differences for individuals with autism, we must explore their experiences and perspectives. This study presents a qualitative analysis of more than 40 h in-depth inquiry into the lives of five individuals with the autism label. Data were sorted into six categories: perception, action, posture, emotion, communication, and cognition. The insights into sensory and movement differences and autism offered by these individuals was illuminating. We found that the data strongly supported the presence of disruption of organization and regulation of sensory and movement differences in the lived experience of these participants with autism. The present data suggests that in autism this disruption of organization and regulation is amplified in terms of quantity, quality, intensity, and may affect everyday life. These data contribute to a more expansive view of autism that incorporates the possibility that autism is a disorder that affects motor planning, behavior, communication, the sensory motor system, and the dynamic interaction of all of these.
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16. Sadakata T, Shinoda Y, Oka M, Sekine Y, Furuichi T. {{Autistic-like behavioral phenotypes in a mouse model with copy number variation of the CAPS2/CADPS2 gene}}. {FEBS Lett};2012 (Nov 14)
Ca(2+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) facilitates secretion and trafficking of dense-core vesicles. Recent genome-wide association studies of autism have identified several microdeletions due to copy number variation (CNV) in one of the chromosome 7q31.32 alleles on which the locus for CAPS2 is located in autistic patients. To evaluate the biological significance of reducing CAPS2 copy number, we analyzed CAPS2 heterozygous mice. Our present findings suggest that adequate levels of CAPS2 protein are critical for normal brain development and behavior, and that allelic changes due to CNV may contribute to autistic symptoms in combination with deficits in other autism-associated genes.
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17. Taylor MJ, Charman T, Robinson EB, Plomin R, Happe F, Asherson P, Ronald A. {{Developmental associations between traits of autism spectrum disorder and attention deficit hyperactivity disorder: a genetically informative, longitudinal twin study}}. {Psychol Med};2012 (Nov 16):1-12.
BACKGROUND: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and associated subclinical traits, regularly co-occur with one another. However, the aetiology of their co-occurrence remains poorly understood. This paper provides the first genetically informative, longitudinal analysis of the interaction between traits of ASD and ADHD, and explores their genetic and environmental overlap. Method Parents of approximately 5000 twin pairs completed questionnaires assessing traits of ASD and ADHD when twins were aged 8 and 12 years. Cross-lagged longitudinal modelling explored their developmental association, enabling a consideration of phenotypic-driven processes. Overlapping aetiological influences on traits at age 12 years were explored using bivariate twin modelling. RESULTS: Traits of ADHD at age 8 years were more strongly predictive of traits of ASD at 12 years than traits of ASD at 8 years were of traits of ADHD at 12 years. Analysis of traits by subscales assessing specific symptom domains suggested that communication difficulties were most strongly associated with traits of ADHD. Bivariate modelling suggested moderate genetic overlap on traits in males (genetic correlation = 0.41), and a modest degree of overlap in females (genetic correlation = 0.23) at age 12 years. CONCLUSIONS: Traits of ADHD at age 8 years significantly influence traits of ASD at age 12 years, after controlling for their initial relationship at age 8 years. In particular, early ADHD traits influenced later communication difficulties. These findings demonstrate the dynamic nature of co-occurring traits across development. In addition, these findings add to a growing body of literature suggesting that traits of ASD and ADHD may arise via similar aetiological processes.
