1. Baldwin S, Costley D, Warren A. {{Employment Activities and Experiences of Adults with High-Functioning Autism and Asperger’s Disorder}}. {J Autism Dev Disord};2014 (Apr 9)
There is limited large-scale empirical research into the working lives of adults who have an autism spectrum disorder with no co-occurring intellectual disability. Drawing on data from a national survey, this report describes the employment activities and experiences of 130 adults with Asperger’s Disorder (AD) and high functioning autism (HFA) in Australia. Outcome measures include current occupation; occupational skill level and alignment with educational attainment; type of job contract; hours of work; support received to find work; support received in the workplace; and positive and negative experiences of employment. The findings confirm and expand upon existing evidence that adults with AD and HFA, despite their capacity and willingness to work, face significant disadvantages in the labour market and a lack of understanding and support in employment settings.
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2. Baudouin SJ. {{Heterogeneity and convergence: the synaptic pathophysiology of autism}}. {Eur J Neurosci};2014 (Apr);39(7):1107-1113.
Autism is a developmental disorder characterised by a high heterogeneity of clinical diagnoses and genetic associations. This heterogeneity is a challenge for the identification of the pathophysiology of the disease and for the development of new therapeutic strategies. New conceptual approaches are being used to try to challenge this complexity and gene cluster analysis studies suggest that the pathophysiology of autism is associated with a dysregulation of specific cellular mechanisms. This review will present the experimental evidence for a convergence of synaptic pathophysiology between syndromic and non-syndromic forms of autism, grouped under the generic term of autism spectrum disorders. In particular I will highlight the results from genetic mouse models identifying a convergence of dysregulation of the synaptic type I metabotropic glutamate receptor pathway in mouse models for autism spectrum disorders. These results help to build a new conceptual framework for the study of the synaptic phenotype of autism, which is important for the identification of new therapeutic strategies.
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3. Boda B, Mendez P, Boury-Jamot B, Magara F, Muller D. {{Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome}}. {Eur J Neurosci};2014 (Apr);39(7):1130-1137.
Fragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, and results from the silencing of the FMR1 gene coding for a protein implicated in the regulation of protein synthesis at synapses. The lack of functional Fragile X mental retardation protein has been proposed to result in an excessive signaling of synaptic metabotropic glutamate receptors, leading to alterations of synapse maturation and plasticity. It remains, however, unclear how mechanisms of activity-dependent spine dynamics are affected in Fmr knockout (Fmr1-KO) mice and whether they can be reversed. Here we used a repetitive imaging approach in hippocampal slice cultures to investigate properties of structural plasticity and their modulation by signaling pathways. We found that basal spine turnover was significantly reduced in Fmr1-KO mice, but markedly enhanced by activity. Additionally, activity-mediated spine stabilization was lost in Fmr1-KO mice. Application of the metabotropic glutamate receptor antagonist alpha-Methyl-4-carboxyphenylglycine (MCPG) enhanced basal turnover, improved spine stability, but failed to reinstate activity-mediated spine stabilization. In contrast, enhancing phosphoinositide-3 kinase (PI3K) signaling, a pathway implicated in various aspects of synaptic plasticity, reversed both basal turnover and activity-mediated spine stabilization. It also restored defective long-term potentiation mechanisms in slices and improved reversal learning in Fmr1-KO mice. These results suggest that modulation of PI3K signaling could contribute to improve the cognitive deficits associated with FXS.
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4. Correia CT, Conceicao IC, Oliveira B, Coelho J, Sousa I, Sequeira AF, Almeida J, Cafe C, Duque F, Mouga S, Roberts W, Gao K, Lowe JK, Thiruvahindrapuram B, Walker S, Marshall CR, Pinto D, Nurnberger JI, Scherer SW, Geschwind DH, Oliveira G, Vicente AM. {{Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders}}. {Mol Autism};2014 (Apr 10);5(1):28.
BACKGROUND: Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study. METHODS: From the AGP CNV genomic screen in 2,147 ASD individuals, we selected for characterization an ANXA1 gene duplication that was absent in 4,964 population-based controls. We further screened the duplication in a follow-up sample including 1,496 patients and 410 controls, and evaluated clinical correlations and family segregation. Sequencing of exonic/downstream ANXA1 regions was performed in 490 ASD patients for identification of additional variants. RESULTS: The ANXA1 duplication, overlapping the last four exons and 3’UTR region, had an overall prevalence of 11/3,643 (0.30%) in unrelated ASD patients but was not identified in 5,374 controls. Duplication carriers presented no distinctive clinical phenotype. Family analysis showed neuropsychiatric deficits and ASD traits in multiple relatives carrying the duplication, suggestive of a complex genetic inheritance. Sequencing of exonic regions and the 3’UTR identified 11 novel changes, but no obvious variants with clinical significance. CONCLUSIONS: We provide multilevel evidence for a role of ANXA1 in ASD etiology. Given its important role as mediator of glucocorticoid function in a wide variety of brain processes, including neuroprotection, apoptosis, and control of the neuroendocrine system, the results add ANXA1 to the growing list of rare candidate genetic etiological factors for ASD.
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5. Elamin NE, Al-Ayadhi LY. {{Brain autoantibodies in autism spectrum disorder}}. {Biomark Med};2014 (Mar);8(3):345-352.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in reciprocal social interactions as well as restricted, repetitive and stereotyped patterns of behavior. The etiology of ASD is not well understood, although many factors have been associated with its pathogenesis, such genetic, neurological, environmental and immunological factors. Several studies have reported the production of numerous autoantibodies that react with specific brain proteins and brain tissues in autistic children and alter the function of the attacked brains tissue. In addition, the potential role of maternal autoantibodies to the fatal brain in the etiology of some cases of autism has also been reported. Identification and understanding of the role of brain autoantibodies as biological biomarkers may allow earlier detection of ASD, lead to a better understanding of the pathogenesis of ASD and have important therapeutic implications.
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6. Engineer CT, Centanni TM, Im KW, Rahebi KC, Buell EP, Kilgard MP. {{Degraded speech sound processing in a rat model of fragile X syndrome}}. {Brain Res};2014 (Apr 5)
Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. Although auditory cortex responses are known to be abnormal in fragile X syndrome, it is not clear how these differences impact speech sound processing. This study provides the first evidence that the cortical representation of speech sounds is impaired in Fmr1 knockout rats, despite normal speech discrimination behavior. Evoked potentials and spiking activity in response to speech sounds, noise burst trains, and tones were significantly degraded in primary auditory cortex, anterior auditory field and the ventral auditory field. Neurometric analysis of speech evoked activity using a pattern classifier confirmed that activity in these fields contains significantly less information about speech sound identity in Fmr1 knockout rats compared to control rats. Responses were normal in the posterior auditory field, which is associated with sound localization. The greatest impairment was observed in the ventral auditory field, which is related to emotional regulation. Dysfunction in the ventral auditory field may contribute to poor emotional regulation in fragile X syndrome and may help explain the observation that later auditory evoked responses are more disturbed in fragile X syndrome compared to earlier responses. Rodent models of fragile X syndrome are likely to prove useful for understanding the biological basis of fragile X syndrome and for testing candidate therapies.
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7. Frye RE, James SJ. {{Metabolic pathology of autism in relation to redox metabolism}}. {Biomark Med};2014 (Mar);8(3):321-330.
An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorder (ASD). Glutathione synthesis and intracellular redox balance are linked to folate and methylation metabolism, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct ASD endophenotype that is closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Biomarkers that reflect these metabolic abnormalities will be discussed in the context of an ASD metabolic endophenotype that may lead to a better understanding of the pathophysiological mechanisms underlying core and associated ASD symptoms. Last, we discuss how these biomarkers have been used to guide the development of novel ASD treatments.
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8. Itahashi T, Yamada T, Watanabe H, Nakamura M, Jimbo D, Shioda S, Toriizuka K, Kato N, Hashimoto R. {{Altered network topologies and hub organization in adults with autism: a resting-state FMRI study}}. {PLoS One};2014;9(4):e94115.
Recent functional magnetic resonance imaging (fMRI) studies on autism spectrum condition (ASC) have identified dysfunctions in specific brain networks involved in social and non-social cognition that persist into adulthood. Although increasing numbers of fMRI studies have revealed atypical functional connectivity in the adult ASC brain, such functional alterations at the network level have not yet been fully characterized within the recently developed graph-theoretical framework. Here, we applied a graph-theoretical analysis to resting-state fMRI data acquired from 46 adults with ASC and 46 age- and gender-matched controls, to investigate the topological properties and organization of autistic brain network. Analyses of global metrics revealed that, relative to the controls, participants with ASC exhibited significant decreases in clustering coefficient and characteristic path length, indicating a shift towards randomized organization. Furthermore, analyses of local metrics revealed a significantly altered organization of the hub nodes in ASC, as shown by analyses of hub disruption indices using multiple local metrics and by a loss of « hubness » in several nodes (e.g., the bilateral superior temporal sulcus, right dorsolateral prefrontal cortex, and precuneus) that are critical for social and non-social cognitive functions. In particular, local metrics of the anterior cingulate cortex consistently showed significant negative correlations with the Autism-Spectrum Quotient score. Our results demonstrate altered patterns of global and local topological properties that may underlie impaired social and non-social cognition in ASC.
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9. Laugeson EA, Ellingsen R, Sanderson J, Tucci L, Bates S. {{The ABC’s of Teaching Social Skills to Adolescents with Autism Spectrum Disorder in the Classroom: The UCLA PEERS Program}}. {J Autism Dev Disord};2014 (Apr 9)
Social skills training is a common treatment method for adolescents with autism spectrum disorder (ASD), yet very few evidence-based interventions exist to improve social skills for high-functioning adolescents on the spectrum, and even fewer studies have examined the effectiveness of teaching social skills in the classroom. This study examines change in social functioning for adolescents with high-functioning ASD following the implementation of a school-based, teacher-facilitated social skills intervention known as Program for the Education and Enrichment of Relational Skills (PEERS (R) ). Seventy-three middle school students with ASD along with their parents and teachers participated in the study. Participants were assigned to the PEERS (R) treatment condition or an alternative social skills curriculum. Instruction was provided daily by classroom teachers and teacher aides for 14-weeks. Results reveal that in comparison to an active treatment control group, participants in the PEERS (R) treatment group significantly improved in social functioning in the areas of teacher-reported social responsiveness, social communication, social motivation, social awareness, and decreased autistic mannerisms, with a trend toward improved social cognition on the Social Responsiveness Scale. Adolescent self-reports indicate significant improvement in social skills knowledge and frequency of hosted and invited get-togethers with friends, and parent-reports suggest a decrease in teen social anxiety on the Social Anxiety Scale at a trend level. This research represents one of the few teacher-facilitated treatment intervention studies demonstrating effectiveness in improving the social skills of adolescents with ASD in the classroom: arguably the most natural social setting of all.
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10. Richa S, Fahed M, Khoury E, Mishara B. {{Suicide in Autism Spectrum Disorders}}. {Arch Suicide Res};2014 (Apr 8)
Introduction: This review focuses on suicide in patients with Autism Spectrum Disorders (ASD) as well as risk factors and comorbidities persons with ASD who have attempted suicide. Material and Methods: Research in PubMed and Psychinfo for articles. Results: Suicide in ASD is largely understudied. Although suicide is common is clinical samples, we have little knowledge of suicide in persons with ASD in the general population. Comorbidity, particularly with depression and other affective disorders or schizoid disorders and psychotic symptoms is often reported, so it is difficult to determine if suicidality is associated with ASD or the comorbid disorder. Clinical samples suggest that suicide occurs more frequently in high functioning autism. Physical and sexual abuse, bullying and changes in routine are precipitating events associated with suicide risk. Conclusion: Persons with ASD present risk factors inherent to their diagnosis (deficit in expression of feelings and thoughts), along with risk factors pertaining to the general population (abuse, depression, anxiety, etc … ). The inability of persons with PDD to express emotions and thoughts makes the diagnosis of suicidal ideation difficult and demands important adjustments to traditional psychotherapeutic interventions. More research is needed to determine the incidence of suicidal behaviors in persons with ASD, to identify risk and protective factors, as well as to assess the effectiveness of prevention strategies and interventions.
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11. Rojas DC, Wilson LB. {{gamma-band abnormalities as markers of autism spectrum disorders}}. {Biomark Med};2014 (Mar);8(3):353-368.
Autism is a behaviorally diagnosed neurodevelopmental disorder with no current biomarkers with high specificity and sensitivity. gamma-band abnormalities have been reported in many studies of autism spectrum disorders. gamma-band activity is associated with perceptual and cognitive functions that are compromised in autism. Some gamma-band deficits have also been seen in unaffected first-degree relatives, suggesting heritability of these findings. This review covers the published literature on gamma abnormalities in autism, the proposed mechanisms underlying the deficits and the potential for translation into new treatments. Although the utility of gamma-band metrics as diagnostic biomarkers is currently limited, such changes in autism are also useful as endophenotypes, for evaluating potential neural mechanisms, and for use as surrogate markers of treatment response to interventions.
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12. Schwartz CE. {{Aberrant tryptophan metabolism: the unifying biochemical basis for autism spectrum disorders?}}. {Biomark Med};2014 (Mar);8(3):313-315.
« …it is quite possible that impairment of the metabolism of tryptophan … provides the unifying model that explains the heterogeneity of autism spectrum disorder… »
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13. Steinman G, Mankuta D. {{Umbilical cord biomarkers in autism determination}}. {Biomark Med};2014 (Mar);8(3):317-319.
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14. Tinker J, Carbone PS, Viskochil D, Mathiesen A, Ma KN, Stevenson DA. {{Screening children with neurofibromatosis type 1 for autism spectrum disorder}}. {Am J Med Genet A};2014 (Apr 8)
Autism spectrum disorder (ASD) is reported to be increased in neurofibromatosis type 1 (NF1), but it’s unknown if ASD screening tools are sensitive and specific for NF1. This study compared the rate at which children with NF1 screen-positive for two ASD screening tools [Modified Checklist for Autism in Toddlers (M-CHAT) and Childhood Autism Spectrum Test (CAST)] to the screen-positive rate of the general population. A retrospective cross-sectional observational design to investigate the association between children with NF1 and at risk status for ASD was used. Medical records of children between 16 months and 11 years of age seen in an NF Clinic were reviewed for an ASD screening questionnaire. There were no statistically significant differences in the screen-positive rate for ASD in NF1 compared to published controls, but mean CAST scores were higher in NF1. (c) 2014 Wiley Periodicals, Inc.
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15. Wang L, Conlon MA, Christophersen CT, Sorich MJ, Angley MT. {{Gastrointestinal microbiota and metabolite biomarkers in children with autism spectrum disorders}}. {Biomark Med};2014 (Mar);8(3):331-344.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Many affected individuals also display symptoms of gastrointestinal (GI) disturbance, suggesting GI factors may play an important role in the pathogenesis of ASD and/or related complications. The current review will focus on evidence supporting a role for the GI microbiota and their fermentation products in the etiology and/or symptoms of ASD, and their potential use as biomarkers. GI-related biomarkers could potentially enable early identification of ASD at risk of GI disturbance, and thereby guide targeted interventions, potentially improving the health and quality of life of affected individuals.
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16. Warreyn P, Van der Paelt S, Roeyers H. {{Social-communicative abilities as treatment goals for preschool children with autism spectrum disorder: the importance of imitation, joint attention, and play}}. {Dev Med Child Neurol};2014 (Apr 9)
Autism spectrum disorder (ASD) is a pervasive developmental disorder with a lifelong impact on multiple domains of functioning. Often, a diagnosis is possible by 3 years of age. Given the benefits of early intervention, it is advisable to start treatment as soon as possible after the diagnosis has been made. Among other factors, early intervention should focus on social-communicative abilities such as imitation, joint attention, and play. In this review, the typical developmental course and functions of these social-communicative abilities are described, and the problems young children with ASD experience in this domain. In addition, different approaches to promoting these abilities are explained. The authors recommend the inclusion of imitation, joint attention, and play as treatment goals in community settings for children with ASD.
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17. Wilson H. {{Potential biomarkers of autism}}. {Biomark Med};2014 (Mar);8(3):311-312.
