1. Aggarwal S, Angus B. {{Misdiagnosis versus missed diagnosis: diagnosing autism spectrum disorder in adolescents}}. {Australas Psychiatry};2015 (Feb 4)
OBJECTIVE: The diagnosis of children with autism spectrum disorders (ASDs) is sometimes delayed until adolescence. This study tries to identify the symptoms in clients that initiated a referral to an autism team of an early intervention service providing psychiatric care for young people between the ages of 15 and 25 and who subsequently receive a new diagnosis of autism. METHODS: Thirty-one ASD assessments were carried out during a period of 3 years in an early intervention service in Australia. An attempt to identify the common presenting symptoms and trends in the referrals for ASD assessment within the service was made. RESULTS: Most common presentation of adolescents getting referred for ASD assessment was with depressive symptoms followed by mixed anxiety and depression and primary psychotic symptoms. There was a significant gender difference, with a higher number of males getting referred for ASD assessment. CONCLUSION: ASDs can go undetected during childhood and these clients can sometimes present during adolescence to mental health services for a psychiatric comorbidity. Regular training opportunities for clinicians dealing with them could improve the chances of ASDs being picked up during their episode of care at an early intervention service, thus optimizing their management.
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2. Cusack JP, Williams JH, Neri P. {{Action perception is intact in autism spectrum disorder}}. {J Neurosci};2015 (Feb 4);35(5):1849-1857.
Autistic traits span a wide spectrum of behavioral departures from typical function. Despite the heterogeneous nature of autism spectrum disorder (ASD), there have been attempts at formulating unified theoretical accounts of the associated impairments in social cognition. A class of prominent theories capitalizes on the link between social interaction and visual perception: effective interaction with others often relies on discrimination of subtle nonverbal cues. It has been proposed that individuals with ASD may rely on poorer perceptual representations of other people’s actions as returned by dysfunctional visual circuitry and that this, in turn, may lead to less effective interpretation of those actions for social behavior. It remains unclear whether such perceptual deficits exist in ASD: the evidence currently available is limited to specific aspects of action recognition, and the reported deficits are often attributable to cognitive factors that may not be strictly visual (e.g., attention). We present results from an exhaustive set of measurements spanning the entire action processing hierarchy, from motion detection to action interpretation, designed to factor out effects that are not selectively relevant to this function. Our results demonstrate that the ASD perceptual system returns functionally intact signals for interpreting other people’s actions adequately; these signals can be accessed effectively when autistic individuals are prompted and motivated to do so under controlled conditions. However, they may fail to exploit them adequately during real-life social interactions.
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3. Djuric U, Cheung AY, Zhang W, Mok RS, Lai W, Piekna A, Hendry JA, Joel Ross P, Pasceri P, Kim DS, Salter MW, Ellis J. {{MECP2e1 isoform mutation affects the form and function of neurons derived from Rett syndrome patient iPS cells}}. {Neurobiol Dis};2015 (Jan 30)
MECP2 mutations cause the X-linked neurodevelopmental disorder Rett Syndrome (RTT) by consistently altering the protein encoded by the MECP2e1 alternative transcript. While mutations that simultaneously affect both MECP2e1 and MECP2e2 isoforms have been widely studied, the consequence of MECP2e1 deficiency on human neurons remains unknown. Here we report the first isoform-specific patient induced pluripotent stem cell (iPSC) model of RTT. RTTe1 patient iPS cell-derived neurons retain an inactive X-chromosome and express only the mutant allele. Single-cell mRNA analysis demonstrated they have a molecular signature of cortical neurons. Mutant neurons exhibited a decrease in soma size, reduced dendritic complexity and decreased cell capacitance, consistent with impaired neuronal maturation. The soma size phenotype was rescued cell-autonomously by MECP2e1 transduction in a level-dependent manner but not by MECP2e2 gene transfer. Importantly, MECP2e1 mutant neurons showed dysfunction in action potential generation, voltage-gated Na+ currents, and miniature excitatory synaptic current frequency and amplitude. We conclude that MECP2e1 mutation affects soma size, information encoding properties and synaptic connectivity in human neurons that are defective in RTT.
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4. Fairthorne J, Jacoby P, Bourke J, de Klerk N, Leonard H. {{Onset of maternal psychiatric disorders after the birth of a child with autism spectrum disorder: A retrospective cohort study}}. {Autism};2015 (Feb 4)
BACKGROUND: Mothers of a child with autism spectrum disorder have more psychiatric disorders after the birth of their child. This might be because they have more psychiatric disorders before the birth, or the increase could be related to the burden of caring for their child. AIMS: We aimed to calculate the incidence of a psychiatric diagnosis in women with no psychiatric history after the birth of their eldest child with autism spectrum disorder compared to women with no child with autism spectrum disorder or intellectual disability and no psychiatric history. METHODS: By linking datasets from Western Australian population-based registries, we calculated the incidence of a psychiatric disorder in mothers of children with autism spectrum disorder and compared to mothers of children with no autism spectrum disorder or intellectual disability. Negative binomial regression using STATA 13 was used for all analyses. RESULTS: Apart from alcohol and substance abuse, mothers of children with autism spectrum disorder had higher incidences of all categories of psychiatric disorders than other mothers. CONCLUSION AND IMPLICATIONS: The increase of psychiatric disorders in mothers of children with autism spectrum disorder and no psychiatric history compared to similar mothers with no child with autism spectrum disorder or intellectual disability might be due to a pre-existing genetic disposition coupled with an environmental trigger provided by the challenges of raising their children with autism spectrum disorder. In addition, the increased burden borne by the mothers of children with autism spectrum disorder might result in a higher incidence of psychiatric disorders in mothers who are not genetically disposed.
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5. Finke EH, Hickerson B, McLaughlin E. {{Parental intention to support video game play by children with autism spectrum disorder: An application of the Theory of Planned Behavior}}. {Lang Speech Hear Serv Sch};2015 (Feb 4)
Purpose: To determine parental attitudes regarding engagement with video games by their children with ASD and whether attitudes vary based on ASD symptom severity. Method: Online survey methodology was used to gather information from parents of children with ASD between the ages of 8 and 12 years old. The finalized dataset included 152 cases. Descriptive statistics and frequency analyses were used to examine participant demographics and video game play. Descriptive and inferential statistics were used to evaluate questions on the Theory of Planned Behavior. Regression analyses determined the predictive ability of the Theory of Planned Behavior constructs, and t-tests provided additional descriptive information about between-group differences. Results: Children with ASD play video games. There are no significant differences in the time, intensity or types of games played based on severity of ASD symptoms (mild vs. moderate). Parents of children with ASD had positive attitudes about video game play. Conclusions: Parents of children with ASD appear to support video game play. On average, parents indicated video game play was positive for their children with ASD, particularly if they believed the games were having a positive impact on their child’s development.
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6. Johnston SB, Raines RT. {{Conformational stability and catalytic activity of PTEN variants linked to cancers and autism spectrum disorders}}. {Biochemistry};2015 (Feb 3)
Phosphoinositides are membrane components that play critical regulatory roles in mammalian cells. The enzyme PTEN, which catalyzes the dephosphorylation of the phosphoinositide PIP3, is damaged in most sporadic tumors. Mutations in the PTEN gene have also been linked to autism spectrum disorders and other forms of delayed development. Here, human PTEN is shown to be on the cusp of unfolding under physiological conditions. Variants of human PTEN linked to somatic cancers and disorders on the autism spectrum are shown to be impaired in their conformational stability, catalytic activity, or both. Those variants linked only to autism have higher activity than those linked to cancers. PTEN-L, which is a secreted trans-active isoform, has greater conformational stability than does the wild-type enzyme. These data indicate that PTEN is a fragile enzyme cast in a crucial role in cellular metabolism.
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7. Kitagishi Y, Minami A, Nakanishi A, Ogura Y, Matsuda S. {{Neuron Membrane Trafficking and Protein Kinases Involved in Autism and ADHD}}. {Int J Mol Sci};2015;16(2):3095-3115.
A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1) are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD) is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT). AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention.
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8. Malishkevich A, Amram N, Hacohen-Kleiman G, Magen I, Giladi E, Gozes I. {{Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer’s pathologies}}. {Transl Psychiatry};2015;5:e501.
Activity-dependent neuroprotective protein (ADNP) is a most frequent autism spectrum disorder (ASD)-associated gene and the only protein significantly decreasing in the serum of Alzheimer’s disease (AD) patients. Is ADNP associated with ASD being more prevalent in boys and AD more prevalent in women? Our results revealed sex-related learning/memory differences in mice, reflecting hippocampal expression changes in ADNP and ADNP-controlled AD/ASD risk genes. Hippocampal ADNP transcript content was doubled in male vs female mice, with females showing equal expression to ADNP haploinsufficient (ADNP(+/)(-)) males and no significant genotype-associated reduction. Increased male ADNP expression was replicated in human postmortem hippocampal samples. The hippocampal transcript for apolipoprotein E (the major risk gene for AD) was doubled in female mice compared with males, and further doubled in the ADNP(+/-) females, contrasting a decrease in ADNP(+/-) males. Previously, overexpression of the eukaryotic translation initiation factor 4E (eIF4E) led to ASD-like phenotype in mice. Here, we identified binding sites on ADNP for eIF4E and co-immunoprecipitation. Furthermore, hippocampal eIF4E expression was specifically increased in young ADNP(+/-) male mice. Behaviorally, ADNP(+/-) male mice exhibited deficiencies in object recognition and social memory compared with ADNP(+/+) mice, while ADNP(+/-) females were partially spared. Contrasting males, which preferred novel over familiar mice, ADNP(+/+) females showed no preference to novel mice and ADNP(+/-) females did not prefer mice over object. ADNP expression, positioned as a master regulator of key ASD and AD risk genes, introduces a novel concept of hippocampal gene-regulated sexual dimorphism and an ADNP(+/-) animal model for translational psychiatry.
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9. Mosconi MW, Mohanty S, Greene RK, Cook EH, Vaillancourt DE, Sweeney JA. {{Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder}}. {J Neurosci};2015 (Feb 4);35(5):2015-2025.
Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD.
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10. Nemirovsky SI, Cordoba M, Zaiat JJ, Completa SP, Vega PA, Gonzalez-Moron D, Medina NM, Fabbro M, Romero S, Brun B, Revale S, Ogara MF, Pecci A, Marti M, Vazquez M, Turjanski A, Kauffman MA. {{Whole Genome Sequencing Reveals a De Novo SHANK3 Mutation in Familial Autism Spectrum Disorder}}. {PLoS One};2015;10(2):e0116358.
INTRODUCTION: Clinical genomics promise to be especially suitable for the study of etiologically heterogeneous conditions such as Autism Spectrum Disorder (ASD). Here we present three siblings with ASD where we evaluated the usefulness of Whole Genome Sequencing (WGS) for the diagnostic approach to ASD. METHODS: We identified a family segregating ASD in three siblings with an unidentified cause. We performed WGS in the three probands and used a state-of-the-art comprehensive bioinformatic analysis pipeline and prioritized the identified variants located in genes likely to be related to ASD. We validated the finding by Sanger sequencing in the probands and their parents. RESULTS: Three male siblings presented a syndrome characterized by severe intellectual disability, absence of language, autism spectrum symptoms and epilepsy with negative family history for mental retardation, language disorders, ASD or other psychiatric disorders. We found germline mosaicism for a heterozygous deletion of a cytosine in the exon 21 of the SHANK3 gene, resulting in a missense sequence of 5 codons followed by a premature stop codon (NM_033517:c.3259_3259delC, p.Ser1088Profs*6). CONCLUSIONS: We reported an infrequent form of familial ASD where WGS proved useful in the clinic. We identified a mutation in SHANK3 that underscores its relevance in Autism Spectrum Disorder.
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11. Papadopoulos N, Sciberras E, Hiscock H, Mulraney M, McGillivray J, Rinehart N. {{The Efficacy of a Brief Behavioral Sleep Intervention in School-Aged Children With ADHD and Comorbid Autism Spectrum Disorder}}. {J Atten Disord};2015 (Feb 2)
OBJECTIVE: Sleep problems are common in children with autism spectrum disorders (ASD) and ADHD and impact adversely on child and parent well-being. The study evaluated the efficacy of a brief behavioral sleep intervention in children with comorbid ADHD-ASD. METHOD: A subsample of children with ADHD-ASD (n = 61; 5-13 years; 89% male) participating in the Sleeping Sound With ADHD study were included in the current investigation. The subsample comprised of 28 children randomized to the sleep intervention group, while 33 were randomized to usual clinical care. The intervention consisted of two clinical consultations and a follow-up phone call covering sleep hygiene and standardized behavioral strategies. RESULTS: Children with ADHD-ASD who received the intervention had large improvements in sleep problems and moderate improvements in child behavioral functioning 3 and 6 months post-randomization. CONCLUSION: These findings suggest that a brief behavioral sleep intervention can improve sleep problems in children with ADHD-ASD.
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12. Parra MA, Cubelli R, Bellamy KJ, Abrahams S, Avila CL, Castro-Jaramillo LD, Della Sala S. {{Gist-based illusions within and across stimulus modalities in autism spectrum disorder}}. {Memory};2015 (Feb 4):1-11.
Some studies have reported a low rate of false recognition (FR) in individuals with autism spectrum disorder (ASD) relative to non-autistic comparison participants (CPs). This finding, however, has not always been replicated and the source of the discrepancy remains unknown. We hypothesised that poor episodic memory functions may account for this finding. We used an adapted version of the Deese, Roediger and McDermott paradigm which presents lists of words, pictures or word-picture pairs to obtain measures of performance which reflect episodic [hits and false alarms (FAs)] and semantic (FR) memory functions. Results showed a decreased rate of FR in ASD individuals with lists of words which rose above the rate seen in non-autistic CPs with lists of word-picture pairs. This increased rate of FR in ASD was accompanied by a parallel increase in hits and a decrease in FA which reached a similar level in the two groups. Poor episodic memory functions may prevent individuals with ASD from acquiring item information which in turn precludes the formation of semantic links between items. This could render them less prone to FR.
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13. Shield A, Meier RP, Tager-Flusberg H. {{The Use of Sign Language Pronouns by Native-Signing Children with Autism}}. {J Autism Dev Disord};2015 (Feb 3)
We report the first study on pronoun use by an under-studied research population, children with autism spectrum disorder (ASD) exposed to American Sign Language from birth by their deaf parents. Personal pronouns cause difficulties for hearing children with ASD, who sometimes reverse or avoid them. Unlike speech pronouns, sign pronouns are indexical points to self and other. Despite this transparency, we find evidence from an elicitation task and parental report that signing children with ASD avoid sign pronouns in favor of names. An analysis of spontaneous usage showed that all children demonstrated the ability to point, but only children with better-developed sign language produced pronouns. Differences in language abilities and self-representation may explain these phenomena in sign and speech.
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14. Sparaci L, Formica D, Lasorsa FR, Mazzone L, Valeri G, Vicari S. {{Untrivial Pursuit: Measuring Motor Procedures Learning in Children with Autism}}. {Autism Res};2015 (Jan 30)
Numerous studies have underscored prevalence of motor impairments in children with autism spectrum disorders (ASD), but only few of them have analyzed motor strategies exploited by ASD children when learning a new motor procedure. To evaluate motor procedure learning and performance strategies in both ASD and typically developing (TD) children, we built a virtual pursuit rotor (VPR) task, requiring tracking a moving target on a computer screen using a digitalized pen and tablet. Procedural learning was measured as increased time on target (TT) across blocks of trials on the same day and consolidation was assessed after a 24-hour rest. The program and the experimental setting (evaluated in a first experiment considering two groups of TD children) allowed also measures of continuous time on target (CTT), distance from target (DT) and distance from path (DP), as well as 2D reconstructions of children’s trajectories. Results showed that the VPR was harder for children with ASD than for TD controls matched for chronological age and intelligence quotient, but both groups displayed comparable motor procedure learning (i.e., similarly incremented their TT). However, closer analysis of CTT, DT, and DP as well as 2D trajectories, showed different motor performance strategies in ASD, highlighting difficulties in overall actions planning. Data underscore the need for deeper investigations of motor strategies exploited by children with ASD when learning a new motor procedure. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Thomeer ML, Smith RA, Lopata C, Volker MA, Lipinski AM, Rodgers JD, McDonald CA, Lee GK. {{Randomized Controlled Trial of Mind Reading and In Vivo Rehearsal for High-Functioning Children with ASD}}. {J Autism Dev Disord};2015 (Feb 3)
This randomized controlled trial evaluated the efficacy of a computer software (i.e., Mind Reading) and in vivo rehearsal treatment on the emotion decoding and encoding skills, autism symptoms, and social skills of 43 children, ages 7-12 years with high-functioning autism spectrum disorder (HFASD). Children in treatment (n = 22) received the manualized protocol over 12 weeks. Primary analyses indicated significantly better posttest performance for the treatment group (compared to controls) on 3 of the 4 measures of emotion decoding and encoding and these were maintained at 5-week follow-up. Analyses of secondary measures favored the treatment group for 1 of the 2 measures; specifically, ASD symptoms were significantly lower at posttest and follow-up.
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16. Thompson JI, Peck CE, Karvelas G, Hartwell CA, Guarnaccia C, Brown A, Crewther DP. {{Temporal processing as a source of altered visual perception in high autistic tendency}}. {Neuropsychologia};2015 (Jan 30)
Superior local at the expense of global perception characterises vision in autism spectrum disorders (ASD). However, progress towards discovering a neural mechanism has been slow. Here we used known differences in magnocellular and parvocellular receptive field properties to assess the temporal encoding of information, via flicker fusion paradigms, in those high and low in self-reported autistic tendency (Autism Spectrum Quotient – AQ). A Low AQ group (AQ</=13, n=22), and a High AQ group (AQ>/=18, n=17) undertook a 4AFC luminance flicker fusion (FF) with 5 temporal contrasts from 5% to 100%, and a 2AFC isoluminant red-green colour fusion task. Both groups showed an increase in fusion thresholds with temporal achromatic contrast. The High AQ group displayed diminished flicker fusion thresholds compared to the Low AQ at the lowest contrasts. For the red-green colour fusion task, the High AQ group displayed mean fusion frequency slightly greater than the Low AQ group. A significant interaction between 5% luminance contrast and the red-green fusion frequencies demonstrated that the differences in thresholds were not simply due to variations in overall attentional capacity between groups. These differences in flicker fusion thresholds are in accordance with reported differences in cortical visual evoked potential nonlinearities, particularly relating to the neural efficiency of the magnocellular pathway.
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17. Vohra R, Madhavan S, Khanna R, Becker-Cottrill B. {{Child’s autism severity: effect on West Virginia caregiver satisfaction with school services}}. {W V Med J};2014 (Sep-Oct);110(5):32-39.
Survey data was collected from 301 primary caregivers of children with autism registered at West Virginia Autism Training Center (WV ATC), to examine the impact of child’s autism severity on caregiver satisfaction with school services. Satisfaction with six school services was measured via a 3-point Likert scale: speech-language therapy, occupational therapy, social skills training, physical therapy, behavioral interventions, and assistance in improving study skills. Ordinal logistic regressions showed that caregivers of children with high autism severity were less likely to be satisfied with school services, as compared to caregivers of children with low autism severity (OR’s from 0.45 to 0.39). No significant differences existed in caregiver satisfaction with services between high and low autism severity groups, after addition of caregiver burden to the model. Findings suggest that child’s autism severity is a significant predictor of caregiver satisfaction with school services, and should be considered during development of child’s Individualized Education Program(IEP) and evaluation of caregiver satisfaction with the IEP.
18. Xu W, Fu Z, Wang J, Zhang Y. {{RELATIONSHIP BETWEEN AUTISTIC TRAITS AND HOARDING IN A LARGE NON-CLINICAL CHINESE SAMPLE: MEDIATING EFFECT OF ANXIETY AND DEPRESSION}}. {Psychol Rep};2015 (Feb 4)
Summary.-Researchers and clinical practitioners have found that hoarding appears in many autism patients and that most of these patients show high anxiety and depression. There is no consensus on the relationship between autistic traits and hoarding, and little research concerning the role of negative emotions. This study investigated the relationship between autistic traits and hoarding in a large non-clinical Chinese sample. Participants were 3,229 university students (M age = 20.5 yr., SD = 1.6; 1,839 men) who were recruited in classroom. They completed measures of hoarding, autistic symptomology, anxiety, and depression: specifically the Saving Inventory-Revised, the Autism-Spectrum Quotient, the Zung Self-Rating Anxiety Scale, and The Center for Epidemiological Studies Depression Scale. Mediating effects of anxiety and depression in the correlation between autistic traits and hoarding were also explored. There was a weak but significant correlation between autistic traits and hoarding. Significant mediating effects of anxiety and depression were observed. Hoarding in people with high autistic traits could be influenced by anxiety and depression.
