1. De Rubeis S, Buxbaum JD. {{Recent advances in the genetics of autism spectrum disorder}}. {Current neurology and neuroscience reports}. 2015 Jun;15(6):553.
Autism spectrum disorder (ASD) is a devastating neurodevelopmental disorder with high prevalence in the population and a pronounced male preponderance. ASD has a strong genetic basis, but until recently, a large fraction of the genetic factors contributing to liability was still unknown. Over the past 3 years, high-throughput next-generation sequencing on large cohorts has exposed a heterogeneous and complex genetic landscape and has revealed novel risk genes. Here, we provide an overview of the recent advances on the ASD genetic architecture, with an emphasis on the estimates of heritability, the contribution of common variants, and the role of inherited and de novo rare variation. We also examine the genetic components of the reported gender bias. Finally, we discuss the emerging findings from sequencing studies and how they illuminate crucial aspects of ASD pathophysiology.
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2. Du RY, Yiu CC, Wong VC, McGrath CP. {{Autism Developmental Profiles and Cooperation with Oral Health Screening}}. {J Autism Dev Disord}. 2015 May 7.
To determine the associations between autism developmental profiles and cooperation with an oral health screening among preschool children with autism spectrum disorders (ASDs). A random sample of Special Child Care Centres registered with the Government Social Welfare Department in Hong Kong was selected (19 out of 37 Centres). All preschool children with ASDs were invited to participate in the oral health survey and 347 children agreed to participate (among 515 invited). A checklist of autism developmental profiles: (1) level of cognitive functioning, (2) social skills development, (3) communication skills development, (4) reading skills and (5) challenging behaviours was ascertained. Feasibility of conducting oral health screening in preschool children with ASDs was associated with their cognitive functioning (p = 0.001), social skills development (p = 0.002), communication skills development (p < 0.001), reading skills (p < 0.001) and challenging behaviours (p = 0.06). In regression analyses accounting for age (in months) and gender, inability to cooperate with an oral health screening was associated with high level of challenging behaviours (OR 10.50, 95 % CI 2.89-38.08, p < 0.001) and reduced cognitive functioning (OR 5.29, 95 % CI 1.14-24.61, p = 0.034). Age (in months) was positively associated with likelihood of cooperative behaviour with an oral health screening (OR 1.06, 95 % CI 1.03, 1.08, p < 0.001). Feasibility of conducting population-wide oral health screening among preschool children with ASDs is associated with their developmental profiles; and in particular levels of cognitive functioning, and challenging behaviours.
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3. Fisher KM, Peterson JD, Albert JD. {{Identifying state resources and support programs on e-government websites for persons with intellectual and developmental disabilities}}. {Nursing research and practice}. 2015;2015:127638.
This descriptive cross-sectional study identified resources and programs that are available nationwide on the Internet to support individuals and families with intellectual and developmental disabilities (I/DD), with a focus on intellectual disability. This evaluation included easily identifiable information on specific resources and highlighted unique programs found in individual states that were linked from e-government websites. Researchers documented the ease of access and available information for all 50 states and the District of Columbia. A number of disparities and areas for improvement were recorded for states and I/DD websites. The researchers conclude that a number of additional health and support services will be needed to address the growing needs of this vulnerable population.
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4. Gdalyahu A, Lazaro M, Penagarikano O, Golshani P, Trachtenberg JT, Gescwind DH. {{The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2) Stabilizes New Spines: An In Vivo Mouse Study}}. {PloS one}. 2015;10(5):e0125633.
The establishment and maintenance of neuronal circuits depends on tight regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein associated with autism, would play a key role in this process. Indeed, we found that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates, but failed to stabilize. Notably, rates of spine elimination were unaltered, suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry.
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5. Gozes I. {{The cytoskeleton as a drug target for neuroprotection: the case of the autism-mutated ADNP}}. {Biological chemistry}. 2015 May 8.
15 years ago we discovered activity-dependent neuroprotective protein (ADNP), and showed that it is essential for brain formation/ function. Our protein interaction studies identified ADNP as a member of the chromatin remodelling complex, SWI/SNF also associated with alternative splicing of tau and prediction of tauopathy. Recently, we have identified cytoplasmic ADNP interactions with the autophagy regulating microtubule-associated protein 1 light chain 3 (LC3) and with microtubule end binding (EB) proteins. The ADNPEB- binding SIP domain is shared with the ADNP snippet drug candidate, NAPVSIPQ termed NAP (davunetide). Thus, we identified a precise target for ADNP/NAP (davunetide) neuroprotection toward improved drug development.
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6. Hanley M, Riby DM, Carty C, Melaugh McAteer A, Kennedy A, McPhillips M. {{The use of eye-tracking to explore social difficulties in cognitively able students with autism spectrum disorder: A pilot investigation}}. {Autism : the international journal of research and practice}. 2015 May 6.
Individuals with autism spectrum disorder do not just ‘grow out of’ their early difficulties in understanding the social world. Even for those who are cognitively able, autism-related difficulties continue into adulthood. Atypicalities attending to and interpreting communicative signals from others can provide barriers to success in education, employment and relationships. In the current study, we use eye-tracking during real social interaction to explore attention to social cues (e.g. face, eyes, mouth) and links to social awareness in a group of cognitively able University students with autism spectrum disorder and typically developing students from the same University. During the interaction, students with autism spectrum disorder showed less eye fixation and more mouth fixation than typically developing students. Importantly, while 63% of typically developing participants reported thinking they were deceived about the true nature of the interaction, only 9% of autism spectrum disorder participants picked up this subtle social signal. We argue that understanding how these social attentional and social awareness difficulties manifest during adulthood is important given the growing number of adults with autism spectrum disorder who are attending higher level education. These adults may be particularly susceptible to drop-out due to demands of coping in situations where social awareness is so important.
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7. Harrop C, Gulsrud A, Shih W, Hovsepyan L, Kasari C. {{Characterizing caregiver responses to restricted and repetitive behaviors in toddlers with autism spectrum disorder}}. {Autism : the international journal of research and practice}. 2015 May 6.
Restricted and repetitive behaviors are a core feature of autism spectrum disorder. This descriptive study documented the presence of restricted and repetitive behaviors in 85 toddlers with autism spectrum disorder as they interacted with their caregiver in a play interaction. For each child restricted and repetitive behavior, a caregiver response/non-response was coded. Caregiver responses were rated as successful or unsuccessful. In all, 83 toddlers demonstrated at least one restricted and repetitive behavior in 10 min. The most common child restricted and repetitive behavior was repetitive object use with 72 children displaying at least one instance of this category of restricted and repetitive behavior. Overall, caregivers responded to fewer than half of their child’s restricted and repetitive behaviors, and caregiver response varied by child restricted and repetitive behavior type. The most common response was redirection. Success varied by child restricted and repetitive behavior type and caregiver response-redirections were most successful for child verbal and motor restricted and repetitive behaviors, whereas physical or verbal responses were rated more successful for repetitive object use and visual restricted and repetitive behaviors. This study represents the first attempt to characterize how caregivers respond to restricted and repetitive behaviors. Toddlers with autism spectrum disorder are already demonstrating a variety of restricted and repetitive behaviors within the context of a free play sessions, and caregivers differentially and naturally respond to them.
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8. Ifrim MF, Williams KR, Bassell GJ. {{Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome}}. {The Journal of neuroscience : the official journal of the Society for Neuroscience}. 2015 May 6;35(18):7116-30.
Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3’UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3’UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS.
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9. Keen D, Webster A, Ridley G. {{How well are children with autism spectrum disorder doing academically at school? An overview of the literature}}. {Autism : the international journal of research and practice}. 2015 May 6.
The academic achievement of individuals with autism spectrum disorder has received little attention from researchers despite the importance placed on this by schools, families and students with autism spectrum disorder. Investigating factors that lead to increased academic achievement thus would appear to be very important. A review of the literature was conducted to identify factors related to the academic achievement of children and adolescents with autism spectrum disorder. A total of 19 studies were identified that met the inclusion criteria for the review. Results indicated that many individuals demonstrate specific areas of strength and weakness and there is a great deal of variability in general academic achievement across the autism spectrum. Adolescents and individuals with lower IQ scores were underrepresented, and few studies focused on environmental factors related to academic success. The importance of individualised assessments that profile the relative strengths and weaknesses of children and adolescents to aid in educational programming was highlighted. Further research on child-related and environmental factors that predict academic achievement is needed.
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10. Manning C, Tibber MS, Charman T, Dakin SC, Pellicano E. {{Enhanced integration of motion information in children with autism}}. {The Journal of neuroscience : the official journal of the Society for Neuroscience}. 2015 May 6;35(18):6979-86.
To judge the overall direction of a shoal of fish or a crowd of people, observers must integrate motion signals across space and time. The limits on our ability to pool motion have largely been established using the motion coherence paradigm, in which observers report the direction of coherently moving dots amid randomly moving noise dots. Poor performance by autistic individuals on this task has widely been interpreted as evidence of disrupted integrative processes. Critically, however, motion coherence thresholds are not necessarily limited only by pooling. They could also be limited by imprecision in estimating the direction of individual elements or by difficulties segregating signal from noise. Here, 33 children with autism 6-13 years of age and 33 age- and ability-matched typical children performed a more robust task reporting mean dot direction both in the presence and the absence of directional variability alongside a standard motion coherence task. Children with autism were just as sensitive to directional differences as typical children when all elements moved in the same direction (no variability). However, remarkably, children with autism were more sensitive to the average direction in the presence of directional variability, providing the first evidence of enhanced motion integration in autism. Despite this improved averaging ability, children with autism performed comparably to typical children in the motion coherence task, suggesting that their motion coherence thresholds may be limited by reduced segregation of signal from noise. Although potentially advantageous under some conditions, increased integration may lead to feelings of « sensory overload » in children with autism.
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11. Mohammadzaheri F, Koegel LK, Rezaei M, Bakhshi E. {{A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT) and Adult-Driven Applied Behavior Analysis (ABA) Intervention on Disruptive Behaviors in Public School Children with Autism}}. {J Autism Dev Disord}. 2015 May 8.
Children with autism often demonstrate disruptive behaviors during demanding teaching tasks. Language intervention can be particularly difficult as it involves social and communicative areas, which are challenging for this population. The purpose of this study was to compare two intervention conditions, a naturalistic approach, Pivotal Response Treatment (PRT) with an adult-directed ABA approach on disruptive behavior during language intervention in the public schools. A randomized clinical trial design was used with two groups of children, matched according to age, sex and mean length of utterance. The data showed that the children demonstrated significantly lower levels of disruptive behavior during the PRT condition. The results are discussed with respect to antecedent manipulations that may be helpful in reducing disruptive behavior.
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12. Pozo P, Sarria E. {{Still stressed but feeling better: Well-being in autism spectrum disorder families as children become adults}}. {Autism : the international journal of research and practice}. 2015 May 8.
The transition to adulthood and adulthood itself have been identified as times of stress for parents of individuals with autism spectrum disorder. Longitudinal studies, however, show improvements in the well-being of mothers of adolescents and young adults with autism spectrum disorder. This article presents a cross-sectional study of 102 Spanish parents (51 mothers and 51 fathers) of 102 individuals with autism spectrum disorder. The aim was to examine parental well-being (evaluated based on stress, anxiety, depression and psychological well-being) in three groups of parents of adults, adolescents and young children with autism spectrum disorder. In addition, the relationships between parental well-being and the characteristics of their children, social support, parental age and sense of coherence were analysed. The results showed that although parental stress and psychological well-being levels were similar across the groups, depression and anxiety were lower in parents of adolescents or adults compared with parents of young children. Different factors predicted different measures of parental well-being, but sense of coherence emerged as the main predictive factor for all parental well-being measures. These findings are discussed in relation to parental adaptation over the lifespan and the implications for interventions in autism spectrum disorder families.
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13. Serret S, Thummler S, Dor E, Vesperini S, Santos A, Askenazy F. {{Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports}}. {BMC psychiatry}. 2015 May 7;15(1):107.
BACKGROUND: Phelan-Mc Dermid syndrome is a contiguous disorder resulting from 22q13.3 deletion implicating the SHANK3 gene. The typical phenotype includes neonatal hypotonia, moderate to severe intellectual disability, absent or delayed speech, minor dysmorphic features and autism or autistic-like behaviour. Recently, point mutations or micro-deletions of the SHANK3 gene have been identified, accompanied by a phenotype different from the initial clinically description in Phelan McDermid syndrome. CASE PRESENTATION: Here we present two case studies with similar psychiatric and genetic diagnosis as well as similar clinical history and evolution. The two patients were diagnosed with autism spectrum disorders in childhood and presented regression with catatonia features and behavioural disorders after a stressful event during adolescence. Interestingly, both patients presented mutation/microdeletion of the SHANK3 gene, inducing a premature stop codon in exon 21. Different pharmacological treatments (antipsychotics, benzodiazepines, mood stabilizer drugs, antidepressants, and methylphenidate) failed to improve clinical symptoms and lead to multiple adverse events. In contrast, lithium therapy reversed clinical regression, stabilized behavioural symptoms and allowed patients to recover their pre-catatonia level of functioning, without significant side effects. CONCLUSION: These cases support the hypothesis of a specific SHANK3 phenotype. This phenotype might be linked to catatonia-like deterioration for which lithium use could be an efficient treatment. Therefore, these cases provide an important contribution to the field of autism research, clinical genetics and possible pharmacological answers.
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14. Stahmer AC, Pellecchia M. {{Moving towards a more ecologically valid model of parent-implemented interventions in autism}}. {Autism : the international journal of research and practice}. 2015 Apr;19(3):259-61.
15. Tint A, Weiss JA. {{Family wellbeing of individuals with autism spectrum disorder: A scoping review}}. {Autism : the international journal of research and practice}. 2015 May 6.
Families play an important role in supporting individuals with autism spectrum disorder across the lifespan. Indicators of family wellbeing can help to establish benchmarks for service provision and evaluation; however, a critical first step is a clear understanding of the construct in question. The purpose of the current scoping review was to (a) summarize current conceptualizations and measurements of family wellbeing, (b) synthesize key findings, and (c) highlight gaps and limitations in the extant literature. A final review of 86 articles highlighted the difficulty of synthesizing findings of family wellbeing in the autism spectrum disorder literature due to varied measurement techniques and the limited use of a common theoretical direction. Considerations for future research are presented with an eye toward policy relevance.
