1. Anand N, Agrawal A, Burger EL, Ferrero E, Fogelson JL, Kaito T, LaGrone MO, Le Huec JC, Lee JH, Mudiyam R, Sasao Y, Sembrano JN, Trobisch PD, Yang SH. {{The Prevalence of the Use of MIS Techniques in the Treatment of Adult Spinal Deformity (ASD) Amongst Members of the Scoliosis Research Society (SRS) in 2016}}. {Spine deformity}. 2019; 7(2): 319-24.
STUDY DESIGN: Electronic survey administered to Scoliosis Research Society members. OBJECTIVE: To determine the prevalence of minimally invasive surgery (MIS) techniques for the treatment of adult spinal deformity. SUMMARY OF BACKGROUND DATA: There is a paucity of data available on the practice pattern, prevalence of minimally invasive spine surgery, and the preferred minimally invasive techniques in the treatment of adult spine deformity. METHODS: An electronic nine-question survey regarding individual usage pattern of minimally invasive spine surgery techniques was administered in 2016 to the members of the Scoliosis Research Society. Determinants included complexity in condition of patient population, prevalence of use of minimally invasive techniques in the surgeon’s practice, prevalence of use of a particular MIS technique, strategy elected during surgery, adoption of staging of procedures and timing between staging of procedures. RESULTS: A total of 357 surgeons responded (61.3% response rate), and 154 (43.1%) of the respondents said that they use MIS as a part of their surgical treatment of adult spinal deformity. However, of these 154 respondents, 67 (43.5%) said that their MIS usage in deformity practice was between 1% and 20%. Only 11 (7.2%) said that they used MIS 81% to 100% of the time. The top MIS approaches that surgeons chose were MIS lateral lumbar interbody fusion 109 (70.59%) and MIS percutaneous screws 91 (58.8%). CONCLUSIONS: The low rate of adoption of these techniques among the SRS members may be due to the false perception that there is not enough data to support that MIS techniques are better. This and the fact that a practitioner needs to be facile at different MIS techniques may be the true impediment to the adoption of MIS techniques in the treatment of ASD. LEVEL OF EVIDENCE: Level IV.
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2. Antoine MW, Langberg T, Schnepel P, Feldman DE. {{Increased Excitation-Inhibition Ratio Stabilizes Synapse and Circuit Excitability in Four Autism Mouse Models}}. {Neuron}. 2019.
Distinct genetic forms of autism are hypothesized to share a common increase in excitation-inhibition (E-I) ratio in cerebral cortex, causing hyperexcitability and excess spiking. We provide a systematic test of this hypothesis across 4 mouse models (Fmr1(-/y), Cntnap2(-/-), 16p11.2(del/+), Tsc2(+/-)), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reduction in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization, and spontaneous spiking were largely normal. Modeling revealed that E and I conductance changes in each mutant were quantitatively matched to yield stable, not increased, synaptic depolarization for cells near spike threshold. Correspondingly, whisker-evoked spiking was not increased in vivo despite detectably reduced inhibition. Thus, elevated E-I ratio is a common circuit phenotype but appears to reflect homeostatic stabilization of synaptic drive rather than driving network hyperexcitability in autism.
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3. Bachmann SO, Sledziowska M, Cross E, Kalbassi S, Waldron S, Chen F, Ranson A, Baudouin SJ. {{Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders}}. {Translational psychiatry}. 2019; 9(1): 29.
Deletions in the 15q11.2 region of the human genome are associated with neurobehavioral deficits, and motor development delay, as well as in some cases, symptoms of autism or schizophrenia. The cytoplasmic FMRP-interacting protein 1 (CYFIP1) is one of the four genes contained within this locus and has been associated with other genetic forms of autism spectrum disorders (ASD). In mice, Cyfip1 haploinsufficiency leads to alteration of dendritic spine morphology and defects in synaptic plasticity, two pathophysiological hallmarks of mouse models of ASD. At the behavioral level, however, Cyfip1 haploinsufficiency leads to minor phenotypes, not directly relevant for 15q11.2 deletion syndrome or ASD. A fundamental question is whether neuronal phenotypes caused by the mutation of Cyfip1 are relevant for the human condition. Here, we describe a synaptic cluster of ASD-associated proteins centered on CYFIP1 and the adhesion protein Neuroligin-3. Cyfip1 haploinsufficiency in mice led to decreased dendritic spine density and stability associated with social behavior and motor learning phenotypes. Behavioral training early in development resulted in alleviating the motor learning deficits caused by Cyfip1 haploinsufficiency. Altogether, these data provide new insight into the neuronal and behavioral phenotypes caused by Cyfip1 mutation and proof-of-concept for the development of a behavioral therapy to treat phenotypes associated with 15q11.2 syndromes and ASD.
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4. de Diego-Otero Y, Salgado-Cacho JM. {{Early detection in autism spectrum disorders}}. {Medicina clinica}. 2019.
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5. Dimond D, Schuetze M, R ES, Dhollander T, Cho I, Vinette S, Ten Eycke K, Lebel C, McCrimmon A, Dewey D, Connelly A, Bray S. {{Reduced White Matter Fiber Density in Autism Spectrum Disorder}}. {Cereb Cortex}. 2019.
Differences in brain networks and underlying white matter abnormalities have been suggested to underlie symptoms of autism spectrum disorder (ASD). However, robustly characterizing microstructural white matter differences has been challenging. In the present study, we applied an analytic technique that calculates structural metrics specific to differently-oriented fiber bundles within a voxel, termed « fixels ». Fixel-based analyses were used to compare diffusion-weighted magnetic resonance imaging data from 25 individuals with ASD (mean age = 16.8 years) and 27 typically developing age-matched controls (mean age = 16.9 years). Group comparisons of fiber density (FD) and bundle morphology were run on a fixel-wise, tract-wise, and global white matter (GWM) basis. We found that individuals with ASD had reduced FD, suggestive of decreased axonal count, in several major white matter tracts, including the corpus callosum (CC), bilateral inferior frontal-occipital fasciculus, right arcuate fasciculus, and right uncinate fasciculus, as well as a GWM reduction. Secondary analyses assessed associations with social impairment in participants with ASD, and showed that lower FD in the splenium of the CC was associated with greater social impairment. Our findings suggest that reduced FD could be the primary microstructural white matter abnormality in ASD.
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6. Dissanayake C, Searles J, Barbaro J, Sadka N, Lawson LP. {{Cognitive and behavioral differences in toddlers with autism spectrum disorder from multiplex and simplex families}}. {Autism Res}. 2019.
Prospective, longitudinal designs utilizing « high-risk » infant siblings of children diagnosed with Autism Spectrum Disorder (ASD-sibs) have provided unique and valuable insights regarding the early ASD phenotype. However, it remains unclear whether these cases are representative of all children with ASD. The objective in the present study was to investigate whether the early development of toddlers with ASD from multiplex (MPX) families, who have an affected older sibling, is similar or different to toddlers with ASD from simplex (SPX) families, where there is no affected sibling. A further aim was to examine patterns of association between autism symptom severity and cognitive functioning within each group to inform possible mechanisms for group similarities/differences. Behavioral and cognitive assessment data from a sample of toddlers with ASD was utilized, comprising 45 MPX, 127 first-born SPX, and 72 later-born SPX toddlers. Participants in the MPX group had significantly higher developmental quotients on the Mullen Scales of Early Learning compared to those in the SPX groups, who did not differ from each other. However, all three groups were similar on their autism severity scores (measured using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview), and the pattern of relationships between cognitive ability and autism symptom severity. The results suggest that caution be exercised in generalizing findings from ASD-sib samples to other samples of children with ASD. The higher cognitive abilities in the MPX group, in addition to biological differences, may also be an outcome of family environmental factors, which deserves further investigation. Autism Research 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We sought to establish whether toddlers with autism from families where there is more than one affected child, called multiplex families, are different to children from simplex families, where there is only one affected child, and no other members within the immediate family with an autism diagnosis. We found that while toddlers from multiplex families were similar to those from simplex families in their autism symptoms, they were more developmentally advanced than children in the latter group.
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7. Frizzell W, Howard L, Norris HC, Chien J. {{Homicidal Ideation and Individuals on the Autism Spectrum}}. {Journal of forensic sciences}. 2019.
Interest in the relationship between autism and violence has increased in recent years; however, no link has clearly been established between them. Researchers remain curious if autistic people with certain traits (e.g., a history of trauma) are at greater risk of violence than those individuals with autism alone. In this article, we detail two individuals with homicidal ideation (HI) admitted to inpatient psychiatric units who were found to have a diagnosis of autism without language impairment. These cases illustrate the need for mental health providers to consider autism in their differential diagnosis when evaluating an individual with HI. Broadly, we consider how an autistic individual could be susceptible to developing HI and explore treatments specific to autistic individuals that may be helpful in such cases.
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8. Hong MP, Eckert EM, Pedapati EV, Shaffer RC, Dominick KC, Wink LK, Sweeney JA, Erickson CA. {{Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study}}. {J Neurodev Disord}. 2019; 11(1): 1.
BACKGROUND: Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms. METHODS: Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization. RESULTS: Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC. CONCLUSIONS: These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments.
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9. Jia R, Steelman ZR, Jia HH. {{Psychometric Assessments of Three Self-Report Autism Scales (AQ, RBQ-2A, and SQ) for General Adult Populations}}. {J Autism Dev Disord}. 2019.
This study assesses the psychometric properties of three self-report measures of autistic-like tendencies in the general adult population: autistic spectrum quotient (AQ), adult repetitive behaviours questionnaire-2 (RBQ-2A), and systemizing quotient (SQ). Three rounds of development and testing using different U.S. and global samples led to three instruments that are psychometrically sound, parsimonious, and generalizable across populations. The resulting AQ-9, consisting of two factors: social communication and attention to detail, now mirrors the current dual diagnostic criteria in the DSM-5. The RBQ-2A-R has now been refined through CFA for the first time. The new SQ-7 scale also has updated content. All three refined scales demonstrate satisfactory psychometric validity and parsimony and now provide evidence of their appropriateness for empirical research.
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10. Kirby AV, Bakian AV, Zhang Y, Bilder DA, Keeshin BR, Coon H. {{A 20-year study of suicide death in a statewide autism population}}. {Autism Res}. 2019.
SCIENTIFIC SUMMARY: Growing concern about suicide risk among individuals with autism spectrum disorder (ASD) necessitates population-based research to determine rates in representative samples and to inform appropriate prevention efforts. This study used existing surveillance data in Utah to determine incidence of suicide among individuals with ASD over a 20-year period, and to characterize those who died. Between 1998 and 2017, 49 individuals with ASD died by suicide. Suicide cumulative incidence rates did not significantly differ between 1998 and 2012 across the ASD and non-ASD populations. Between 2013 and 2017, the cumulative incidence of suicide in the ASD population was 0.17%, which was significantly higher than in the non-ASD population (0.11%; P < 0.05). During this period, this difference was driven by suicide among females with ASD; suicide risk in females with ASD was over three times higher than in females without ASD (relative risk (RR): 3.42; P < 0.01). Among the individuals with ASD who died by suicide, average age at death and manner of death did not differ significantly between males and females. Ages at death by suicide ranged from 14 to 70 years (M[SD] = 32.41[15.98]). Individuals with ASD were significantly less likely to use firearms as a method of suicide (adjusted odds ratio: 0.33; P < 0.001). Study results expand understanding of suicide risk in ASD and point to the need for additional population-based research into suicide attempts and ideation, as well as exploration of additional risk factors. Findings also suggest a need for further study of female suicide risk in ASD. Autism Research 2019. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: This study examined suicide risk among individuals with autism spectrum disorder (ASD) in Utah over a 20-year period. Risk of suicide death in individuals with ASD was found to have increased over time and to be greater than in individuals without ASD between 2013 and 2017. Females with ASD were over three times as likely to die from suicide as females without ASD. Young people with ASD were at over twice the risk of suicide than young people without ASD. Individuals with ASD were less likely than others to die from firearm-related suicides. Lien vers le texte intégral (Open Access ou abonnement)
11. Leblond CS, Cliquet F, Carton C, Huguet G, Mathieu A, Kergrohen T, Buratti J, Lemiere N, Cuisset L, Bienvenu T, Boland A, Deleuze JF, Stora T, Biskupstoe R, Halling J, Andorsdottir G, Billstedt E, Gillberg C, Bourgeron T. {{Both rare and common genetic variants contribute to autism in the Faroe Islands}}. {NPJ genomic medicine}. 2019; 4: 1.
The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.
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12. So WC, Wong MK, Lam WY, Cheng CH, Ku SY, Lam KY, Huang Y, Wong WL. {{Who is a better teacher for children with autism? Comparison of learning outcomes between robot-based and human-based interventions in gestural production and recognition}}. {Res Dev Disabil}. 2019; 86: 62-75.
BACKGROUND: Individuals with autism spectrum disorder (ASD) tend to show deficits in engaging with humans. Previous findings have shown that robot-based training improves the gestural recognition and production of children with ASD. It is not known whether social robots perform better than human therapists in teaching children with ASD. AIMS: The present study aims to compare the learning outcomes in children with ASD and intellectual disabilities from robot-based intervention on gestural use to those from human-based intervention. METHODS AND PROCEDURES: Children aged six to 12 with low-functioning autism were randomly assigned to the robot group (N = 12) and human group (N = 11). In both groups, human experimenters or social robots engaged in daily life conversations and demonstrated to children 14 intransitive gestures in a highly-structured and standardized intervention protocol. OUTCOMES AND RESULTS: Children with ASD in the human group were as likely to recognize gestures and produce them accurately as those in the robot group in both training and new conversations. Their learning outcomes maintained for at least two weeks. CONCLUSIONS AND IMPLICATIONS: The social cues found in the human-based intervention might not influence gestural learning. It does not matter who serves as teaching agents when the lessons are highly structured.
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13. Wang Z, Khemani P, Schmitt LM, Lui S, Mosconi MW. {{Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers}}. {J Neurodev Disord}. 2019; 11(1): 2.
BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. RESULTS: Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. CONCLUSION: Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset.
